CRYM Gene

Name	crystallin, mu
Description	Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Mutations in this gene have been associated with autosomal dominant non-syndromic deafness. [provided by RefSeq, Sep 2014]
Summary	{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>CRYM Function Summary</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n CRYM (μ‐crystallin) is a multifunctional cytosolic protein that plays a key role in intracellular thyroid hormone regulation as well as in amino acid metabolism. Structural and biochemical studies have revealed that CRYM binds triiodothyronine (T3) in an NADPH‐dependent manner, with ligand binding triggering conformational changes that favor a thyroid hormone–competent state, while also exhibiting ketimine reductase activity that links thyroid hormone bioavailability to the metabolism of cyclic ketimines in pathways such as the pipecolate (lysine degradation) route."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Across different tissues, CRYM is implicated in modulating the flux of T3 by sequestering the hormone in the cytoplasm, thereby enhancing both uptake and efflux processes when co‐expressed with thyroid hormone transporters"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and its in vivo disruption alters serum and tissue T3 concentrations without necessarily compromising peripheral thyroid hormone action."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the inner ear, CRYM is robustly expressed in structures critical for auditory function, and mutations that disrupt its subcellular localization have been linked to nonsyndromic deafness, suggesting its involvement in ionic homeostasis and cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In skeletal muscle, upregulation of CRYM has been observed in muscular dystrophies, and experimental inactivation studies indicate that CRYM not only regulates muscle fiber composition and metabolic properties but also influences contractile function through its modulation of thyroid hormone signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in the brain, CRYM is preferentially expressed in regions such as the striatum, where its reduced expression correlates with neurodegenerative changes in Huntington’s disease and may confer neuroprotection by mitigating the toxic effects of mutant huntingtin protein."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In cellular models, CRYM expression further sustains T3 responsiveness of key thyroid hormone–regulated genes, thereby modulating dynamic changes in pericellular hormone concentrations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, emerging evidence also implicates CRYM in the regulation of prostate cancer progression, as its expression is androgen‐regulated and inversely correlates with aggressive disease features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Together, these findings illustrate that CRYM acts as a critical modulator of thyroid hormone availability and signaling as well as of metabolic processes, with tissue‐specific roles that range from auditory function and muscle plasticity to neuronal protection and tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Franck Borel, Isma Hachi, Andres Palencia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of mouse mu-crystallin complexed with NADPH and the T3 thyroid hormone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.12726"}], "href": "https://doi.org/10.1111/febs.12726"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24467707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24467707"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "André Hallen, Arthur J L Cooper, Joanne F Jamie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/μ-Crystallin Under Physiological Conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11064-015-1590-5"}], "href": "https://doi.org/10.1007/s11064-015-1590-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25931162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25931162"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Edith C H Friesema, Jurgen Jansen, Jan-Willem Jachtenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2007-0112"}], "href": "https://doi.org/10.1210/me.2007-0112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18337592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18337592"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Satoru Suzuki, Nobuyoshi Suzuki, Jun-Ichirou Mori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "micro-Crystallin as an intracellular 3,5,3'-triiodothyronine holder in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2006-0403"}], "href": "https://doi.org/10.1210/me.2006-0403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17264173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17264173"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Satoko Abe, Toyomasa Katagiri, Akihiko Saito-Hisaminato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/345398"}], "href": "https://doi.org/10.1086/345398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12471561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12471561"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shin-Ichi Usami, Michio Wagatsuma, Hisakuni Fukuoka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The responsible genes in Japanese deafness patients and clinical application using Invader assay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Otolaryngol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/00016480701785046"}], "href": "https://doi.org/10.1080/00016480701785046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18368581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18368581"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Patrick W Reed, Andrea M Corse, Neil C Porter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Neurol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.expneurol.2007.03.009"}], "href": "https://doi.org/10.1016/j.expneurol.2007.03.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17451686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17451686"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Daiki Seko, Shizuka Ogawa, Tao-Sheng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "μ-Crystallin controls muscle function through thyroid hormone action."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.15-280933"}], "href": "https://doi.org/10.1096/fj.15-280933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26718889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26718889"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laetitia Francelle, Laurie Galvan, Marie-Claude Gaillard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease."}]}, {"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/ddu571"}], "href": "https://doi.org/10.1093/hmg/ddu571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25398949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25398949"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Keiko Takeshige, Takashi Sekido, Jun-ichirou Kitahara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic T3-binding protein modulates dynamic alteration of T3-mediated gene expression in cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1507/endocrj.ej13-0418"}], "href": "https://doi.org/10.1507/endocrj.ej13-0418"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24646676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24646676"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Osman Aksoy, Jan Pencik, Markus Hartenbach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.33332"}], "href": "https://doi.org/10.1002/ijc.33332"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33034050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33034050"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "A B Makar, K E McMartin, M Palese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Formate assay in body fluids: application in methanol poisoning."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Med (1975)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/0006-2944(75)90147-7"}], "href": "https://doi.org/10.1016/0006-2944(75"}, {"type": "t", "text": "90147-7) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "1"}], "href": "https://pubmed.ncbi.nlm.nih.gov/1"}]}]}]}
Synonyms	THBP, DFNA40
Proteins	CRYM_HUMAN
NCBI Gene ID	1428
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CRYM 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 122 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM 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 CRYM gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRYM 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 CRYM gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CRYM protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CRYM 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 CRYM gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CRYM 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 CRYM 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 CRYM 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 CRYM gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CRYM protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CRYM protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CRYM 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 CRYM 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 CRYM gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CRYM gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CRYM gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CRYM gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CRYM 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 CRYM gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CRYM gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CRYM 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 CRYM 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 CRYM gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CRYM gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CRYM protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CRYM 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 CRYM gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CRYM 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 CRYM from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CRYM gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.