CRYM

crystallin mu

Basic information

Region (hg38): 16:21238874-21303083

Links

ENSG00000103316 ∙ NCBI:1428 ∙ OMIM:123740 ∙ HGNC:2418 ∙ Uniprot:Q14894 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 40 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 40 (Limited), mode of inheritance: Unknown
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 40	AD	Audiologic/Otolaryngologic	As some patients have been described with prelingual hearing loss, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	12471561

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRYM gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				16	2	18
missense			27	4		31
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	4		5
non coding			8	12	26	46
Total	0	0	37	32	28

Variants in CRYM

This is a list of pathogenic ClinVar variants found in the CRYM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-21249980-G-T		not specified	Uncertain significance (May 04, 2023)
16-21250114-C-T		not specified	Uncertain significance (Oct 10, 2023)
16-21250299-G-C		not specified	Uncertain significance (Feb 27, 2024)
16-21250407-A-G		not specified	Uncertain significance (Jun 17, 2024)
16-21250432-A-T			Uncertain significance (Jul 25, 2023)
16-21250437-A-G		not specified	Uncertain significance (Sep 14, 2022)
16-21250472-G-T		not specified	Uncertain significance (May 20, 2024)
16-21250536-G-A		not specified	Likely benign (Jan 26, 2022)
16-21250587-G-A		not specified	Uncertain significance (Aug 02, 2021)
16-21250596-G-A		not specified	Uncertain significance (Dec 18, 2023)
16-21250797-C-A		not specified	Uncertain significance (Dec 19, 2023)
16-21258668-T-C			Likely benign (Aug 06, 2018)
16-21258774-CTTTG-C		CRYM-related disorder	Likely benign (Apr 05, 2019)
16-21258781-T-A		Autosomal dominant nonsyndromic hearing loss 40	no classifications from unflagged records (Apr 25, 2024)
16-21258783-A-G		Autosomal dominant nonsyndromic hearing loss 40	Uncertain significance (Sep 26, 2019)
16-21258785-T-G		Autosomal dominant nonsyndromic hearing loss 40	Pathogenic (Jan 01, 2003)
16-21258810-T-C			Uncertain significance (Dec 31, 2022)
16-21258819-C-T		not specified • Autosomal dominant nonsyndromic hearing loss 40	Uncertain significance (Dec 30, 2022)
16-21258836-A-G		not specified	Uncertain significance (Jun 01, 2023)
16-21258841-C-A		not specified	Uncertain significance (Feb 07, 2023)
16-21258875-T-C			Likely benign (Jun 17, 2021)
16-21258960-A-C			Benign (Dec 17, 2018)
16-21260990-G-A			Benign (Dec 23, 2018)
16-21261044-T-C			Benign (Apr 09, 2019)
16-21261216-G-A			Likely benign (Oct 03, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRYM	protein_coding	protein_coding	ENST00000219599	8	64210

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0257	0.963	125618	1	129	125748	0.000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.984	138	175	0.790	0.00000889	2002
Missense in Polyphen		37	56.374	0.65633		690
Synonymous	0.894	61	70.6	0.865	0.00000370	652
Loss of Function	2.21	5	13.9	0.360	5.97e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00625	0.00620
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.000370	0.000370
European (Non-Finnish)	0.0000619	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically catalyzes the reduction of imine bonds in brain substrates that may include cystathionine ketimine (CysK) and lanthionine ketimine (LK). Binds thyroid hormone which is a strong reversible inhibitor. Presumably involved in the regulation of the free intracellular concentration of triiodothyronine and access to its nuclear receptors. {ECO:0000269|PubMed:21332720}.
• Pathway: Lysine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;lysine degradation II (pipecolate pathway) (Consensus)

Recessive Scores

• pRec: 0.233

Intolerance Scores

• loftool: 0.385
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.53

Haploinsufficiency Scores

• pHI: 0.481
• hipred: N
• hipred_score: 0.458
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.278

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Crym
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;lysine catabolic process;sensory perception of sound;thyroid hormone metabolic process;oxidation-reduction process;thyroid hormone transport
• Cellular component: nucleus;cytoplasm;mitochondrion;peroxisomal matrix;cytosol;extracellular exosome
• Molecular function: transcription corepressor activity;protein binding;oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor;hormone binding;protein homodimerization activity;thiomorpholine-carboxylate dehydrogenase activity;NADP binding;thyroid hormone binding