STRC

protein-coding

stereocilin

Gene summary

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]

Previous symbols:

DFNB16

MANE transcript

NM_153700.2

Inheritance

ClinVar variants

P:91U:215B:45

Top phenotype

Deafness, autosomal recessive 16

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr15:43,599,563-43,618,800

External References & Databases

Ensembl (ENSG00000242866)

Transcript & Mutation Effects

hg38 • Region Span ~19.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive nonsyndromic hearing loss 16STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011364

Submitter: Labcorp Genetics (formerly Invitae)

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: ClinGen

The STRC gene has been associated with autosomal recessive non syndromic hearing loss (ARNSHL) in (at least) 7 probands in 3 publications. 8 unique variants (missense, nonsense, frameshift, large deletion) have been reported in humans, and variants in this gene segregated with disease in # additional family members. STRC was first associated with this disease in humans in 2001 (Verpy et al.). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is homozygous loss of function that leads to dysfunction or lack of function of the stereocilia in the inner ear. This gene-disease association is supported by a knockout mouse model designed by Verpy et al. 2008 as well as expression studies showing localization of the stereocilin protein in the inner ear. It is important to note that STRC is in close proximity with the CATSPER gene which has been found to be crucial to sperm viability and therefore large deletions of the region encompassing STRC and CATSPER2 have been shown to cause hearing loss as well as male infertility (See genereviews Hildebrand 2017 PMID: 20301780). In summary, STRC is definitively associated with ARNSHL. This has been repeatedly demonstrated in clinical diagnostic settings and has been upheld over time.

autosomal recessive nonsyndromic hearing loss 16STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011364

Submitter: PanelApp Australia

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 16AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 9429146; 10090914; 11687802; 21686705; 19246478

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STRC variants in ClinVar

14 Conditions Cataloged

Inborn genetic diseasesTotal: 134

STRC-related disorderTotal: 113

not providedTotal: 110

not specifiedTotal: 87

Autosomal recessive nonsyndromic hearing loss 16Total: 78

Rare genetic deafnessTotal: 27

Deafness-infertility syndromeTotal: 12

Spermatogenic failure 7Total: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153700.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	1 clinvar	26 clinvar	2 clinvar	30
missense		18 clinvar	210 clinvar	16 clinvar	1 clinvar	245
nonsense	21 clinvar	13 clinvar	1 clinvar			35
start loss			1 clinvar			1
frameshift	11 clinvar	16 clinvar				27
splice donor/acceptor (+/-2bp)	3 clinvar	8 clinvar	2 clinvar			13
Total	35	56	215	42	3	351

Highest pathogenic variant AF is 0.0008405896

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153700.2	RefSeq	NP_714544.1	29	MANE Select
ENST00000450892.7	Ensembl	ENSP00000401513.2	29	MANE Select
ENST00000428650.5	Ensembl	ENSP00000415991.1	10	Standard
ENST00000432436.1	Ensembl	ENSP00000407303.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell-matrix adhesion
detection of mechanical stimulus involved in sensory perception of sound
auditory receptor cell stereocilium organization

Cellular Component

cell surface
stereocilium tip
kinocilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000450892
Coding exons: 29
Length: 118863
Individuals with no LoFs: 125552
Homozygous LoFs: 0
Heterozygous LoFs: 196
Defined: 125748
p: 0.000780

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.27	374	450	0.832	0.0000234	11026
Missense (PolyPhen)		135	173.86	0.7765		4818
Synonymous	1.71	151	180	0.838	0.00000845	3952
Loss of Function	2.23	31	47.6	0.651	0.00000273	838

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00076	0.00074	rare
Latino/Admixed American	0.00094	0.00093	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00085	0.00084	rare
South Asian	0.0013	0.0013	notable
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential to the formation of horizontal top connectors between outer hair cell stereocilia. {ECO:0000250}.;
Disease: DISEASE: Deafness, autosomal recessive, 16 (DFNB16) [MIM:603720]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:11687802}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness-infertility syndrome (DIS) [MIM:611102]: Characterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes. {ECO:0000269|PubMed:17098888}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.109

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High