USH2A

Chr 1AR

usherin

Also known as: RP39, US2, USH2, dJ1111A8.1

The USH2A protein is a basement membrane component containing laminin, pentaxin, and fibronectin domains that maintains hair bundle ankle formation in cochlear hair cells and the periciliary membrane complex in retinal photoreceptors. Mutations cause autosomal recessive Usher syndrome type 2A (progressive hearing loss with retinitis pigmentosa) and isolated retinitis pigmentosa 39. The gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.864 OMIM phenotypes
Clinical SummaryUSH2A
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Gene-Disease Validity (ClinGen)
Usher syndrome type 2 · 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.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 3.46
OE 0.76 (0.670.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-2.47Z-score
OE missense 1.13 (1.101.17)
3076 obs / 2713.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.76 (0.670.86)
00.351.4
Missense OE1.13 (1.101.17)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 178 / 235.3Missense obs/exp: 3076 / 2713.4Syn Z: -4.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveUSH2A-related Usher syndromeLOFAR

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

DN
0.6842th %ile
GOF
0.6149th %ile
LOF
0.4233th %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

USH2A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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