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 functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

OMIMResearchGenerating clinical summary…
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 OE?0.67 (0.510.89)
00.351.4
Missense OE?1.11 (1.031.19)
00.61.4
Synonymous OE?1.17
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

This gene — mechanism propensity

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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