CAPN5 Gene

HGNC Family C2 domain containing
Name calpain 5
Description Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCalpain‐5, encoded by CAPN5, is a calcium‐dependent cysteine protease that is highly expressed in retinal photoreceptor cells. Mutations in CAPN5 have been causally linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a severe autoimmune eye disease characterized by progressive uveitis, retinal degeneration, neovascularization, and intraocular fibrosis. Structural modeling and biochemical studies have shown that disease‐causing missense mutations often reside within calcium‐sensitive flexible gating loops near the active site, causing mislocalization from the cell membrane and abnormally enhanced proteolytic activity even at low calcium levels. Animal models expressing mutant CAPN5 recapitulate many clinical, histological, and molecular features of ADNIV, thereby providing insights into aberrant retinal signaling and inflammatory responses in the diseased eye."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in retinal health, CAPN5 is emerging as a multifunctional protease with implications in diverse tissues and disease processes. In hepatocytes, for example, calpain-5 associates with the tetraspanin CD81 and other host factors to facilitate a post-binding, pre-replication entry step for hepatitis C virus, underscoring its involvement in viral invasion. In reproductive tissues, CAPN5 expression is regulated by transcription factors such as HOXA10; diminished CAPN5 levels have been observed in endometriosis, and genetic studies have associated CAPN5 variants with conditions including polycystic ovary syndrome, obesity, type 2 diabetes, and even certain thyroid carcinomas. These findings highlight the protease’s pleiotropic roles extending well beyond the retina."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, CAPN5 exhibits tightly regulated calcium-dependent autoproteolytic activation and a distinct structural organization compared to classical calpains. High-resolution crystallographic and SAXS studies reveal that CAPN5 possesses elongated, flexible loops that modulate substrate access to its catalytic groove, a feature that is further perturbed by disease-associated mutations. Notably, CAPN5 not only localizes to the cytosol and plasma membranes but is also found in mitochondria, where its activation during endoplasmic reticulum stress leads to the cleavage of caspase-4 and initiation of inflammatory cascades. Importantly, genetic approaches—including photoreceptor-specific knockout models and shRNA-mediated suppression—demonstrate that loss of CAPN5 function is well tolerated, thereby supporting the feasibility of targeted inhibition as a therapeutic strategy for hyperactive disease alleles. Emerging evidence also implicates CAPN5 in neuronal functions and ischemia-reperfusion injury, emphasizing its broader significance as a mediator of cellular homeostasis under stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vinit B Mahajan, Jessica M Skeie, Alexander G Bassuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calpain-5 mutations cause autoimmune uveitis, retinal neovascularization, and photoreceptor degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1003001"}], "href": "https://doi.org/10.1371/journal.pgen.1003001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23055945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23055945"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katherine J Wert, Jessica M Skeie, Alexander G Bassuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional validation of a human CAPN5 exome variant by lentiviral transduction into mouse retina."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt661"}], "href": "https://doi.org/10.1093/hmg/ddt661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24381307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24381307"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alexander G Bassuk, Steven Yeh, Shu Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural modeling of a novel CAPN5 mutation that causes uveitis and neovascular retinal detachment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0122352"}], "href": "https://doi.org/10.1371/journal.pone.0122352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25856303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25856303"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Katherine J Wert, Alexander G Bassuk, Wen-Hsuan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv189"}], "href": "https://doi.org/10.1093/hmg/ddv189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25994508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25994508"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gabriel Velez, Alexander G Bassuk, Kellie A Schaefer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel de novo "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CAPN5"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutation in a patient with inflammatory vitreoretinopathy, hearing loss, and developmental delay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cold Spring Harb Mol Case Stud (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/mcs.a002519"}], "href": "https://doi.org/10.1101/mcs.a002519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29472286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29472286"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yan Wang, Heming Li, Shihu Zang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Photoreceptor Cell-Derived CAPN5 Regulates Retinal Pigment Epithelium Cell Proliferation Through Direct Regulation of SLIT2 Cleavage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.17-22689"}], "href": "https://doi.org/10.1167/iovs.17-22689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29610848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29610848"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gabriel Velez, Jing Yang, Angela S Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-44031-7"}], "href": "https://doi.org/10.1038/s41598-019-44031-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31110225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31110225"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Angela S Li, Gabriel Velez, Benjamin Darbro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-Exome Sequencing of Patients With Posterior Segment Uveitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Ophthalmol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajo.2020.07.021"}], "href": "https://doi.org/10.1016/j.ajo.2020.07.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32707200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32707200"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Feng-Jie Xia, Jiao Lyu, Xiang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early-onset Neovascular Inflammatory Vitreoretinopathy Due to Two de Novo CAPN5 Mutations in Chinese Patients: A Case Series."