TECTA

protein-coding

tectorin alpha

Gene summary

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]

Previous symbols:

DFNA12
DFNA8
DFNB21

MANE transcript

NM_005422.4

Inheritance

AD, AR

ClinVar variants

P:136U:779B:324

Top phenotype

Deafness, autosomal recessive 21; Deafness, autosomal dominant 12

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr11:121,101,243-121,191,490

External References & Databases

Ensembl (ENSG00000109927)

Transcript & Mutation Effects

hg38 • Region Span ~90.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019497

Submitter: ClinGen

The TECTA gene has been associated with autosomal dominant nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 12/28/17. This association was made using case-level data. At least 18 variants (missense, splice site) have been reported in humans. TECTA was first associated with this disease in humans as early as 1998 (Verhoeven et al.). Association is seen in at least 15 probands in 4 publications (9590290, 15319541, 25719458, 21520338). Variants in this gene segregated with disease in 25 additional family members. This gene-disease association is supported by multiple knock-in mouse models with variants reported in humans, as well as relevant expression studies. Of note, loss of function variants in this gene have been implicated in autosomal recessive nonsyndromic hearing loss. This has been assessed separately. In summary, missense variants in TECTA are definitively associated with autosomal dominant nonsyndromic hearing loss. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Working Group on 1/2/18.

autosomal dominant nonsyndromic hearing loss 12STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011102

Submitter: Labcorp Genetics (formerly Invitae)

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: G2P

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

autosomal dominant nonsyndromic hearing lossSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: Orphanet

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: ClinGen

The TECTA gene has been associated with autosomal recessive nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 10/11/17. This association was made using case-level data. At least 6 variants (nonsense, frameshift, splice-site) have been reported in humans. TECTA was first associated with this disease in humans as early as 1999 (Mustapha et al.). Association is seen in at least 6 probands in 5 publications (9949200, 12746400, 18022253, 18022253, 28012541). Variants in this gene segregated with disease in 27 additional family members. This gene-disease association is supported by a mouse model, a zebrafish model, and relevant expression studies. More evidence is available in the literature, but the maximum score for genetic evidence and experimental evidence has been reached. Of note, this gene has also been implicated in autosomal dominant nonsyndromic hearing loss. This has been assessed separately. In summary, TECTA is definitively associated with autosomal recessive nonsyndromic hearing loss. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Working Group on 1/2/18.

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019497

Submitter: G2P

autosomal recessive nonsyndromic hearing loss 21STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011351

Submitter: PanelApp Australia

autosomal dominant nonsyndromic hearing loss 12STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011102

Submitter: PanelApp Australia

autosomal recessive nonsyndromic hearing loss 21STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011351

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 21; Deafness, autosomal dominant 12AD/AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

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

Refs: 9150164; 9718342; 9763681; 10987647; 9590290; 9949200; 11333869; 12746400; 17661817; 17431902; 23226338

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TECTA variants in ClinVar

20 Conditions Cataloged

not providedTotal: 943

Inborn genetic diseasesTotal: 330

Autosomal dominant nonsyndromic hearing loss 12Total: 220

not specifiedTotal: 212

Autosomal recessive nonsyndromic hearing loss 21Total: 206

TECTA-related disorderTotal: 66

Hearing impairmentTotal: 17

Nonsyndromic genetic hearing lossTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005422.4. 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	2 clinvar	36 clinvar	215 clinvar	4 clinvar	258
missense	5 clinvar	29 clinvar	739 clinvar	101 clinvar	4 clinvar	878
nonsense	18 clinvar	19 clinvar	2 clinvar			39
start loss						0
frameshift	25 clinvar	25 clinvar				50
splice donor/acceptor (+/-2bp)	4 clinvar	8 clinvar	2 clinvar			14
Total	53	83	779	316	8	1239

Highest pathogenic variant AF is 0.00017886198

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005422.4	RefSeq	NP_005413.2	23	MANE Select
ENST00000392793.6	Ensembl	ENSP00000376543.1	23	MANE Select
ENST00000264037.2	Ensembl	ENSP00000264037.2	23	Standard
ENST00000642222.1	Ensembl	ENSP00000493855.1	23	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tecta	Danio rerio	Structure: otolith Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

tecta

Danio rerio

Structure: otolith

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational modification: synthesis of GPI-anchored proteins
Post-translational protein modification
Metabolism of proteins

Biological Process

cell-matrix adhesion
sensory perception of sound

Molecular Function

extracellular matrix structural constituent

Cellular Component

extracellular region
plasma membrane
anchored component of membrane
collagen-containing extracellular matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392793
Coding exons: 23
Length: 90321
Individuals with no LoFs: 125599
Homozygous LoFs: 1
Heterozygous LoFs: 148
Defined: 125748
p: 0.000593

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.61	1095	1.26e+3	0.872	0.0000817	14244
Missense (PolyPhen)		344	454.81	0.75636		5097
Synonymous	0.182	538	543	0.990	0.0000420	4146
Loss of Function	4.98	43	95.6	0.450	0.00000531	1060

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.00089	0.00089	rare
East Asian	0.00087	0.00087	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00069	0.00069	rare
South Asian	0.00052	0.00049	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: One of the major non-collagenous components of the tectorial membrane (By similarity). The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and 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. {ECO:0000250}.;
Disease: DISEASE: Deafness, autosomal dominant, 12 (DFNA12) [MIM:601543]: 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:10196713, ECO:0000269|PubMed:10987647, ECO:0000269|PubMed:12162770, ECO:0000269|PubMed:15319541, ECO:0000269|PubMed:16718611, ECO:0000269|PubMed:17661817, ECO:0000269|PubMed:20947814, ECO:0000269|PubMed:21520338, ECO:0000269|PubMed:9590290}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 21 (DFNB21) [MIM:603629]: 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:12746400, ECO:0000269|PubMed:9949200}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.207

Intolerance Scores

LoFtool: 0.229
RVIS EVS: -2.43
RVIS percentile EVS: 1.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.154

Gene Damage Prediction

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