Autosomal dominant nonsyndromic hearing loss 56

Summary

Autosomal dominant nonsyndromic hearing loss 56 (MONDO:0014283) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 89

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 56
Mondo ID	MONDO:0014283
OMIM	615629
DOID	DOID:0110581
UMLS	C3810170
MedGen	816500
GARD	0018137
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 56 · autosomal dominant nonsyndromic deafness 56 · autosomal dominant nonsyndromic deafness caused by mutation in TNC · autosomal dominant nonsyndromic deafness type 56 · deafness, autosomal dominant 56 · deafness, autosomal dominant type 56 · DFNA56 · TNC autosomal dominant nonsyndromic deafness

Data availability: 89 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 56

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 12, 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 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

89 retrieved; paginated sample, class counts are floors:

34 benign, 29 uncertain significance, 15 benign/likely benign, 7 conflicting classifications of pathogenicity, 2 pathogenic, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2775398	NM_002160.4(TNC):c.5247A>T (p.Gly1749=)	TNC	Pathogenic	no assertion criteria provided
97009	NM_002160.4(TNC):c.5386A>T (p.Thr1796Ser)	TNC	Pathogenic	no assertion criteria provided
3250407	NM_002160.4(TNC):c.323G>A (p.Arg108His)	TNC	Likely pathogenic	criteria provided, single submitter
2355277	NM_002160.4(TNC):c.5128A>G (p.Met1710Val)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2673188	NM_002160.4(TNC):c.5978C>T (p.Thr1993Met)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3180122	NM_002160.4(TNC):c.2941G>A (p.Ala981Thr)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3459054	NM_002160.4(TNC):c.625G>A (p.Asp209Asn)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
689600	NM_002160.4(TNC):c.2340G>T (p.Glu780Asp)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
805674	NM_002160.4(TNC):c.2374G>T (p.Gly792Cys)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
97008	NM_002160.4(TNC):c.5317G>A (p.Val1773Met)	TNC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
560147	Single allele	DELEC1	Uncertain significance	criteria provided, single submitter
1029564	NM_002160.4(TNC):c.1580G>C (p.Cys527Ser)	TNC	Uncertain significance	criteria provided, single submitter
1029565	NM_002160.4(TNC):c.2239C>T (p.Arg747Trp)	TNC	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033486	NM_002160.4(TNC):c.2795G>C (p.Gly932Ala)	TNC	Uncertain significance	criteria provided, single submitter
1806244	NM_002160.4(TNC):c.2434A>G (p.Lys812Glu)	TNC	Uncertain significance	criteria provided, single submitter
2437125	NM_002160.4(TNC):c.1622G>A (p.Arg541His)	TNC	Uncertain significance	criteria provided, single submitter
2437126	NM_002160.4(TNC):c.6527A>G (p.Glu2176Gly)	TNC	Uncertain significance	criteria provided, single submitter
2437127	NM_002160.4(TNC):c.1004G>C (p.Gly335Ala)	TNC	Uncertain significance	criteria provided, single submitter
2437128	NM_002160.4(TNC):c.5692G>A (p.Val1898Ile)	TNC	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441982	NM_002160.4(TNC):c.4490G>C (p.Gly1497Ala)	TNC	Uncertain significance	criteria provided, single submitter
2664067	NM_002160.4(TNC):c.2192A>C (p.Glu731Ala)	TNC	Uncertain significance	no assertion criteria provided
3234848	NM_002160.4(TNC):c.1973C>A (p.Pro658His)	TNC	Uncertain significance	criteria provided, single submitter
3237485	NM_002160.4(TNC):c.4079G>A (p.Trp1360Ter)	TNC	Uncertain significance	criteria provided, single submitter
3366995	NM_002160.4(TNC):c.3442A>G (p.Ile1148Val)	TNC	Uncertain significance	criteria provided, multiple submitters, no conflicts
3367120	NM_002160.4(TNC):c.848T>C (p.Leu283Pro)	TNC	Uncertain significance	criteria provided, single submitter
3391819	NM_002160.4(TNC):c.3295_3297delinsAAT (p.Gln1099Asn)	TNC	Uncertain significance	criteria provided, single submitter
3393391	NM_002160.4(TNC):c.3047G>A (p.Arg1016His)	TNC	Uncertain significance	criteria provided, single submitter
3393408	NM_002160.4(TNC):c.2447A>G (p.Asp816Gly)	TNC	Uncertain significance	criteria provided, single submitter
3892672	NM_002160.4(TNC):c.2911G>A (p.Asp971Asn)	TNC	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892673	NM_002160.4(TNC):c.4433T>C (p.Leu1478Ser)	TNC	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
TNC	Moderate	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 56	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNC	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNC	HGNC:5318	ENSG00000041982	P24821	Tenascin	gencc,clinvar
DELEC1	HGNC:23658	ENSG00000173077	Q9P2X7	Deleted in esophageal cancer 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNC	Tenascin	Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration.
DELEC1	Deleted in esophageal cancer 1	Candidate tumor suppressor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNC	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
DELEC1	Other/Unknown	no		DEC1

