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…

GOFmechanismARLOEUF 0.881 OMIM phenotype

Clinical Summary— STRC

🧬

Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · 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.

📋

ClinVar Variants

79 unique Pathogenic / Likely Pathogenic· 193 VUS of 344 total submissions

Explore recent and relevant literature in Research Assistant →

📖

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

This gene — mechanism propensity

0.5968th %ile

GOF

0.6833th %ile

LOF

0.3068th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

344 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47

Likely Pathogenic32

VUS193

Likely Benign34

Benign20

Conflicting13

Pathogenic

Likely Pathogenic

193

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	31	0	16	0	47
Likely Pathogenic	24	5	3	0	32
VUS	1	177	15	0	193
Likely Benign	0	7	8	19	34
Benign	0	3	14	3	20
Conflicting	—				13
Total	56	192	56	22	339

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 56) ClinVar copy-number / structural variants overlap STRC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →