WHRN
Chr 9ARwhirlin
Also known as: CIP98, DFNB31, PDZD7B, USH2D, WI
The protein is essential for stereocilia elongation and maintenance in inner ear hair cells and for maintaining the periciliary membrane complex in retinal photoreceptors. Mutations cause autosomal recessive nonsyndromic hearing loss (DFNB31) or Usher syndrome type 2D, which combines hearing loss with progressive vision loss due to retinitis pigmentosa. The gene is highly intolerant to loss-of-function variants (LOEUF 0.668), reflecting its critical role in sensory organ development and maintenance.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 19 | 0 | 2 | 0 | 21 |
Likely Pathogenic | 11 | 1 | 1 | 0 | 13 |
VUS | 1 | 292 | 23 | 6 | 322 |
Likely Benign | 0 | 5 | 52 | 136 | 193 |
Benign | 0 | 2 | 25 | 4 | 31 |
Conflicting | — | 11 | |||
| Total | 31 | 300 | 103 | 146 | 591 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
WHRN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools