SEC63 Gene

HGNC Family	Heat shock proteins
Name	SEC63 homolog (S. cerevisiae)
Description	The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC62 protein are found to be associated with ribosome-free SEC61 complex. It is speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER. The Sec61-Sec62-Sec63 complex might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome-dependent degradation pathway. The encoded protein is an integral membrane protein located in the rough ER. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEC63 is emerging as a critical component in maintaining endoplasmic reticulum (ER) function and cellular homeostasis, with its dysfunction being linked to autosomal dominant polycystic liver disease (PCLD). Mutations in SEC63 disrupt the protein translocation machinery and cotranslational processing in the ER, thereby compromising protein quality control and epithelial organization. Multiple genetic studies have identified pathogenic SEC63 variants in PCLD patients, and evidence suggests that a “second-hit” somatic mutation mechanism may promote cyst formation. Furthermore, immunohistochemical analyses reveal that SEC63 is uniformly expressed in cyst epithelia, supporting a distinct role separate from other ER proteins such as hepatocystin, and implicating its interplay with components involved in ciliogenesis and Wnt signaling in the liver."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in cystogenesis, SEC63 functions as a regulatory subunit of the ER translocon machinery. It participates in the cotranslational import of nascent precursor proteins by associating with the Sec61 channel, where it facilitates substrate‐specific translocation of proteins with slowly gating signal peptides. Studies using gene silencing approaches in human cells demonstrate that SEC63 is essential for the efficient early phase of polypeptide translocation into the ER, particularly impacting the biogenesis of multi-spanning membrane proteins while remaining dispensable for tail-anchored protein integration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSEC63 also plays an important role in modulating ER stress responses. By recruiting the ATPase BiP through its luminal J-domain, SEC63 helps to temper the activity of ER stress sensors such as IRE1α. This regulatory interaction limits higher-order oligomerization and persistent RNase activity of IRE1α during prolonged stress, thus contributing to the controlled resolution of the unfolded protein response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical functions in protein translocation and stress regulation, SEC63 appears to interface with diverse cellular pathways. For example, protein interaction studies have linked SEC63 with nucleoredoxin, suggesting cross-talk with Wnt signaling cascades. Moreover, SEC63-mediated metabolic remodeling may contribute to tumor progression in hepatocellular carcinoma, and integrative genomic analyses have implicated SEC63 as a candidate factor in spontaneous preterm birth. These findings highlight the multifaceted roles of SEC63 not only in ER physiology but also in broader aspects of cellular signaling and disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sonia Davila, Laszlo Furu, Ali G Gharavi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SEC63 cause autosomal dominant polycystic liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1357"}], "href": "https://doi.org/10.1038/ng1357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15133510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15133510"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Esmé Waanders, René H M te Morsche, Rob A de Man, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extensive mutational analysis of PRKCSH and SEC63 broadens the spectrum of polycystic liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.9441"}], "href": "https://doi.org/10.1002/humu.9441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16835903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16835903"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "E Waanders, H Venselaar, R H M te Morsche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2009.01353.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2009.01353.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20095989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20095989"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Manoe J Janssen, Jody Salomon, René H M Te Morsche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of heterozygosity is present in SEC63 germline carriers with polycystic liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0050324"}], "href": "https://doi.org/10.1371/journal.pone.0050324"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23209713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23209713"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Esmé Waanders, Huib J E Croes, Cathy N Maass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cysts of PRKCSH mutated polycystic liver disease patients lack hepatocystin but express Sec63p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-008-0381-3"}], "href": "https://doi.org/10.1007/s00418-008-0381-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18224332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18224332"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Johanna M Huusko, Heli Tiensuu, Antti M Haapalainen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-96374-9"}], "href": "https://doi.org/10.1038/s41598-021-96374-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34429451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34429451"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sven Lang, Julia Benedix, Sorin V Fedeles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.096727"}], "href": "https://doi.org/10.1242/jcs.096727"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22375059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22375059"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Stefan Schorr, Duy Nguyen, Sarah Haßdenteufel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of signal peptide features for substrate specificity in human Sec62/Sec63-dependent ER protein import."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.15274"}], "href": "https://doi.org/10.1111/febs.15274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32133789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32133789"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Andreas Mades, Katherina Gotthardt, Karin Awe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of human sec63 in modulating the steady-state levels of multi-spanning membrane proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0049243"}], "href": "https://doi.org/10.1371/journal.pone.0049243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23166619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23166619"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xia Li, Sha Sun, Suhila Appathurai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Molecular Mechanism for Turning Off IRE1α Signaling during Endoplasmic Reticulum Stress."}]}, {"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.2020.108563"}], "href": "https://doi.org/10.1016/j.celrep.2020.108563"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33378667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33378667"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Linda Müller, Yosuke Funato, Hiroaki Miki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An interaction between human Sec63 and nucleoredoxin may provide the missing link between the SEC63 gene and polycystic liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2011.01.024"}], "href": "https://doi.org/10.1016/j.febslet.2011.01.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21251912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21251912"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chenyu Hu, Zechang Xin, Xiaoyan Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of ACLY by SEC63 deploys metabolic reprogramming to facilitate hepatocellular carcinoma metastasis upon endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-023-02656-7"}], "href": "https://doi.org/10.1186/s13046-023-02656-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37122003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37122003"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Edgar S Wills, René H M Te Morsche, Jeroen van Reeuwijk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver cyst gene knockout in cholangiocytes inhibits cilium formation and Wnt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddx308"}], "href": "https://doi.org/10.1093/hmg/ddx308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28973524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28973524"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Juhong Zhang, Na Wang, Anting Xu "}, {"type": "b", "children": [{"type": "t", "text": "miR‑10b‑3p, miR‑8112 and let‑7j as potential biomarkers for autoimmune inner ear diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2019.10248"}], "href": "https://doi.org/10.3892/mmr.2019.10248"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31115534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31115534"}]}]}]}
Synonyms	SEC63L, PCLD2, DNAJC23, ERDJ2, PRO2507
Proteins	SEC63_HUMAN
NCBI Gene ID	11231
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SEC63 has 7,456 functional associations with biological entities spanning 8 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) extracted from 120 datasets.

Click the + buttons to view associations for SEC63 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SEC63 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SEC63 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 SEC63 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 SEC63 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 SEC63 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 SEC63 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 SEC63 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 SEC63 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 SEC63 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 SEC63 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 SEC63 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SEC63 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 SEC63 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SEC63 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SEC63 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SEC63 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 SEC63 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 SEC63 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SEC63 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SEC63 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SEC63 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SEC63 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SEC63 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SEC63 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 SEC63 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 SEC63 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SEC63 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SEC63 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SEC63 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SEC63 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 SEC63 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 SEC63 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SEC63 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 SEC63 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 SEC63 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SEC63 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 SEC63 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SEC63 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SEC63 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 SEC63 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SEC63 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.