TBC1D24

Summary

TBC1D24 (TBC1 domain family member 24, HGNC:29203) is a protein-coding gene on chromosome 16p13.3, encoding TBC1 domain family member 24 (Q9ULP9). May act as a GTPase-activating protein for Rab family protein(s).

This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 57465 — RefSeq curated summary.

At a glance

• Gene–disease (curated): DOORS syndrome (Definitive, ClinGen) — +10 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,052 total — 71 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 200
• MANE Select transcript: NM_001199107

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29203
Approved symbol	TBC1D24
Name	TBC1 domain family member 24
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1171, TLDC6, DFNA65
Ensembl gene	ENSG00000162065
Ensembl biotype	protein_coding
OMIM	613577
Entrez	57465

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000562105, ENST00000564879, ENST00000566853, ENST00000567020, ENST00000569874, ENST00000627285, ENST00000630263, ENST00000636980, ENST00000643767, ENST00000646147, ENST00000859877, ENST00000859878, ENST00000859879, ENST00000859880, ENST00000859881, ENST00000965027, ENST00000965028

RefSeq mRNA: 2 — MANE Select: NM_001199107 NM_001199107, NM_020705

CCDS: CCDS42107, CCDS55980

Canonical transcript exons

ENST00000646147 — 8 exons

Exon	Start	End
ENSE00001062417	2499835	2499930
ENSE00001062419	2499357	2499420
ENSE00001062420	2498238	2498396
ENSE00001062421	2500268	2500490
ENSE00001322435	2496034	2497113
ENSE00001539713	2475127	2475170
ENSE00001687768	2497710	2497727
ENSE00003830686	2500804	2505730

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 96.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0495 / max 82.6330, expressed in 1674 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152230	4.6992	1655
207705	0.1949	97
152231	0.1554	44

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.41	gold quality
middle temporal gyrus	UBERON:0002771	94.38	gold quality
corpus epididymis	UBERON:0004359	91.01	gold quality
cerebellar vermis	UBERON:0004720	90.69	gold quality
renal medulla	UBERON:0000362	90.61	gold quality
kidney epithelium	UBERON:0004819	90.59	gold quality
superior frontal gyrus	UBERON:0002661	89.48	gold quality
entorhinal cortex	UBERON:0002728	89.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.32	gold quality
cerebellum	UBERON:0002037	88.87	gold quality
cerebellar cortex	UBERON:0002129	88.70	gold quality
cerebellar hemisphere	UBERON:0002245	88.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.67	gold quality
primary visual cortex	UBERON:0002436	88.02	gold quality
parietal lobe	UBERON:0001872	87.16	gold quality
occipital lobe	UBERON:0002021	87.16	gold quality
postcentral gyrus	UBERON:0002581	87.13	gold quality
frontal cortex	UBERON:0001870	85.94	gold quality
neocortex	UBERON:0001950	85.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.65	gold quality
cerebral cortex	UBERON:0000956	85.47	gold quality
right frontal lobe	UBERON:0002810	85.32	gold quality
temporal lobe	UBERON:0001871	85.03	gold quality
anterior cingulate cortex	UBERON:0009835	84.94	gold quality
prefrontal cortex	UBERON:0000451	84.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.78	gold quality
endothelial cell	CL:0000115	84.01	silver quality
cortex of kidney	UBERON:0001225	84.00	gold quality
adult mammalian kidney	UBERON:0000082	83.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	19.90
E-ANND-3	yes	12.15
E-ENAD-27	yes	11.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

179 targeting TBC1D24, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 31)

