Hearing loss, autosomal dominant 82

Summary

Hearing loss, autosomal dominant 82 (MONDO:0030719) is a disease caused by ATP2B2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ATP2B2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 82
Mondo ID	MONDO:0030719
OMIM	619804
DOID	DOID:0070603
UMLS	C5676948
MedGen	1803416
GARD	0025622
Is cancer (heuristic)	no

Also known as: deafness, autosomal dominant 82 · DFNA82

Data availability: 19 ClinVar variants · 3 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 › hearing loss, autosomal dominant 82

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 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

19 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 6 uncertain significance, 5 pathogenic, 1 conflicting classifications of pathogenicity, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1525986	NM_001001331.4(ATP2B2):c.955del (p.Ala319fs)	ATP2B2	Pathogenic	no assertion criteria provided
1525987	NM_001001331.4(ATP2B2):c.2329C>T (p.Arg777Ter)	ATP2B2	Pathogenic	no assertion criteria provided
1525988	NM_001001331.4(ATP2B2):c.1963G>T (p.Glu655Ter)	ATP2B2	Pathogenic	no assertion criteria provided
1525989	NM_001001331.4(ATP2B2):c.1998C>A (p.Cys666Ter)	ATP2B2	Pathogenic	no assertion criteria provided
3366952	NM_001001331.4(ATP2B2):c.1043-2A>G	ATP2B2	Pathogenic	criteria provided, single submitter
1705725	NM_001001331.4(ATP2B2):c.945dup (p.Asp316fs)	ATP2B2	Likely pathogenic	criteria provided, single submitter
3250383	NM_001001331.4(ATP2B2):c.3430G>A (p.Val1144Met)	ATP2B2	Likely pathogenic	criteria provided, single submitter
421722	NM_001001331.4(ATP2B2):c.1369G>A (p.Glu457Lys)	ATP2B2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4277335	NM_001001331.4(ATP2B2):c.2194G>A (p.Gly732Ser)	ATP2B2	Likely pathogenic	criteria provided, single submitter
4291897	NM_001001331.4(ATP2B2):c.361del (p.Leu121fs)	ATP2B2	Likely pathogenic	criteria provided, single submitter
4687914	NM_001001331.4(ATP2B2):c.3016C>T (p.Gln1006Ter)	ATP2B2	Likely pathogenic	criteria provided, single submitter
1510104	NM_001001331.4(ATP2B2):c.2953G>A (p.Ala985Thr)	ATP2B2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2431487	NM_001001331.4(ATP2B2):c.919G>A (p.Gly307Arg)	ATP2B2	Uncertain significance	criteria provided, single submitter
2439377	NM_001001331.4(ATP2B2):c.1046A>G (p.Lys349Arg)	ATP2B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2501840	NM_001001331.4(ATP2B2):c.2336A>G (p.Asp779Gly)	ATP2B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393386	NM_001001331.4(ATP2B2):c.1129A>C (p.Ser377Arg)	ATP2B2	Uncertain significance	criteria provided, single submitter
3393410	NM_001001331.4(ATP2B2):c.3059G>A (p.Arg1020His)	ATP2B2	Uncertain significance	criteria provided, single submitter
3900714	NM_001001331.4(ATP2B2):c.3487T>C (p.Ser1163Pro)	ATP2B2	Uncertain significance	criteria provided, single submitter
2572023	NM_001001331.4(ATP2B2):c.727G>A (p.Gly243Arg)	ATP2B2	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
ATP2B2	Definitive	Autosomal dominant	hearing loss, autosomal dominant 82	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP2B2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
ATP2B2	HGNC:815	ENSG00000157087	Q01814	Plasma membrane calcium-transporting ATPase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP2B2	Plasma membrane calcium-transporting ATPase 2	ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP2B2	Transcription factor	no	7.2.2.10	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cation-transptr_C

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
Brodmann (1909) area 46	1
endothelial cell	1
lateral nuclear group of thalamus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP2B2	203	tissue_specific	marker	lateral nuclear group of thalamus, endothelial cell, Brodmann (1909) area 46

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP2B2	3,932

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP2B2	Q01814	73.83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Reduction of cytosolic Ca++ levels	1	951.7×	0.008	ATP2B2
Platelet calcium homeostasis	1	713.8×	0.008	ATP2B2
Platelet homeostasis	1	278.5×	0.010	ATP2B2
Ion transport by P-type ATPases	1	207.6×	0.010	ATP2B2
Ion homeostasis	1	203.9×	0.010	ATP2B2
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.010	ATP2B2
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.011	ATP2B2
Cardiac conduction	1	108.8×	0.014	ATP2B2
Ion channel transport	1	96.0×	0.014	ATP2B2
Muscle contraction	1	77.2×	0.016	ATP2B2
Hemostasis	1	36.0×	0.030	ATP2B2
Transport of small molecules	1	25.1×	0.040	ATP2B2

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
regulation of cardiac conduction	1	842.6×	0.007	ATP2B2
regulation of cytosolic calcium ion concentration	1	383.0×	0.008	ATP2B2
monoatomic ion transmembrane transport	1	208.1×	0.008	ATP2B2
calcium ion transport	1	181.2×	0.008	ATP2B2
sensory perception of sound	1	100.9×	0.010	ATP2B2
neuron differentiation	1	100.3×	0.010	ATP2B2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
ATP2B2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP2B2	7.2.2.10	P-type Ca2+ transporter

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	1	ATP2B2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATP2B2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.