TECTA

Chr 11

tectorin alpha

Also known as: DFNA12, DFNA8, DFNB21

NCBI Gene: 7007 ENSG00000109927 UniProt: O75443

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal dominant, 12

UniProtDeafness, autosomal recessive, 21

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nonsyndromic genetic hearing loss · AR · ClinGen 2018

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 21

2,796 rare PASS variants

Rare truncating (LoF)

1 in 200

326 rare PASS variants

Rare synonymous (reference)

1 in 30

1,181 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TECTA. 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 29	1 in 240
South Asian	~43k	1 in 22	1 in 340
Remaining (unassigned)	~30k	1 in 20	1 in 380
European (Finnish)	~27k	1 in 92	1 in 760
Admixed American	~22k	1 in 19	1 in 470
African / African American	~21k	1 in 20	1 in 260
East Asian	~20k	1 in 20	1 in 320
Ashkenazi Jewish	~13k	1 in 81	1 in 830
Middle Eastern	~2,884	1 in 19	1 in 290

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 23 coding exons well covered in gnomAD exomes and genomes.? see exons ↓