USH2A

Chr 1AR

usherin

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

This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

OMIMResearchGenerating clinical summary…
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 OE?0.76 (0.670.86)
00.351.4
Missense OE?1.13 (1.101.17)
00.61.4
Synonymous OE?1.16
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

This gene — mechanism propensity

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.