USH1C

Chr 11AR

USH1 protein network component harmonin

Also known as: AIE-75, DFNB18, DFNB18A, NY-CO-37, NY-CO-38, PDZ-45, PDZ-73, PDZ-73/NY-CO-38

This gene encodes a scaffold protein that anchors and organizes protein complexes essential for mechanotransduction in cochlear hair cells and microvilli organization. Mutations cause autosomal recessive Usher syndrome type 1C (congenital profound deafness with prepubertal onset retinitis pigmentosa) and isolated autosomal recessive deafness. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.893 OMIM phenotypes
Clinical SummaryUSH1C
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 2.22
OE 0.67 (0.510.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.87Z-score
OE missense 1.11 (1.031.19)
583 obs / 526.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.67 (0.510.89)
00.351.4
Missense OE1.11 (1.031.19)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 36 / 53.5Missense obs/exp: 583 / 526.6Syn Z: -1.92
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveUSH1C-related Usher syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7035th %ile
GOF
0.77top 25%
LOF
0.3454th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

USH1C · 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.

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Clinical Literature
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