Autosomal recessive nonsyndromic hearing loss 32

Summary

Autosomal recessive nonsyndromic hearing loss 32 (MONDO:0012091) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 32
Mondo ID	MONDO:0012091
MeSH	C563884
OMIM	608653
DOID	DOID:0110466, DOID:0110491
UMLS	C1837608
MedGen	373370
GARD	0022610
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 105 · autosomal recessive deafness 32 · autosomal recessive nonsyndromic deafness 105 · autosomal recessive nonsyndromic deafness 32 · autosomal recessive nonsyndromic deafness caused by mutation in CDC14A · autosomal recessive nonsyndromic deafness type 105 · autosomal recessive nonsyndromic deafness type 32 · CDC14A autosomal recessive nonsyndromic deafness · deafness, autosomal recessive 105 · deafness, autosomal recessive 32 · deafness, autosomal recessive 32, with or without immotile sperm · deafness, autosomal recessive type 105 · DFNB105 · DFNB32

Data availability: 17 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 recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 32

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

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

17 retrieved; paginated sample, class counts are floors:

4 pathogenic/likely pathogenic, 3 benign, 3 likely pathogenic, 3 pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
235145	NM_003672.4(CDC14A):c.1126C>T (p.Arg376Ter)	CDC14A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
235146	NM_003672.4(CDC14A):c.1015C>T (p.Arg339Ter)	CDC14A	Pathogenic	criteria provided, multiple submitters, no conflicts
559435	NM_003672.4(CDC14A):c.935G>A (p.Arg312Gln)	CDC14A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
559436	NM_003672.4(CDC14A):c.934C>G (p.Arg312Gly)	CDC14A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
559437	NM_003672.4(CDC14A):c.376del (p.Tyr126fs)	CDC14A	Pathogenic	no assertion criteria provided
559439	NM_003672.4(CDC14A):c.1033C>T (p.Arg345Ter)	CDC14A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
638290	NM_003672.4(CDC14A):c.417C>G (p.Tyr139Ter)	CDC14A	Pathogenic	criteria provided, single submitter
1299312	NM_003672.4(CDC14A):c.50-1G>T	CDC14A	Likely pathogenic	criteria provided, single submitter
559438	NM_003672.4(CDC14A):c.839-3C>G	CDC14A	Likely pathogenic	criteria provided, single submitter
638289	NM_003672.4(CDC14A):c.959A>C (p.Gln320Pro)	CDC14A	Likely pathogenic	criteria provided, single submitter
1028516	NM_003672.4(CDC14A):c.1251-5C>T	CDC14A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028517	NM_003672.4(CDC14A):c.1745G>A (p.Arg582His)	CDC14A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4526587	NM_003672.4(CDC14A):c.643T>G (p.Tyr215Asp)	CDC14A	Uncertain significance	criteria provided, single submitter
1181745	NM_003672.4(CDC14A):c.1251-139A>G	CDC14A	Benign	criteria provided, multiple submitters, no conflicts
1192711	NM_003672.4(CDC14A):c.-47T>C	CDC14A	Benign	criteria provided, multiple submitters, no conflicts
1192712	NM_003672.4(CDC14A):c.839-124T>C	CDC14A	Benign	criteria provided, multiple submitters, no conflicts
667084	NM_003672.4(CDC14A):c.457-6T>C	CDC14A	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CDC14A	Definitive	Autosomal recessive	nonsyndromic genetic hearing loss	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDC14A	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
CDC14A	HGNC:1718	ENSG00000079335	Q9UNH5	Dual specificity protein phosphatase CDC14A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDC14A	Dual specificity protein phosphatase CDC14A	Dual-specificity phosphatase.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDC14A	Phosphatase	yes		Tyr_Pase_dom, Tyr_Pase_cat, Tyr_Pase_AS

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
buccal mucosa cell	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDC14A	222	ubiquitous	marker	sperm, male germ cell, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDC14A	2,148

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDC14A	Q9UNH5	73.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	1	519.1×	0.008	CDC14A
APC/C-mediated degradation of cell cycle proteins	1	335.9×	0.008	CDC14A
Regulation of mitotic cell cycle	1	335.9×	0.008	CDC14A
MAPK6/MAPK4 signaling	1	135.9×	0.015	CDC14A
MAPK family signaling cascades	1	102.9×	0.016	CDC14A
Cell Cycle, Mitotic	1	48.2×	0.028	CDC14A
Cell Cycle	1	36.0×	0.032	CDC14A
Signal Transduction	1	10.2×	0.098	CDC14A

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 exit from mitosis	1	1203.7×	0.005	CDC14A
positive regulation of cytokinesis	1	401.2×	0.007	CDC14A
microtubule cytoskeleton organization	1	121.2×	0.015	CDC14A
sensory perception of sound	1	100.9×	0.015	CDC14A
cilium assembly	1	73.6×	0.016	CDC14A
cell division	1	46.2×	0.022	CDC14A

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
CDC14A	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
CDC14A	19	Binding:18, ADMET: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	0
D	Druggable family + AlphaFold only, no drug	1	CDC14A
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)
CDC14A	19	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.