Autosomal dominant nonsyndromic hearing loss 12

Summary

Autosomal dominant nonsyndromic hearing loss 12 (MONDO:0011102) is a disease caused by TECTA (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TECTA (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 228

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 12
Mondo ID	MONDO:0011102
MeSH	C563295
OMIM	601543
DOID	DOID:0110544
UMLS	C1832187
MedGen	321902
GARD	0018107
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 12 · autosomal dominant deafness 8 · autosomal dominant nonsyndromic deafness 12 · autosomal dominant nonsyndromic deafness caused by mutation in TECTA · autosomal dominant nonsyndromic deafness type 12 · autosomal dominant nonsyndromic hearing loss 12 · deafness, autosomal dominant 12 · deafness, autosomal dominant 8 · deafness, autosomal dominant 8/12 · deafness, autosomal dominant type 12 · DFNA12 · DFNA8 · TECTA autosomal dominant nonsyndromic deafness

Data availability: 228 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant nonsyndromic hearing loss › autosomal dominant nonsyndromic hearing loss 12

Related subtypes (75): autosomal dominant nonsyndromic hearing loss 1, autosomal dominant nonsyndromic hearing loss 2A, autosomal dominant nonsyndromic hearing loss 4A, autosomal dominant nonsyndromic hearing loss 6, autosomal dominant nonsyndromic hearing loss 5, autosomal dominant nonsyndromic hearing loss 10, autosomal dominant nonsyndromic hearing loss 11, autosomal dominant nonsyndromic hearing loss 9, autosomal dominant nonsyndromic hearing loss 7, autosomal dominant nonsyndromic hearing loss 3A, autosomal dominant nonsyndromic hearing loss 13, autosomal dominant nonsyndromic hearing loss 15, autosomal dominant nonsyndromic hearing loss 17, autosomal dominant nonsyndromic hearing loss 16, autosomal dominant nonsyndromic hearing loss 20, autosomal dominant nonsyndromic hearing loss 23, autosomal dominant nonsyndromic hearing loss 25, autosomal dominant nonsyndromic hearing loss 18, autosomal dominant nonsyndromic hearing loss 24, autosomal dominant nonsyndromic hearing loss 22, autosomal dominant nonsyndromic hearing loss 30, autosomal dominant nonsyndromic hearing loss 36, autosomal dominant nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 44, autosomal dominant nonsyndromic hearing loss 48, autosomal dominant nonsyndromic hearing loss 41, autosomal dominant nonsyndromic hearing loss 49, autosomal dominant nonsyndromic hearing loss 43, autosomal dominant nonsyndromic hearing loss 28, autosomal dominant nonsyndromic hearing loss 31, autosomal dominant nonsyndromic hearing loss 47, autosomal dominant auditory neuropathy 1, autosomal dominant nonsyndromic hearing loss 53, autosomal dominant nonsyndromic hearing loss 27, autosomal dominant nonsyndromic hearing loss 59, autosomal dominant nonsyndromic hearing loss 3B, autosomal dominant nonsyndromic hearing loss 2B, autosomal dominant nonsyndromic hearing loss 50, autosomal dominant nonsyndromic hearing loss 51, autosomal dominant nonsyndromic hearing loss 64, autosomal dominant nonsyndromic hearing loss 33, autosomal dominant nonsyndromic hearing loss 4B, autosomal dominant nonsyndromic hearing loss 56, autosomal dominant nonsyndromic hearing loss 54, autosomal dominant nonsyndromic hearing loss 58, autosomal dominant nonsyndromic hearing loss 65, autosomal dominant nonsyndromic hearing loss 67, autosomal dominant nonsyndromic hearing loss 40, autosomal dominant nonsyndromic hearing loss 69, autosomal dominant nonsyndromic hearing loss 68, autosomal dominant nonsyndromic hearing loss 70, autosomal dominant nonsyndromic hearing loss 66, hearing loss, autosomal dominant 74, hearing loss, autosomal dominant 77, hearing loss, autosomal dominant 81, hearing loss, autosomal dominant 82, hearing loss, autosomal dominant 83, hearing loss, autosomal dominant 84, hearing loss, autosomal dominant 80, hearing loss, autosomal dominant 37, hearing loss, autosomal dominant 75, hearing loss, autosomal dominant 76, hearing loss, autosomal dominant 71, hearing loss, autosomal dominant 72, hearing loss, autosomal dominant 73, hearing loss, autosomal dominant 34, with or without inflammation, hearing loss, autosomal dominant 78, hearing loss, autosomal dominant 79, hearing loss, autosomal dominant 85, hearing loss, autosomal dominant 86, hearing loss, autosomal dominant 87, hearing loss, autosomal dominant 88, hearing loss, autosomal dominant 89, hearing loss, autosomal dominant 90, autosomal dominant nonsyndromic hearing loss 91

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

228 retrieved; paginated sample, class counts are floors:

105 uncertain significance, 71 conflicting classifications of pathogenicity, 11 benign, 10 pathogenic, 10 pathogenic/likely pathogenic, 8 benign/likely benign, 7 likely pathogenic, 5 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
7013	NM_005422.2(TECTA):c.[5458C>T;5471G>A]		Pathogenic	no assertion criteria provided
236059	NM_005422.4(TECTA):c.2887G>A (p.Ala963Thr)	LOC126861365	Pathogenic	no assertion criteria provided
1185582	NM_005422.4(TECTA):c.5383+5_5383+8del	TBCEL-TECTA	Pathogenic	criteria provided, multiple submitters, no conflicts
1329694	NM_005422.4(TECTA):c.102del (p.Asn34fs)	TBCEL-TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1708127	NM_005422.4(TECTA):c.1115dup (p.Ser373fs)	TBCEL-TECTA	Pathogenic	criteria provided, single submitter
2087823	NM_005422.4(TECTA):c.1048C>T (p.Arg350Ter)	TBCEL-TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236058	NM_005422.4(TECTA):c.5597C>T (p.Thr1866Met)	TBCEL-TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601876	NM_005422.4(TECTA):c.805C>T (p.Arg269Ter)	TBCEL-TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7014	NM_005422.4(TECTA):c.5609A>G (p.Tyr1870Cys)	TBCEL-TECTA	Pathogenic	criteria provided, single submitter
7015	NM_005422.4(TECTA):c.2941+1G>A	TBCEL-TECTA	Pathogenic	criteria provided, multiple submitters, no conflicts
7016	NM_005422.4(TECTA):c.3169T>A (p.Cys1057Ser)	TBCEL-TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7017	NM_005422.4(TECTA):c.4856G>C (p.Cys1619Ser)	TBCEL-TECTA	Pathogenic	no assertion criteria provided
7022	NM_005422.4(TECTA):c.5668C>T (p.Arg1890Cys)	TBCEL-TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137273	NM_005422.4(TECTA):c.4690-1G>A	TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236033	NM_005422.4(TECTA):c.6017A>G (p.Asp2006Gly)	TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
498538	NM_005422.4(TECTA):c.4085G>A (p.Trp1362Ter)	TECTA	Pathogenic	reviewed by expert panel
7020	NM_005422.4(TECTA):c.5509T>G (p.Cys1837Gly)	TECTA	Pathogenic	no assertion criteria provided
7021	NM_005422.4(TECTA):c.6062G>A (p.Arg2021His)	TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7023	NM_005422.4(TECTA):c.5509T>C (p.Cys1837Arg)	TECTA	Pathogenic	no assertion criteria provided
930525	NM_005422.4(TECTA):c.6061C>T (p.Arg2021Cys)	TECTA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027366	NM_005422.4(TECTA):c.5510G>A (p.Cys1837Tyr)	TBCEL-TECTA	Likely pathogenic	criteria provided, single submitter
3780701	NM_005422.4(TECTA):c.156del (p.Ile53fs)	TBCEL-TECTA	Likely pathogenic	criteria provided, single submitter
3075725	NM_005422.4(TECTA):c.568A>C (p.Thr190Pro)	TECTA	Likely pathogenic	criteria provided, single submitter
3250403	NM_005422.4(TECTA):c.1301G>T (p.Gly434Val)	TECTA	Likely pathogenic	criteria provided, single submitter
4687905	NM_005422.4(TECTA):c.1734dup (p.Gly579fs)	TECTA	Likely pathogenic	criteria provided, single submitter
7024	NM_005422.4(TECTA):c.5331G>A (p.Leu1777=)	TECTA	Likely pathogenic	criteria provided, single submitter
869465	NM_005422.4(TECTA):c.5539T>C (p.Ser1847Pro)	TECTA	Likely pathogenic	criteria provided, single submitter
178636	NM_005422.4(TECTA):c.2781T>C (p.His927=)	LOC126861365	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227994	NM_005422.4(TECTA):c.2418G>A (p.Leu806=)	LOC126861365	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229296	NM_005422.4(TECTA):c.2657A>G (p.Asn886Ser)	LOC126861365	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TECTA	Definitive	Autosomal dominant	nonsyndromic genetic hearing loss	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TECTA	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
TECTA	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TECTA	HGNC:11720	ENSG00000109927	O75443	Alpha-tectorin	gencc,clinvar
TBCEL-TECTA	HGNC:54857	ENSG00000285509		TBCEL-TECTA readthrough	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TECTA	Alpha-tectorin	One of the major non-collagenous components of the tectorial membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TECTA	Other/Unknown	no		EGF, VWF_dom, ZP_dom
TBCEL-TECTA	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
parotid gland	1
secondary oocyte	1
primordial germ cell in gonad	1
stromal cell of endometrium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TECTA	166		marker	oocyte, secondary oocyte, parotid gland
TBCEL-TECTA	100	ubiquitous	yes	primordial germ cell in gonad, stromal cell of endometrium, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TECTA	1,137
TBCEL-TECTA	0

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TECTA	O75443	77.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Post-translational modification: synthesis of GPI-anchored proteins	1	167.9×	0.018	TECTA
Post-translational protein modification	1	19.2×	0.078	TECTA
Metabolism of proteins	1	12.4×	0.081	TECTA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
auditory receptor cell stereocilium organization	1	842.6×	0.004	TECTA
cell-matrix adhesion	1	163.6×	0.009	TECTA
sensory perception of sound	1	100.9×	0.010	TECTA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TECTA	0	0
TBCEL-TECTA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	TECTA, TBCEL-TECTA

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TECTA	0	—
TBCEL-TECTA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.