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ocul Immunol Inflamm (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/09273948.2022.2110901"}], "href": "https://doi.org/10.1080/09273948.2022.2110901"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36369866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36369866"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "A González, M E Sáez, M J Aragón, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific haplotypes of the CALPAIN-5 gene are associated with polycystic ovary syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dei443"}], "href": "https://doi.org/10.1093/humrep/dei443"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16396936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16396936"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "María E Sáez, María T Martínez-Larrad, Reposo Ramírez-Lorca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2350-8-1"}], "href": "https://doi.org/10.1186/1471-2350-8-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17227582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17227582"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "María E Sáez, Antonio Grilo, Francisco J Morón, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Diabetol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1475-2840-7-23"}], "href": "https://doi.org/10.1186/1475-2840-7-23"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18657264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18657264"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "M Hidalgo, M E Saez, F J Martinez-Tello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of allelic imbalance involving EMSY, CAPN5, and PAK1 genes in papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol Invest (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/BF03345613"}], "href": "https://doi.org/10.1007/BF03345613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18787380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18787380"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Ivan Penna, Hongling Du, Rui Ferriani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gan055"}], "href": "https://doi.org/10.1093/molehr/gan055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18829447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18829447"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Janina Bruening, Lisa Lasswitz, Pia Banse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1007111"}], "href": "https://doi.org/10.1371/journal.ppat.1007111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30024968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30024968"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Anuradhaa Waghray, Deng-shun Wang, Deborah McKinsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning and characterization of rat and human calpain-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.09.012"}], "href": "https://doi.org/10.1016/j.bbrc.2004.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15464980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15464980"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Nnamdi G Nelson, Jessica M Skeie, Hakim Muradov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CAPN5 gene silencing by short hairpin RNA interference."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Res Notes (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1756-0500-7-642"}], "href": "https://doi.org/10.1186/1756-0500-7-642"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25216694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25216694"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Kellie A Schaefer, Marcus A Toral, Gabriel Velez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.15-18680"}], "href": "https://doi.org/10.1167/iovs.15-18680"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27152965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27152965"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Lokesh Gakhar, Alexander G Bassuk, Gabriel Velez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small-angle X-ray scattering of calpain-5 reveals a highly open conformation among calpains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Struct Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jsb.2016.07.017"}], "href": "https://doi.org/10.1016/j.jsb.2016.07.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27474374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27474374"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Cagney E Coomer, Ann C Morris "}, {"type": "b", "children": [{"type": "t", "text": "Capn5 Expression in the Healthy and Regenerating Zebrafish Retina."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.18-24278"}], "href": "https://doi.org/10.1167/iovs.18-24278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30029251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30029251"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Katherine J Wert, Susanne F Koch, Gabriel Velez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23894"}], "href": "https://doi.org/10.1002/humu.23894"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31403230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31403230"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Gabriel Velez, Young Joo Sun, Saif Khan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Insights into the Unique Activation Mechanisms of a Non-classical Calpain and Its Disease-Causing Variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.12.077"}], "href": "https://doi.org/10.1016/j.celrep.2019.12.077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31968260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31968260"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Yusaku Chukai, Takeshi Iwamoto, Ken Itoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of mitochondrial calpain-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2021.118989"}], "href": "https://doi.org/10.1016/j.bbamcr.2021.118989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33607190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33607190"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Yusaku Chukai, Ginga Ito, Masahide Konno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial calpain-5 truncates caspase-4 during endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2022.03.156"}], "href": "https://doi.org/10.1016/j.bbrc.2022.03.156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35398613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35398613"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Yusaku Chukai, Ginga Ito, Yasuo Miki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of calpain-5 in cerebral ischemia and reperfusion injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gen Subj (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2023.130506"}], "href": "https://doi.org/10.1016/j.bbagen.2023.130506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37949151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37949151"}]}]}]}
Synonyms HTRA3, ADNIV, VRNI, NCL-3
Proteins CAN5_HUMAN
NCBI Gene ID 726
API
Download Associations
Predicted Functions View CAPN5's ARCHS4 Predicted Functions.
