CRYM

Chr 16AD

crystallin mu

Also known as: DFNA40, THBP

NCBI Gene: 1428ENSG00000103316UniProt: Q14894

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]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 40MIM #616357
AD
165
ClinVar variants
14
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— CRYM
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 69 VUS of 165 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.76LOEUF
pLI 0.026
Z-score 2.21
OE 0.36 (0.19–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.98Z-score
OE missense 0.79 (0.69–0.91)
138 obs / 174.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.19–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 5 / 13.9Missense obs/exp: 138 / 174.6Syn Z: 0.89

ClinVar Variant Classifications

165 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS69
Likely Benign43
Benign28
Conflicting11
14
Pathogenic
69
VUS
43
Likely Benign
28
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
2
51
16
0
69
Likely Benign
0
3
21
19
43
Benign
0
0
26
2
28
Conflicting
—11
Total2547721165

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CRYM · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CRYSTALLIN, MU; CRYM
MIM #123740 · *

Deafness, autosomal dominant 40

MIM #616357

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
LncRNA CRYM-AS1 Inhibits Gastric Cancer Progression via Epigenetically Regulating CRYM.
Zhang P et al.·Ann Clin Lab Sci
2022
Increase in cathepsin K gene expression in Duchenne muscular dystrophy skeletal muscle.
Kimura S et al.·Neuropathology
2024Case report
Genetics of crystallins: cataract and beyond.
Graw J·Exp Eye Res
2009Review
Lysine metabolism in mammalian brain: an update on the importance of recent discoveries.
Hallen A et al.·Amino Acids
2013Review
The responsible genes in Japanese deafness patients and clinical application using Invader assay.
Usami S et al.·Acta Otolaryngol
2008Review
Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.
Mandaviya PR et al.·PLoS One
2017Meta-analysis
Identification of differential expressed lncRNAs in human thyroid cancer by a genome-wide analyses.
Lu W et al.·Cancer Med
2018
Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility?
Giagulli VA et al.·J Assist Reprod Genet
2014
Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer.
Reddy RB et al.·PLoS One
2016Meta-analysis
Gene screening facilitates diagnosis of complicated symptoms: A case report.
Duan H et al.·Mol Med Rep
2017Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools