Hearing loss, autosomal dominant 75

Summary

Hearing loss, autosomal dominant 75 (MONDO:0032911) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 75
Mondo ID	MONDO:0032911
OMIM	618778
DOID	DOID:0112166
UMLS	C5394059
MedGen	1713569
GARD	0018153
Is cancer (heuristic)	no

Also known as: DEAFNESS, AUTOSOMAL DOMINANT 75 · deafness, autosomal dominant 75 · DFNA75

Data availability: 23 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 › hearing loss, autosomal dominant 75

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 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

23 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 2 benign, 2 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
975628	NM_001375524.1(TRRAP):c.9952A>G (p.Met3318Val)	TRRAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024225	NM_001375524.1(TRRAP):c.2622+1G>A	TRRAP	Likely pathogenic	criteria provided, single submitter
2791953	NM_001375524.1(TRRAP):c.10307C>T (p.Thr3436Met)	TRRAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3777020	NM_001375524.1(TRRAP):c.5084C>T (p.Thr1695Ile)	LOC126860121	Uncertain significance	criteria provided, single submitter
1679670	NM_001375524.1(TRRAP):c.9500G>A (p.Arg3167Gln)	TRRAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441838	NM_001375524.1(TRRAP):c.5974A>C (p.Met1992Leu)	TRRAP	Uncertain significance	criteria provided, single submitter
2442046	NM_001375524.1(TRRAP):c.8750T>C (p.Met2917Thr)	TRRAP	Uncertain significance	criteria provided, single submitter
2442113	NM_001375524.1(TRRAP):c.4804A>G (p.Lys1602Glu)	TRRAP	Uncertain significance	criteria provided, single submitter
2575894	NM_001375524.1(TRRAP):c.2573_2577del (p.Pro858fs)	TRRAP	Uncertain significance	criteria provided, single submitter
2582431	NM_001375524.1(TRRAP):c.11291C>T (p.Ala3764Val)	TRRAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3248559	NM_001375524.1(TRRAP):c.711+5G>A	TRRAP	Uncertain significance	criteria provided, single submitter
3393409	NM_001375524.1(TRRAP):c.5791A>G (p.Met1931Val)	TRRAP	Uncertain significance	criteria provided, single submitter
3594975	NM_001375524.1(TRRAP):c.2237T>G (p.Leu746Arg)	TRRAP	Uncertain significance	criteria provided, single submitter
3594976	NM_001375524.1(TRRAP):c.2857G>A (p.Ala953Thr)	TRRAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892737	NM_001375524.1(TRRAP):c.278T>C (p.Val93Ala)	TRRAP	Uncertain significance	criteria provided, single submitter
3892738	NM_001375524.1(TRRAP):c.4543G>A (p.Val1515Ile)	TRRAP	Uncertain significance	criteria provided, single submitter
3892739	NM_001375524.1(TRRAP):c.7301A>G (p.Asp2434Gly)	TRRAP	Uncertain significance	criteria provided, single submitter
4072260	NM_001375524.1(TRRAP):c.1715-45A>G	TRRAP	Uncertain significance	criteria provided, single submitter
973887	NM_001375524.1(TRRAP):c.8738G>A (p.Arg2913His)	TRRAP	Uncertain significance	criteria provided, single submitter
1269922	NM_001375524.1(TRRAP):c.2200-46C>T	TRRAP	Benign	criteria provided, multiple submitters, no conflicts
1283529	NM_001375524.1(TRRAP):c.898-46C>T	TRRAP	Benign	criteria provided, multiple submitters, no conflicts
2073658	NM_001375524.1(TRRAP):c.8271G>C (p.Glu2757Asp)	TRRAP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
812648	NM_001375524.1(TRRAP):c.511C>T (p.Arg171Cys)	TRRAP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
TRRAP	Supportive	Autosomal dominant	autosomal dominant nonsyndromic hearing loss	8

Orphanet rare-disease linkage (cohort genes)

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

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
TRRAP	HGNC:12347	ENSG00000196367	Q9Y4A5	Transformation/transcription domain-associated protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRRAP	Transformation/transcription domain-associated protein	Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRRAP	Kinase	yes		PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_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
ganglionic eminence	1
sural nerve	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRRAP	241	ubiquitous	marker	ventricular zone, sural nerve, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRRAP	4,847

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRRAP	Q9Y4A5	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.019	TRRAP
HATs acetylate histones	1	79.3×	0.019	TRRAP
Ub-specific processing proteases	1	53.1×	0.019	TRRAP

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
DNA repair-dependent chromatin remodeling	1	674.1×	0.009	TRRAP
regulation of double-strand break repair	1	581.1×	0.009	TRRAP
positive regulation of double-strand break repair via homologous recombination	1	383.0×	0.009	TRRAP
regulation of DNA repair	1	276.3×	0.009	TRRAP
regulation of RNA splicing	1	218.9×	0.009	TRRAP
regulation of apoptotic process	1	83.4×	0.019	TRRAP
regulation of cell cycle	1	74.6×	0.019	TRRAP
regulation of DNA-templated transcription	1	31.6×	0.040	TRRAP
positive regulation of DNA-templated transcription	1	27.9×	0.040	TRRAP
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TRRAP

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRRAP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TRRAP	1	Binding:1

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	TRRAP
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
TRRAP	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.