Hearing loss, autosomal dominant 83

Summary

Hearing loss, autosomal dominant 83 (MONDO:0030723) is a disease caused by MAP1B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MAP1B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 83
Mondo ID	MONDO:0030723
OMIM	619808
DOID	DOID:0070609
UMLS	C5676951
MedGen	1812664
GARD	0025623
Is cancer (heuristic)	no

Also known as: deafness, autosomal dominant 83 · DFNA83

Data availability: 21 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 83

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 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

21 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1527914	NM_005909.5(MAP1B):c.4198A>G (p.Ser1400Gly)	MAP1B	Pathogenic	no assertion criteria provided
1708214	NM_005909.5(MAP1B):c.2995C>T (p.Arg999Ter)	MAP1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024282	NM_005909.5(MAP1B):c.881del (p.Phe294fs)	MAP1B	Pathogenic	criteria provided, single submitter
2536708	NM_005909.5(MAP1B):c.3001G>A (p.Glu1001Lys)	MAP1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2284909	NM_005909.5(MAP1B):c.4646T>G (p.Val1549Gly)	MAP1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441938	NM_005909.5(MAP1B):c.996G>C (p.Glu332Asp)	MAP1B	Uncertain significance	criteria provided, single submitter
2442022	NM_005909.5(MAP1B):c.5563G>C (p.Gly1855Arg)	MAP1B	Uncertain significance	criteria provided, single submitter
2533063	NM_005909.5(MAP1B):c.6758A>G (p.Lys2253Arg)	MAP1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2671742	NM_005909.5(MAP1B):c.1808C>A (p.Thr603Asn)	MAP1B	Uncertain significance	criteria provided, single submitter
3067960	NM_005909.5(MAP1B):c.7336A>G (p.Met2446Val)	MAP1B	Uncertain significance	criteria provided, single submitter
3356857	NM_005909.5(MAP1B):c.818C>T (p.Ala273Val)	MAP1B	Uncertain significance	criteria provided, single submitter
3362771	NM_005909.5(MAP1B):c.803G>A (p.Gly268Glu)	MAP1B	Uncertain significance	criteria provided, single submitter
3377583	NM_005909.5(MAP1B):c.5842C>T (p.Arg1948Trp)	MAP1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3592755	NM_005909.5(MAP1B):c.5407T>G (p.Ser1803Ala)	MAP1B	Uncertain significance	criteria provided, single submitter
3603279	NM_005909.5(MAP1B):c.5444A>G (p.His1815Arg)	MAP1B	Uncertain significance	criteria provided, single submitter
3891618	NM_005909.5(MAP1B):c.1697C>T (p.Pro566Leu)	MAP1B	Uncertain significance	criteria provided, single submitter
3891619	NM_005909.5(MAP1B):c.4171A>G (p.Ile1391Val)	MAP1B	Uncertain significance	criteria provided, single submitter
3891620	NM_005909.5(MAP1B):c.5689C>T (p.Arg1897Trp)	MAP1B	Uncertain significance	criteria provided, single submitter
3891621	NM_005909.5(MAP1B):c.961A>G (p.Asn321Asp)	MAP1B	Uncertain significance	criteria provided, single submitter
710322	NM_005909.5(MAP1B):c.4902C>T (p.Pro1634=)	MAP1B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
782815	NM_005909.5(MAP1B):c.5193C>A (p.Ser1731=)	MAP1B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
MAP1B	Strong	Autosomal dominant	hearing loss, autosomal dominant 83	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAP1B	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MAP1B	Orphanet:98892	Periventricular nodular heterotopia

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
MAP1B	HGNC:6836	ENSG00000131711	P46821	Microtubule-associated protein 1B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAP1B	Microtubule-associated protein 1B	Facilitates tyrosination of alpha-tubulin in neuronal microtubules.

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)
MAP1B	Other/Unknown	no		MAP1B_neuraxin, MAP1, MAP1B/S_N

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
lateral nuclear group of thalamus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAP1B	299	ubiquitous	marker	lateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAP1B	3,724

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAP1B	P46821	46.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Respiratory Syncytial Virus Infection Pathway	1	196.9×	0.016	MAP1B
RSV-host interactions	1	156.4×	0.016	MAP1B
Viral Infection Pathways	1	30.8×	0.050	MAP1B
Infectious disease	1	24.8×	0.050	MAP1B
Disease	1	13.1×	0.076	MAP1B

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
developmental maturation	1	16852.0×	9e-04	MAP1B
induction of synaptic plasticity by chemical substance	1	16852.0×	9e-04	MAP1B
establishment of monopolar cell polarity	1	8426.0×	0.001	MAP1B
negative regulation of intracellular transport	1	5617.3×	0.001	MAP1B
regulation of microtubule depolymerization	1	4213.0×	0.001	MAP1B
response to insecticide	1	2808.7×	0.002	MAP1B
peripheral nervous system axon regeneration	1	2106.5×	0.002	MAP1B
odontoblast differentiation	1	2106.5×	0.002	MAP1B
response to carbohydrate	1	1685.2×	0.002	MAP1B
mitochondrion transport along microtubule	1	1404.3×	0.002	MAP1B
response to vitamin A	1	1053.2×	0.003	MAP1B
cellular response to peptide hormone stimulus	1	842.6×	0.003	MAP1B
positive regulation of microtubule polymerization	1	674.1×	0.003	MAP1B
microtubule bundle formation	1	510.7×	0.003	MAP1B
positive regulation of axon extension	1	510.7×	0.003	MAP1B
negative regulation of microtubule depolymerization	1	495.6×	0.003	MAP1B
axon extension	1	495.6×	0.003	MAP1B
dendrite development	1	391.9×	0.004	MAP1B
regulation of postsynapse assembly	1	343.9×	0.004	MAP1B
cellular response to growth factor stimulus	1	318.0×	0.005	MAP1B
response to mechanical stimulus	1	300.9×	0.005	MAP1B
synapse assembly	1	230.8×	0.006	MAP1B
response to estradiol	1	198.3×	0.006	MAP1B
positive regulation of neuron differentiation	1	198.3×	0.006	MAP1B
axonogenesis	1	160.5×	0.007	MAP1B
neuron migration	1	133.8×	0.008	MAP1B
neuron projection development	1	122.1×	0.009	MAP1B
microtubule cytoskeleton organization	1	121.2×	0.009	MAP1B
response to xenobiotic stimulus	1	69.1×	0.014	MAP1B

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
MAP1B	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
MAP1B	10	Binding:6, 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

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	MAP1B

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)
MAP1B	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.