Co-expressed Genes View CAPN5's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CAPN5's ARCHS4 Predicted Functions.

Functional Associations

CAPN5 has 6,533 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for CAPN5 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Achilles Cell Line Gene Essentiality Profiles cell lines with fitness changed by CAPN5 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of CAPN5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of CAPN5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of CAPN5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of CAPN5 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CAPN5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CAPN5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of CAPN5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of CAPN5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of CAPN5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with CAPN5 protein from the CCLE Cell Line Proteomics dataset.
CellMarker Gene-Cell Type Associations cell types associated with CAPN5 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CAPN5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of CAPN5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of CAPN5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
ClinVar Gene-Phenotype Associations phenotypes associated with CAPN5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
ClinVar Gene-Phenotype Associations 2025 phenotypes associated with CAPN5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CAPN5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing CAPN5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing CAPN5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing CAPN5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing CAPN5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with CAPN5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with CAPN5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of CAPN5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with CAPN5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with CAPN5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with CAPN5 gene/protein from the curated CTD Gene-Disease Associations dataset.
DeepCoverMOA Drug Mechanisms of Action small molecule perturbations with high or low expression of CAPN5 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by CAPN5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with CAPN5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CAPN5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with CAPN5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with CAPN5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CAPN5 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CAPN5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of CAPN5 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing CAPN5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with CAPN5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with CAPN5 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of CAPN5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with CAPN5 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing CAPN5 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of CAPN5 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CAPN5 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of CAPN5 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CAPN5 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of CAPN5 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of CAPN5 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving CAPN5 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving CAPN5 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving CAPN5 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing CAPN5 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing CAPN5 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing CAPN5 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by CAPN5 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by CAPN5 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by CAPN5 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of CAPN5 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of CAPN5 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CAPN5 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with CAPN5 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with CAPN5 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Disease Associations diseases associated with CAPN5 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with CAPN5 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of CAPN5 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of CAPN5 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of CAPN5 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of CAPN5 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPO Gene-Disease Associations phenotypes associated with CAPN5 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset.
HuBMAP Azimuth Cell Type Annotations cell types associated with CAPN5 gene from the HuBMAP Azimuth Cell Type Annotations dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with CAPN5 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for CAPN5 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of CAPN5 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of CAPN5 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of CAPN5 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of CAPN5 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of CAPN5 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with CAPN5 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of CAPN5 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of CAPN5 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LOCATE Curated Protein Localization Annotations cellular components containing CAPN5 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain CAPN5 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by CAPN5 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of CAPN5 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by CAPN5 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of CAPN5 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of CAPN5 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing CAPN5 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
OMIM Gene-Disease Associations phenotypes associated with CAPN5 gene from the curated OMIM Gene-Disease Associations dataset.
PANTHER Pathways pathways involving CAPN5 protein from the PANTHER Pathways dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for CAPN5 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CAPN5 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of CAPN5 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving CAPN5 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving CAPN5 protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving CAPN5 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of CAPN5 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CAPN5 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CAPN5 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CAPN5 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CAPN5 gene from the RummaGEO Gene Perturbation Signatures dataset.
Sanger Dependency Map Cancer Cell Line Proteomics cell lines associated with CAPN5 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of CAPN5 gene from the Sci-Plex Drug Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of CAPN5 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of CAPN5 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of CAPN5 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of CAPN5 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of CAPN5 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of CAPN5 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CAPN5 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of CAPN5 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CAPN5 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with CAPN5 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CAPN5 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving CAPN5 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving CAPN5 protein from the WikiPathways Pathways 2024 dataset.