CLRN2

Chr 4AR

clarin 2

Also known as: DFNB117

CLRN2 encodes clarin-2, a four-transmembrane domain protein required for normal organization and maintenance of stereocilia bundles and mechano-electrical transduction in the inner ear. Mutations cause autosomal recessive hearing loss. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismARLOEUF 1.611 OMIM phenotype
Clinical SummaryCLRN2
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 46 VUS of 97 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.61LOEUF
pLI 0.000
Z-score 0.18
OE 0.94 (0.561.61)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.26Z-score
OE missense 0.94 (0.821.08)
136 obs / 144.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.561.61)
00.351.4
Missense OE0.94 (0.821.08)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 9 / 9.6Missense obs/exp: 136 / 144.9Syn Z: -0.77
DN
0.5081th %ile
GOF
0.7029th %ile
LOF
0.2871th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

97 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic1
VUS46
Likely Benign6
Benign1
42
Pathogenic
1
Likely Pathogenic
46
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
41
0
42
Likely Pathogenic
0
0
1
0
1
VUS
0
37
9
0
46
Likely Benign
0
4
2
0
6
Benign
0
1
0
0
1
Total04353096

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

View in ClinVar →

Protein Context — Lollipop Plot

CLRN2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found