CLRN1

Chr 3AR

clarin 1

Also known as: RP61, USH3, USH3A

This gene encodes a transmembrane protein with an endoplasmic reticulum retention signal that functions at excitatory ribbon synapses between hair cells and cochlear ganglion cells, and likely at analogous retinal synapses. Mutations cause Usher syndrome type IIIa, which affects both hearing and vision with progressive hearing loss typically beginning in childhood or adolescence. The gene shows autosomal recessive inheritance and is highly intolerant to loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 1.802 OMIM phenotypes
Clinical SummaryCLRN1
🧬
Gene-Disease Validity (ClinGen)
Usher syndrome type 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 83 VUS of 200 total submissions
📖
GeneReview available — CLRN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.80LOEUF
pLI 0.000
Z-score -0.49
OE 1.17 (0.731.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.59Z-score
OE missense 1.15 (1.001.31)
150 obs / 130.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.17 (0.731.80)
00.351.4
Missense OE1.15 (1.001.31)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 11 / 9.4Missense obs/exp: 150 / 130.9Syn Z: 0.24

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic32
VUS83
Likely Benign55
Benign7
Conflicting5
18
Pathogenic
32
Likely Pathogenic
83
VUS
55
Likely Benign
7
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
2
5
0
18
Likely Pathogenic
23
7
2
0
32
VUS
3
59
21
0
83
Likely Benign
2
8
19
26
55
Benign
0
0
7
0
7
Conflicting
5
Total39765426200

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

View in ClinVar →

Protein Context — Lollipop Plot

CLRN1 · 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 →