Hearing loss, autosomal dominant 72

Summary

Hearing loss, autosomal dominant 72 (MONDO:0033259) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 72
Mondo ID	MONDO:0033259
OMIM	617606
DOID	DOID:0080268
UMLS	C4539886
MedGen	1614203
GARD	0018148
Is cancer (heuristic)	no

Also known as: autosomal dominant nonsyndromic deafness 72 · deafness, autosomal dominant 72 · DFNA72

Data availability: 12 ClinVar variants · 1 GenCC gene-disease record.

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 › hearing loss, autosomal dominant 72

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 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 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

12 retrieved; paginated sample, class counts are floors:

7 benign, 3 uncertain significance, 1 conflicting classifications of pathogenicity, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
1879650	NM_025257.3(SLC44A4):c.40_40+7del	EHMT2-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028383	NM_025257.3(SLC44A4):c.997C>T (p.Arg333Trp)	SLC44A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2909268	NM_025257.3(SLC44A4):c.71G>A (p.Arg24Gln)	SLC44A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
4277934	NM_025257.3(SLC44A4):c.1117G>A (p.Ala373Thr)	SLC44A4	Uncertain significance	criteria provided, single submitter
431429	NM_025257.3(SLC44A4):c.466A>G (p.Met156Val)	SLC44A4	no classifications from unflagged records	no classifications from unflagged records
1224894	NM_025257.3(SLC44A4):c.559G>A (p.Val187Ile)	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts
1230720	NM_025257.3(SLC44A4):c.976A>G (p.Met326Val)	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts
1237774	NM_025257.3(SLC44A4):c.1130+45G>T	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts
1242534	NM_025257.3(SLC44A4):c.937+44C>T	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts
1258488	NM_025257.3(SLC44A4):c.938-11G>A	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts
1279733	NM_025257.3(SLC44A4):c.813C>T (p.Tyr271=)	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts
1290115	NM_025257.3(SLC44A4):c.537G>A (p.Gly179=)	SLC44A4	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SLC44A4	Supportive	Autosomal dominant	autosomal dominant nonsyndromic hearing loss	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC44A4	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
SLC44A4	HGNC:13941	ENSG00000204385	Q53GD3	Choline transporter-like protein 4	gencc,clinvar
EHMT2-AS1	HGNC:39751	ENSG00000237080		EHMT2 and SLC44A4 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC44A4	Choline transporter-like protein 4	Choline transporter that plays a role in the choline-acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the prote…

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)
SLC44A4	Other/Unknown	no		Choline_transptr-like
EHMT2-AS1	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
mucosa of transverse colon	2
rectum	1
right uterine tube	1
pancreatic ductal cell	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC44A4	130	tissue_specific	marker	mucosa of transverse colon, right uterine tube, rectum
EHMT2-AS1	153		yes	mucosa of transverse colon, pancreatic ductal cell, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC44A4	892
EHMT2-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC44A4	Q53GD3	83.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
SLC-mediated bile acid transport	1	1631.4×	0.001	SLC44A4
Synthesis of PC	1	407.9×	0.002	SLC44A4

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
neuromast hair cell development	1	16852.0×	3e-04	SLC44A4
acetylcholine secretion	1	16852.0×	3e-04	SLC44A4
thiamine pyrophosphate transmembrane transport	1	8426.0×	3e-04	SLC44A4
otolith formation	1	8426.0×	3e-04	SLC44A4
acetylcholine biosynthetic process	1	5617.3×	3e-04	SLC44A4
choline transport	1	1532.0×	1e-03	SLC44A4
phosphatidylcholine biosynthetic process	1	802.5×	0.002	SLC44A4
positive regulation of cell growth	1	183.2×	0.006	SLC44A4
transmembrane transport	1	168.5×	0.006	SLC44A4

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
SLC44A4	0	0
EHMT2-AS1	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	SLC44A4, EHMT2-AS1

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)
SLC44A4	0	—
EHMT2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.