STRC

Chr 15AR

stereocilin

Also known as: DFNB16

NCBI Gene: 161497 ENSG00000242866 UniProt: Q7RTU9 OMIM: 606440

The protein is essential for formation of horizontal top connectors between outer hair cell stereocilia in the inner ear, which are critical for mechanoreception of sound waves. Mutations cause autosomal recessive non-syndromic deafness (DFNB16), typically presenting as congenital hearing loss. This gene shows extremely low constraint against loss-of-function variants in the general population and follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 16MIM #603720

UniProtDeafness-infertility syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nonsyndromic genetic hearing loss · AR · ClinGen 2017

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.88

LOEUF

GOF

Mechanism· predicted

📖

GeneReview available — STRC

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.23

OE 0.65 (0.49–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.27Z-score

OE missense 0.83 (0.76–0.91)

374 obs / 449.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.49–0.88)

0≤0.351.4

Missense OE?0.83 (0.76–0.91)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 31 / 47.6Missense obs/exp: 374 / 449.7Syn Z: 1.71

Background carrier burden — how many people carry a rare variant somewhere in STRC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

571 rare PASS variants

Rare truncating (LoF)

1 in 220

120 rare PASS variants

Rare synonymous (reference)

1 in 190

202 rare PASS variants

Rare missense and truncating variants are carried at similar rates in STRC; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 90	1 in 340
South Asian	~43k	1 in 45	1 in 250
Remaining (unassigned)	~30k	1 in 44	1 in 410
European (Finnish)	~27k	1 in 340	1 in 650
Admixed American	~22k	1 in 54	1 in 350
African / African American	~21k	1 in 45	1 in 500
East Asian	~20k	1 in 76	1 in 430
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 4,400
Middle Eastern	~2,882	1 in 81	1 in 250

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 29 coding exons well covered in gnomAD exomes; exons 1, 3, 4, 5, 6 and 10 more poorly covered; exons 2, 25 marginal. Genomes: 6 of 29 (exons 1, 2, 3, 4, 5 and 18 more below).? see exons ↓