PYCR2 Gene

Name	pyrroline-5-carboxylate reductase family, member 2
Description	This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPYCR2 is a mitochondrial enzyme that catalyzes the final step of L‐proline biosynthesis by reducing L‑pyrroline‑5‑carboxylate to L‑proline. Detailed biochemical and structural studies have demonstrated that PYCR2 operates via a sequential substrate binding mechanism, and that disease‐associated variants (for example, Arg119Cys and Arg251Cys) exhibit markedly impaired catalytic efficiency and compromised thermodynamic stability. This fundamental enzymatic activity highlights PYCR2’s central role in cellular metabolism and protein folding."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Disruptions in PYCR2 function also play a critical role in neurodevelopment. Loss‐of‐function mutations have been linked to severe syndromic disorders characterized by postnatal microcephaly, hypomyelination, and global developmental delay. Studies in patient‐derived cells and animal models underscore that PYCR2 deficiency leads to decreased mitochondrial membrane potential and an increased susceptibility to apoptosis under oxidative stress, thereby underpinning conditions such as hypomyelinating leukodystrophy type 10 and, in some cases, hereditary spastic paraplegia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "In the context of cellular stress response, PYCR2 is a key component of protein complexes that safeguard mitochondrial integrity. Its association with the stress‐response factor RRM2B is essential for maintaining a continuous mitochondrial network and protecting cells from oxidative damage. Indeed, experimental silencing of PYCR2 results in impaired proliferation, mitochondrial fragmentation, and an enhanced sensitivity to oxidative stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "Beyond its roles in normal metabolism and neurodevelopment, aberrant PYCR2 expression has emerged as an important contributor to oncogenesis. Increased levels of PYCR2 have been observed in a variety of malignancies—including melanoma, colon, lung, hepatocellular, and colorectal cancers—where its upregulation promotes tumorigenic processes through enhanced glycolysis and the activation of key signaling pathways such as AMPK/mTOR, AKT, and Wnt/β‑catenin. Functionally, knockdown studies indicate that reducing PYCR2 levels can curtail cellular viability, migration, invasion, and microsphere formation while inducing apoptosis, thereby positioning PYCR2 as a potential prognostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nathalie Escande-Beillard, Abigail Loh, Sahar N Saleem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2020.03.028"}], "href": "https://doi.org/10.1016/j.neuron.2020.03.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32330411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32330411"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sagar M Patel, Javier Seravalli, Xinwen Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disease variants of human Δ"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "1"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-pyrroline-5-carboxylate reductase 2 (PYCR2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2021.108852"}], "href": "https://doi.org/10.1016/j.abb.2021.108852"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33771508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33771508"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tojo Nakayama, Almundher Al-Maawali, Malak El-Quessny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2015.03.003"}], "href": "https://doi.org/10.1016/j.ajhg.2015.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25865492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25865492"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maha S Zaki, Gifty Bhat, Tipu Sultan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PYCR2 Mutations cause a lethal syndrome of microcephaly and failure to thrive."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.24678"}], "href": "https://doi.org/10.1002/ana.24678"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27130255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27130255"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chawan Manaspon, Ponghatai Boonsimma, Chureerat Phokaew, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the genotypic spectrum of PYCR2 and a common ancestry in Thai patients with hypomyelinating leukodystrophy 10."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62365"}], "href": "https://doi.org/10.1002/ajmg.a.62365"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34037307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34037307"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gunes Sager, Ayberk Türkyilmaz, Hediye Pınar Günbey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyrroline-5-carboxylate reductase 2 (PYCR2) deficiency causes hereditary spastic paraplaegia in late childhood."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Paediatr Neurol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejpn.2023.04.002"}], "href": "https://doi.org/10.1016/j.ejpn.2023.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37141741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37141741"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mei-Ling Kuo, Mabel Bin-Er Lee, Michelle Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep18846"}], "href": "https://doi.org/10.1038/srep18846"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26733354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26733354"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rongying Ou, Xueqi Zhang, Jianfeng Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of pyrroline-5-carboxylate reductase-2 induces the autophagy of melanoma cells via AMPK/mTOR pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3927-8"}], "href": "https://doi.org/10.1007/s13277-015-3927-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26634742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26634742"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sitong Wang, Linaer Gu, Lili Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.07.084"}], "href": "https://doi.org/10.1016/j.bbrc.2021.07.084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34332325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34332325"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Feng Yin, Xiaoxia Huang, Yi Xuan "}, {"type": "b", "children": [{"type": "t", "text": "Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Cancer Progression via Activating PI3K/AKT/mTOR Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Markers (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/9950663"}], "href": "https://doi.org/10.1155/2021/9950663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34512817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34512817"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yang Geng, Pengfei Chen, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA MALAT1 regulates growth of carcinoma of the lung through modulating miR-338-3p/PYCR2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol (Noisy-le-grand) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14715/cmb/2023.69.4.21"}], "href": "https://doi.org/10.14715/cmb/2023.69.4.21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37329534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37329534"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Raju Lama Tamang, Balawant Kumar, Sagar M Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells12141883"}], "href": "https://doi.org/10.3390/cells12141883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37508547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37508547"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Shaoyan Wang, Wenyan Yi, Zhenyu Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PYCR2 promotes growth and aerobic glycolysis in human liver cancer by regulating the AKT signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2023.09.007"}], "href": "https://doi.org/10.1016/j.bbrc.2023.09.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37708598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37708598"}]}]}]}
Synonyms	P5CR2, HLD10
Proteins	P5CR2_HUMAN
NCBI Gene ID	29920
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PYCR2 has 5,932 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 122 datasets.

Click the + buttons to view associations for PYCR2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PYCR2 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PYCR2 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 PYCR2 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 PYCR2 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 PYCR2 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 PYCR2 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 PYCR2 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 PYCR2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PYCR2 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 PYCR2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PYCR2 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 PYCR2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PYCR2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PYCR2 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 PYCR2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PYCR2 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 PYCR2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PYCR2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PYCR2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PYCR2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PYCR2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PYCR2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PYCR2 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 PYCR2 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 PYCR2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PYCR2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PYCR2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PYCR2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PYCR2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PYCR2 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 PYCR2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PYCR2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PYCR2 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 PYCR2 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 PYCR2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PYCR2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PYCR2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PYCR2 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 PYCR2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PYCR2 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 PYCR2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.