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
popliteal artery	1
saphenous vein	1
tibial artery	1
granulocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNC	272	ubiquitous	marker	saphenous vein, tibial artery, popliteal artery
DELEC1	154	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNC	1,355
DELEC1	37

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNC	P24821	21

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DELEC1	Q9P2X7	62.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Syndecan interactions	1	423.0×	0.017	TNC
Non-integrin membrane-ECM interactions	1	154.3×	0.017	TNC
ECM proteoglycans	1	150.3×	0.017	TNC
Integrin cell surface interactions	1	134.3×	0.017	TNC
Post-translational protein phosphorylation	1	100.2×	0.017	TNC
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.017	TNC
Extracellular matrix organization	1	63.1×	0.020	TNC
Post-translational protein modification	1	19.2×	0.059	TNC
Metabolism of proteins	1	12.4×	0.081	TNC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mesenchymal-epithelial cell signaling involved in prostate gland development	1	4213.0×	0.004	TNC
bud outgrowth involved in lung branching	1	2808.7×	0.004	TNC
cellular response to prostaglandin D stimulus	1	1203.7×	0.004	TNC
peripheral nervous system axon regeneration	1	1053.2×	0.004	TNC
response to fibroblast growth factor	1	1053.2×	0.004	TNC
prostate gland epithelium morphogenesis	1	936.2×	0.004	TNC
cellular response to vitamin D	1	766.0×	0.004	TNC
neuromuscular junction development	1	263.3×	0.011	TNC
negative regulation of cell adhesion	1	191.5×	0.012	TNC
morphogenesis of an epithelium	1	172.0×	0.012	TNC
regulation of cell adhesion	1	153.2×	0.012	TNC
response to mechanical stimulus	1	150.5×	0.012	TNC
odontogenesis of dentin-containing tooth	1	150.5×	0.012	TNC
cellular response to retinoic acid	1	117.0×	0.013	TNC
regulation of cell growth	1	110.9×	0.013	TNC
response to wounding	1	110.9×	0.013	TNC
regulation of inflammatory response	1	84.3×	0.017	TNC
regulation of cell migration	1	78.8×	0.017	TNC
response to ethanol	1	73.3×	0.017	TNC
osteoblast differentiation	1	60.6×	0.020	TNC
negative regulation of cell population proliferation	1	21.1×	0.054	DELEC1
positive regulation of gene expression	1	19.4×	0.055	TNC
cell adhesion	1	18.7×	0.055	TNC
positive regulation of cell population proliferation	1	16.8×	0.059	TNC

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNC	0	0
DELEC1	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	1	TNC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DELEC1

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)
TNC	0	—
DELEC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.