Autosomal recessive nonsyndromic hearing loss 86

Summary

Autosomal recessive nonsyndromic hearing loss 86 (MONDO:0013826) is a disease caused by TBC1D24 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TBC1D24 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 86
Mondo ID	MONDO:0013826
OMIM	614617
DOID	DOID:0110532
UMLS	C2829265
MedGen	760543
GARD	0022643
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 86 · autosomal recessive nonsyndromic deafness 86 · autosomal recessive nonsyndromic deafness caused by mutation in TBC1D24 · autosomal recessive nonsyndromic deafness type 86 · deafness, autosomal recessive 86 · deafness, autosomal recessive type 86 · DFNB86 · TBC1D24 autosomal recessive nonsyndromic deafness

Data availability: 41 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 recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 86

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 32, 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 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

41 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 9 pathogenic, 6 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
100677	NM_001199107.2(TBC1D24):c.208G>T (p.Asp70Tyr)	TBC1D24	Pathogenic	no assertion criteria provided
100678	NM_001199107.2(TBC1D24):c.878G>C (p.Arg293Pro)	TBC1D24	Pathogenic	no assertion criteria provided
133246	NM_001199107.2(TBC1D24):c.533C>T (p.Ser178Leu)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456664	NM_001199107.2(TBC1D24):c.752del (p.Phe251fs)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
207499	NM_001199107.2(TBC1D24):c.457G>A (p.Glu153Lys)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236046	NM_001199107.2(TBC1D24):c.194G>T (p.Arg65Leu)	TBC1D24	Pathogenic	no assertion criteria provided
3601867	NM_001199107.2(TBC1D24):c.76G>T (p.Glu26Ter)	TBC1D24	Pathogenic	criteria provided, single submitter
421795	NM_001199107.2(TBC1D24):c.1360_1363dup (p.Pro455fs)	TBC1D24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
474302	NM_001199107.2(TBC1D24):c.116C>T (p.Ala39Val)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
523796	NM_001199107.2(TBC1D24):c.619C>T (p.Gln207Ter)	TBC1D24	Pathogenic	criteria provided, multiple submitters, no conflicts
587507	NM_001199107.2(TBC1D24):c.346A>T (p.Lys116Ter)	TBC1D24	Pathogenic	criteria provided, single submitter
977227	NM_001199107.2(TBC1D24):c.965+1G>A	TBC1D24	Pathogenic	no assertion criteria provided
3601864	NM_001199107.2(TBC1D24):c.1207-1G>C	TBC1D24	Likely pathogenic	criteria provided, single submitter
3601865	NM_001199107.2(TBC1D24):c.1505del (p.Gly502fs)	TBC1D24	Likely pathogenic	criteria provided, single submitter
3601866	NM_001199107.2(TBC1D24):c.1526G>C (p.Gly509Ala)	TBC1D24	Likely pathogenic	criteria provided, single submitter
130540	NM_001199107.2(TBC1D24):c.641G>A (p.Arg214His)	CCNF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130541	NM_001199107.2(TBC1D24):c.1015A>G (p.Asn339Asp)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
208413	NM_001199107.2(TBC1D24):c.1327G>A (p.Glu443Lys)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2507172	NM_001199107.2(TBC1D24):c.877C>T (p.Arg293Cys)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
418692	NM_001199107.2(TBC1D24):c.229ATCGTGGGCAAG[1] (p.77IVGK[1])	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
649192	NM_001199107.2(TBC1D24):c.1321C>T (p.Arg441Cys)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1185601	NM_001199107.2(TBC1D24):c.370C>A (p.Gln124Lys)	TBC1D24	Uncertain significance	no assertion criteria provided
1185602	NM_001199107.2(TBC1D24):c.523G>C (p.Ala175Pro)	TBC1D24	Uncertain significance	no assertion criteria provided
1493656	NM_001199107.2(TBC1D24):c.889C>T (p.Arg297Cys)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts
207501	NM_001199107.2(TBC1D24):c.605C>T (p.Ser202Leu)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts
207506	NM_001199107.2(TBC1D24):c.871G>A (p.Ala291Thr)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts
207519	NM_001199107.2(TBC1D24):c.878G>A (p.Arg293His)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts
229287	NM_001199107.2(TBC1D24):c.439G>A (p.Asp147Asn)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382995	NM_001199107.2(TBC1D24):c.469C>G (p.Arg157Gly)	TBC1D24	Uncertain significance	criteria provided, single submitter
392542	NM_001199107.2(TBC1D24):c.1633A>G (p.Ile545Val)	TBC1D24	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 9 · 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
TBC1D24	Strong	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 65	21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBC1D24	Orphanet:163727	Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome
TBC1D24	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
TBC1D24	Orphanet:352582	Familial infantile myoclonic epilepsy
TBC1D24	Orphanet:352587	Focal epilepsy-intellectual disability-cerebro-cerebellar malformation
TBC1D24	Orphanet:352596	Progressive myoclonic epilepsy with dystonia
TBC1D24	Orphanet:79500	DOORS syndrome
TBC1D24	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
TBC1D24	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CCNF	Orphanet:803	Amyotrophic lateral sclerosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TBC1D24	HGNC:29203	ENSG00000162065	Q9ULP9	TBC1 domain family member 24	gencc,clinvar
CCNF	HGNC:1591	ENSG00000162063	P41002	Cyclin-F	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBC1D24	TBC1 domain family member 24	May act as a GTPase-activating protein for Rab family protein(s).
CCNF	Cyclin-F	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TBC1D24	Other/Unknown	no		Rab-GAP-TBC_dom, TLDc_dom, Rab-GAP_TBC_sf
CCNF	Other/Unknown	no		F-box_dom, Cyclin_C-dom, Cyclin_N

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
middle temporal gyrus	1
parotid gland	1
hair follicle	1
olfactory bulb	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBC1D24	227	ubiquitous	marker	parotid gland, Brodmann (1909) area 23, middle temporal gyrus
CCNF	213	ubiquitous	marker	type B pancreatic cell, olfactory bulb, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCNF	6,626
TBC1D24	1,016

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCNF	P41002	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBC1D24	Q9ULP9	84.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Rab regulation of trafficking	1	184.2×	0.042	TBC1D24
TBC/RABGAPs	1	129.8×	0.042	TBC1D24
Class I MHC mediated antigen processing & presentation	1	35.0×	0.089	CCNF
Neddylation	1	23.7×	0.089	CCNF
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.089	CCNF
Membrane Trafficking	1	18.5×	0.089	TBC1D24
Vesicle-mediated transport	1	17.4×	0.089	TBC1D24
Adaptive Immune System	1	14.9×	0.091	CCNF
Post-translational protein modification	1	9.6×	0.124	CCNF
Immune System	1	6.5×	0.155	CCNF
Metabolism of proteins	1	6.2×	0.155	CCNF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
re-entry into mitotic cell cycle	1	2808.7×	0.003	CCNF
negative regulation of cellular response to oxidative stress	1	2106.5×	0.003	TBC1D24
negative regulation of centrosome duplication	1	1685.2×	0.003	CCNF
positive regulation of neuron migration	1	495.6×	0.008	TBC1D24
positive regulation of dendrite morphogenesis	1	443.5×	0.008	TBC1D24
positive regulation of excitatory postsynaptic potential	1	263.3×	0.008	TBC1D24
axon development	1	227.7×	0.008	TBC1D24
placenta development	1	221.7×	0.008	CCNF
synaptic vesicle endocytosis	1	216.1×	0.008	TBC1D24
dendrite development	1	195.9×	0.008	TBC1D24
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1	187.2×	0.008	CCNF
G1/S transition of mitotic cell cycle	1	100.3×	0.014	CCNF
cellular response to oxidative stress	1	77.3×	0.017	TBC1D24
neuron projection development	1	61.1×	0.020	TBC1D24
regulation of cell cycle	1	37.3×	0.030	CCNF
cell division	1	23.1×	0.046	CCNF
protein ubiquitination	1	20.7×	0.048	CCNF

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
TBC1D24	0	0
CCNF	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	TBC1D24, CCNF

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TBC1D24	0	—
CCNF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.