TECTA

Chr 11ADAR

tectorin alpha

Also known as: DFNA12, DFNA8, DFNB21

NCBI Gene: 7007 ENSG00000109927 UniProt: O75443 OMIM: 602574

Alpha-tectorin is a major non-collagenous component of the tectorial membrane, an extracellular matrix in the inner ear that contacts hair cell stereocilia and enables sound transduction into electrical signals. Mutations cause both autosomal dominant and autosomal recessive forms of nonsyndromic sensorineural hearing loss, with the recessive form typically presenting as pre-lingual deafness. The gene is highly constrained against loss-of-function variants, reflecting its essential role in auditory function.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.582 OMIM phenotypes

Clinical Summary— TECTA

🧬

Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

128 unique Pathogenic / Likely Pathogenic· 771 VUS of 1424 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — TECTA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.000

Z-score 4.98

OE 0.45 (0.35–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.61Z-score

OE missense 0.87 (0.83–0.92)

1095 obs / 1255.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.35–0.58)

0≤0.351.4

Missense OE?0.87 (0.83–0.92)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 43 / 95.6Missense obs/exp: 1095 / 1255.1Syn Z: 0.18

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTECTA-related deafnessLOFAR

definitiveTECTA-related deafnessOTHERAD

This gene — mechanism propensity

0.6743th %ile

GOF

0.6736th %ile

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation

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.

Literature Evidence

DNThe mutations in the zona pellucida domain of a-tectorin may have dominant-negative phenotypes that disrupt the interactions between the different tectorin polypeptides, and as a consequence, disrupt the structure of the tectorial membrane.1

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

References

1.PMID 9590290 ↗

ClinVar Variant Classifications

1424 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54

Likely Pathogenic74

VUS771

Likely Benign292

Benign76

Conflicting144

Pathogenic

Likely Pathogenic

771

VUS

292

Likely Benign

Benign

144

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	47	6	0	1	54
Likely Pathogenic	48	22	2	2	74
VUS	2	715	21	33	771
Likely Benign	0	27	88	177	292
Benign	0	4	64	8	76
Conflicting	—				144
Total	97	774	175	221	1,411

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap TECTA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →