USH1G

Chr 17AR

USH1 protein network component sans

Also known as: ANKS4A, SANS

The protein encoded by this gene contains ankyrin domains and a PDZ-binding motif, and functions in pre-mRNA splicing regulation and as an anchoring/scaffolding protein in cochlear hair cells that is required for normal development and maintenance of hair cell bundles. Mutations cause Usher syndrome type 1G, an autosomal recessive disorder characterized by congenital profound hearing loss and progressive vision loss due to retinitis pigmentosa. The pathogenic mechanism is predicted to be gain-of-function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.092 OMIM phenotypes
Clinical SummaryUSH1G
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 209 VUS of 400 total submissions
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GeneReview available — USH1G
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
1.09LOEUF
pLI 0.000
Z-score 1.33
OE 0.62 (0.371.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.63Z-score
OE missense 0.90 (0.810.99)
280 obs / 311.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.371.09)
00.351.4
Missense OE0.90 (0.810.99)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 9 / 14.5Missense obs/exp: 280 / 311.4Syn Z: 2.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveUSH1G-related Usher syndromeLOFAR

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

DN
0.74top 25%
GOF
0.76top 25%
LOF
0.3453th %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

400 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic18
VUS209
Likely Benign111
Benign5
Conflicting18
38
Pathogenic
18
Likely Pathogenic
209
VUS
111
Likely Benign
5
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
1
13
0
38
Likely Pathogenic
15
1
2
0
18
VUS
0
171
35
3
209
Likely Benign
0
3
25
83
111
Benign
0
1
4
0
5
Conflicting
18
Total391777986399

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

View in ClinVar →

Protein Context — Lollipop Plot

USH1G · 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