Autosomal dominant nonsyndromic hearing loss 7

Summary

Autosomal dominant nonsyndromic hearing loss 7 (MONDO:0011074) is a disease caused by LMX1A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LMX1A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 7
Mondo ID	MONDO:0011074
MeSH	C563321
OMIM	601412
DOID	DOID:0110591
UMLS	C1832379
MedGen	318614
GARD	0018106
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 7 · autosomal dominant nonsyndromic deafness 7 · autosomal dominant nonsyndromic deafness type 7 · deafness, autosomal dominant 7 · DFNA7

Data availability: 19 ClinVar variants · 4 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 7

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 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 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:

9 uncertain significance, 4 likely pathogenic, 4 pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1705342	NM_177398.4(LMX1A):c.595A>G (p.Arg199Gly)	LMX1A	Pathogenic	criteria provided, single submitter
1723178	NM_177398.4(LMX1A):c.622C>T (p.Arg208Ter)	LMX1A	Pathogenic	criteria provided, single submitter
812515	NM_177398.4(LMX1A):c.721G>C (p.Val241Leu)	LMX1A	Pathogenic	no assertion criteria provided
812516	NM_177398.4(LMX1A):c.290G>C (p.Cys97Ser)	LMX1A	Pathogenic	no assertion criteria provided
1687337	NM_177398.4(LMX1A):c.331del (p.Gln111fs)	LMX1A	Likely pathogenic	criteria provided, single submitter
2503455	NM_177398.4(LMX1A):c.937C>T (p.Arg313Ter)	LMX1A	Likely pathogenic	criteria provided, single submitter
3601196	NM_177398.4(LMX1A):c.596G>A (p.Arg199Lys)	LMX1A	Likely pathogenic	criteria provided, single submitter
4813826	NM_177398.4(LMX1A):c.390_391delinsAT (p.Lys131Ter)	LMX1A	Likely pathogenic	criteria provided, single submitter
1805025	NM_177398.4(LMX1A):c.581G>T (p.Arg194Leu)	LMX1A	Uncertain significance	criteria provided, single submitter
2433492	NM_177398.4(LMX1A):c.874G>A (p.Ala292Thr)	LMX1A	Uncertain significance	criteria provided, single submitter
2664708	NM_177398.4(LMX1A):c.317T>G (p.Phe106Cys)	LMX1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3355759	NM_177398.4(LMX1A):c.581G>A (p.Arg194His)	LMX1A	Uncertain significance	criteria provided, single submitter
3377593	NM_177398.4(LMX1A):c.915T>G (p.Ser305Arg)	LMX1A	Uncertain significance	criteria provided, single submitter
3602621	NM_177398.4(LMX1A):c.683T>A (p.Leu228Gln)	LMX1A	Uncertain significance	criteria provided, single submitter
3891582	NM_177398.4(LMX1A):c.45C>G (p.Ile15Met)	LMX1A	Uncertain significance	criteria provided, single submitter
4685531	NM_177398.4(LMX1A):c.550G>A (p.Gly184Arg)	LMX1A	Uncertain significance	criteria provided, single submitter
4845259	NM_177398.4(LMX1A):c.589C>T (p.Arg197Cys)	LMX1A	Uncertain significance	no assertion criteria provided
1252147	NM_177398.4(LMX1A):c.349C>T (p.Leu117=)	LMX1A	Benign	criteria provided, multiple submitters, no conflicts
1294826	NM_177398.4(LMX1A):c.1050T>C (p.Asp350=)	LMX1A	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 0 · 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
LMX1A	Definitive	Autosomal dominant	autosomal dominant nonsyndromic hearing loss	7

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
LMX1A	HGNC:6653	ENSG00000162761	Q8TE12	LIM homeobox transcription factor 1-alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMX1A	LIM homeobox transcription factor 1-alpha	Acts as a transcriptional activator by binding to an A/T-rich sequence, the FLAT element, in the insulin gene promoter.

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)
LMX1A	Transcription factor	no		HD, Znf_LIM, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

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
apex of heart	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMX1A	92	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, sperm, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMX1A	1,202

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMX1A	Q8TE12	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
olfactory behavior	1	1872.4×	0.006	LMX1A
midbrain dopaminergic neuron differentiation	1	1203.7×	0.006	LMX1A
dentate gyrus development	1	624.1×	0.006	LMX1A
dopaminergic neuron differentiation	1	624.1×	0.006	LMX1A
cerebellum development	1	358.6×	0.007	LMX1A
synapse organization	1	280.9×	0.007	LMX1A
negative regulation of neuron differentiation	1	271.8×	0.007	LMX1A
regulation of cell growth	1	221.7×	0.008	LMX1A
memory	1	183.2×	0.008	LMX1A
locomotory behavior	1	179.3×	0.008	LMX1A
neuron differentiation	1	100.3×	0.013	LMX1A
axon guidance	1	90.6×	0.013	LMX1A
positive regulation of transcription by RNA polymerase II	1	14.9×	0.072	LMX1A
regulation of transcription by RNA polymerase II	1	11.7×	0.086	LMX1A

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
LMX1A	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	1	LMX1A

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)
LMX1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.