Hearing loss, autosomal dominant 78

Summary

Hearing loss, autosomal dominant 78 (MONDO:0033665) is a disease caused by SLC12A2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC12A2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 78
Mondo ID	MONDO:0033665
OMIM	619081
DOID	DOID:0112159
UMLS	C5436768
MedGen	1777362
GARD	0018156
Is cancer (heuristic)	no

Also known as: deafness, autosomal dominant 78 · DFNA78

Data availability: 46 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 78

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 72, hearing loss, autosomal dominant 73, hearing loss, autosomal dominant 34, with or without inflammation, 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

46 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 10 benign/likely benign, 8 likely benign, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 pathogenic; association, 2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
804307	NM_001046.3(SLC12A2):c.2941G>T (p.Asp981Tyr)	SLC12A2	Pathogenic; association	no assertion criteria provided
804308	NM_001046.3(SLC12A2):c.2930-2A>G	SLC12A2	Pathogenic; association	no assertion criteria provided
804310	NM_001046.3(SLC12A2):c.2935G>A (p.Glu979Lys)	SLC12A2	Pathogenic	criteria provided, single submitter
984668	NM_001046.3(SLC12A2):c.2938G>A (p.Glu980Lys)	SLC12A2	Pathogenic	no assertion criteria provided
3601713	NM_001046.3(SLC12A2):c.2959C>T (p.Gln987Ter)	SLC12A2	Likely pathogenic	criteria provided, single submitter
3601714	NM_001046.3(SLC12A2):c.2977+1G>A	SLC12A2	Likely pathogenic	criteria provided, single submitter
3780607	NM_001046.3(SLC12A2):c.3147G>A (p.Trp1049Ter)	SLC12A2	Likely pathogenic	criteria provided, single submitter
1385353	NM_001046.3(SLC12A2):c.288GGC[10] (p.Ala105_Ala107dup)	LOC129994526	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1335592	NM_001046.3(SLC12A2):c.953-7C>T	SLC12A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1671022	NM_001046.3(SLC12A2):c.562GGC[6] (p.Gly192dup)	SLC12A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1365125	NM_001046.3(SLC12A2):c.41G>T (p.Gly14Val)	LOC129994526	Uncertain significance	criteria provided, multiple submitters, no conflicts
1440806	NM_001046.3(SLC12A2):c.288GGC[11] (p.Ala104_Ala107dup)	LOC129994526	Uncertain significance	criteria provided, multiple submitters, no conflicts
1510335	NM_001046.3(SLC12A2):c.235A>C (p.Ser79Arg)	LOC129994526	Uncertain significance	criteria provided, multiple submitters, no conflicts
1373721	NM_001046.3(SLC12A2):c.3622C>G (p.Leu1208Val)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1385672	NM_001046.3(SLC12A2):c.788A>C (p.Glu263Ala)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1401954	NM_001046.3(SLC12A2):c.2293C>G (p.Leu765Val)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1445687	NM_001046.3(SLC12A2):c.2848G>A (p.Val950Met)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1473763	NM_001046.3(SLC12A2):c.2210T>A (p.Leu737Gln)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1476334	NM_001046.3(SLC12A2):c.1127A>G (p.Asn376Ser)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1497323	NM_001046.3(SLC12A2):c.2639A>G (p.Lys880Arg)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1505967	NM_001046.3(SLC12A2):c.881G>A (p.Arg294His)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2156078	NM_001046.3(SLC12A2):c.376A>T (p.Ser126Cys)	SLC12A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064020	NM_001046.3(SLC12A2):c.2930-5T>A	SLC12A2	Uncertain significance	criteria provided, single submitter
3376954	NM_001046.3(SLC12A2):c.3364A>G (p.Ile1122Val)	SLC12A2	Uncertain significance	criteria provided, single submitter
3892444	NM_001046.3(SLC12A2):c.2888A>G (p.Asp963Gly)	SLC12A2	Uncertain significance	criteria provided, single submitter
3892445	NM_001046.3(SLC12A2):c.3131C>T (p.Thr1044Met)	SLC12A2	Uncertain significance	criteria provided, single submitter
804309	NM_001046.3(SLC12A2):c.2962C>A (p.Pro988Thr)	SLC12A2	Uncertain significance	criteria provided, single submitter
1532036	NM_001046.3(SLC12A2):c.261C>T (p.Ser87=)	LOC129994526	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1355224	NM_001046.3(SLC12A2):c.2511C>T (p.Ile837=)	SLC12A2	Likely benign	criteria provided, multiple submitters, no conflicts
1424361	NM_001046.3(SLC12A2):c.1941A>G (p.Lys647=)	SLC12A2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
SLC12A2	Strong	Autosomal dominant	hearing loss, autosomal dominant 78	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
inferior vagus X ganglion	1
palpebral conjunctiva	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC12A2	2,461

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC12A2	P55011	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 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
Cation-coupled Chloride cotransporters	1	1631.4×	0.002	SLC12A2
R-HSA-425393	1	129.8×	0.015	SLC12A2
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC12A2
Transport of small molecules	1	25.1×	0.040	SLC12A2

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
positive regulation of cell volume	1	16852.0×	7e-04	SLC12A2
inorganic anion import across plasma membrane	1	8426.0×	7e-04	SLC12A2
inorganic cation import across plasma membrane	1	8426.0×	7e-04	SLC12A2
positive regulation of aspartate secretion	1	8426.0×	7e-04	SLC12A2
regulation of matrix metallopeptidase secretion	1	8426.0×	7e-04	SLC12A2
regulation of spontaneous synaptic transmission	1	4213.0×	0.001	SLC12A2
negative regulation of vascular wound healing	1	3370.4×	0.001	SLC12A2
transepithelial ammonium transport	1	3370.4×	0.001	SLC12A2
transepithelial chloride transport	1	1872.4×	0.001	SLC12A2
ammonium transmembrane transport	1	1872.4×	0.001	SLC12A2
hyperosmotic response	1	1685.2×	0.001	SLC12A2
intracellular chloride ion homeostasis	1	1685.2×	0.001	SLC12A2
chloride ion homeostasis	1	1532.0×	0.001	SLC12A2
T cell chemotaxis	1	1123.5×	0.002	SLC12A2
cellular response to potassium ion	1	1053.2×	0.002	SLC12A2
intracellular potassium ion homeostasis	1	991.3×	0.002	SLC12A2
cellular response to chemokine	1	991.3×	0.002	SLC12A2
sodium ion homeostasis	1	936.2×	0.002	SLC12A2
intracellular sodium ion homeostasis	1	766.0×	0.002	SLC12A2
potassium ion homeostasis	1	766.0×	0.002	SLC12A2
sodium ion import across plasma membrane	1	624.1×	0.002	SLC12A2
cell volume homeostasis	1	601.9×	0.002	SLC12A2
gamma-aminobutyric acid signaling pathway	1	543.6×	0.002	SLC12A2
maintenance of blood-brain barrier	1	481.5×	0.003	SLC12A2
potassium ion import across plasma membrane	1	366.4×	0.003	SLC12A2
chloride transmembrane transport	1	237.3×	0.005	SLC12A2
sodium ion transmembrane transport	1	203.0×	0.005	SLC12A2
transport across blood-brain barrier	1	179.3×	0.006	SLC12A2
monoatomic ion transport	1	156.0×	0.006	SLC12A2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC12A2	BUMETANIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC12A2	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BUMETANIDE	4	SLC12A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC12A2	13	Binding:9, Functional:4

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
BUMETANIDE	4	SLC12A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC12A2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.