• Two compound heterozygous missense mutations (D147H and A509V) in TBC1D24, a gene of unknown function, are responsible for familial infantile myoclonic epilepsy. (PMID:20727515)
• A pathogenic mutation was identified in TBC1D24. (PMID:20797691)
• Findings expand the spectrum of the TBC1D24 mutation phenotype and the transcript isoforms. (PMID:23343562)
• A TBC1D24 mutation associated with focal epilepsy, cognitive impairment and cerebro-cerebellar malformation is found in a family with a homozygous TBC1D24 mutation. (PMID:23517570)
• we describe a familial form of MMPSI due to mutation in TBC1D24, revealing a devastating epileptic phenotype associated with TBC1D24 dysfunction. (PMID:23526554)
• Mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes. (PMID:24291220)
• Novel variations in TBC1D24 do not allow prediction of functional phenotypes that might explain, at least in part, the symptoms of malignant migrating partial seizures of infancy (MMPSI). (PMID:24315024)
• Recessive alleles of TBC1D24 can cause either epilepsy or nonsyndromic deafness in human. (PMID:24387994)
• TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss. (PMID:24729539)
• that the p.Ser178Leu mutation of TBC1D24 is a probable cause for dominant, nonsyndromic hearing impairment. Identification of TBC1D24 as the stereocilia-expressing gene may shed new light on its specific function in the inner ear. (PMID:24729547)
• This report supports previous observations that mutations in TBC1D24 cause diverse phenotypes (PMID:25557349)
• mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco (PMID:26371875)
• TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death (PMID:27281533)
• TBC1D24-related epilepsy can manifest with hypotonia, developmental delays, and a variety of focal-onset seizures. (PMID:27502353)
• Here, we present a familial case of a lethal early-onset epileptic encephalopathy, associated with two novel compound heterozygous missense variants on the TBC1D24 gene, which were detected by exome sequencing (PMID:27541164)
• We identified a homozygous single base alteration, c.1415 G>A;p.G428R, in TBC1D24 gene. This mutation was found in the proband’s parents and elder sister as heterozygous. The c.1415G>A mutation has not been reported previously. The c.1415G>A was considered to be damaging by SIFT software (PMID:29176366)
• Silencing TBC1D24 inhibited MCF-7 cells growth in vitro and in vivo. TBC1D24 promoted breast carcinoma growth through the IGF1R/PI3K/AKT pathway. (PMID:29893377)
• TBC1d24-ephrinB2 interaction regulates contact inhibition of locomotion in neural crest cell migration (PMID:30154457)
• he clinical feature of TBC1D24 gene mutation related epilepsy was focal myoclonus, and tended to develop into myoclonic status epilepticus, and could be aggravated by infections, and terminated by sleep or sedation drugs. (PMID:30180405)
• eight individuals with epilepsy and developmental delay who share overlapping microdeletions at 16p13.3 including TBC1D24, ATP6V0C, and PDPK1 (PMID:30245510)
• We then further investigated TBC1D24 haploinsufficiency in vivo and demonstrate that TBC1D24 is also crucial for normal presynaptic function: genetic disruption of Tbc1d24 expression in the mouse leads to an impairment of endocytosis and an enlarged endosomal compartment in neurons with a decrease in spontaneous neurotransmission. (PMID:30335140)
• TBC1D24 regulates axonal outgrowth and membrane trafficking at the growth cone in rodent and human neurons. (PMID:30858606)
• Multifocal myoclonus, epilepsia partialis continua (EPC), and fever-induced seizures were the most prominent features of epilepsy patients with TBC1D24 mutations. The best therapeutic strategy to terminate EPC might be using chloral hydrate to induce sleep and control the infection and temperature. Hearing loss and abnormal brain MRIs might exacerbate the condition during follow-up. (PMID:31112829)
• In a Drosophila model neuronally expressing human TBC1D24, the TBC1D24G501R TLDc mutation causes activity-induced locomotion and synaptic vesicle trafficking defects, but TBC1D24R360H is benign. The phenotypes of the TBC1D24G501R mutation are consistent with oxidative stress sensitivity, rescued by antioxidants. TLDc domain mutations of TBC1D24 cause Rolandic-type focal motor epilepsy and exercise-induced dystonia. (PMID:31257402)
• TBC1D24 regulates recycling of clathrin-independent cargo proteins mediated by tubular recycling endosomes. (PMID:32475639)
• Disrupted oxidative stress resistance: A homozygous mutation in the catalytic (TLDc) domain of TBC1D24 gene associated with epileptic encephalopathy. (PMID:32663648)
• Mouse Models of Human Pathogenic Variants of TBC1D24 Associated with Non-Syndromic Deafness DFNB86 and DFNA65 and Syndromes Involving Deafness. (PMID:32987832)
• Novel variants in TBC1D24 associated with epilepsy and deafness: Report of two cases. (PMID:33063868)
• TBC1D24 emerges as an important contributor to progressive postlingual dominant hearing loss. (PMID:33986365)
• TBC1D24-related familial infantile multifocal myoclonus: Description of a new Chinese pedigree with a 20 year follow up. (PMID:35413638)
• Investigation of a novel TBC1D24 variation causing autosomal dominant non-syndromic hearing loss. (PMID:38413761)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d24	ENSDARG00000069339
mus_musculus	Tbc1d24	ENSMUSG00000036473
rattus_norvegicus	Tbc1d24	ENSRNOG00000052204
drosophila_melanogaster	sky	FBGN0032901
caenorhabditis_elegans		WBGENE00016292

Protein

Protein identifiers

TBC1 domain family member 24 — Q9ULP9 (reviewed: Q9ULP9)

All UniProt accessions (5): A0A0D9SFR5, A0A2R8Y518, Q9ULP9, H3BTP5, H3BV07

UniProt curated annotations — full annotation on UniProt →

Function. May act as a GTPase-activating protein for Rab family protein(s). Involved in neuronal projections development, probably through a negative modulation of ARF6 function. Involved in the regulation of synaptic vesicle trafficking.

Subunit / interactions. Interacts with ARF6.

Subcellular location. Cell membrane. Cytoplasm. Cytoplasmic vesicle membrane. Presynapse.

Tissue specificity. Highest expression in brain.

Disease relevance. Familial infantile myoclonic epilepsy (FIME) [MIM:605021] A subtype of idiopathic epilepsy starting in early infancy and manifesting as myoclonic seizures, febrile convulsions, and tonic-clonic seizures. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 16 (DEE16) [MIM:615338] A severe autosomal recessive neurologic disorder characterized by onset of seizures in the first weeks or months of life. Seizures can be of various types, are unresponsive to medication, last for long periods of time, and occur frequently. Affected infants show psychomotor regression or lack of psychomotor development, as well as other neurologic features such as extrapyramidal signs and hypotonia. Most die in childhood. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 65 (DFNA65) [MIM:616044] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA65 is characterized by postlingual onset of slowly progressive hearing loss in the third decade. Initially affecting the high frequencies, the hearing loss eventually affects all frequencies and results in severe to profound deafness in the seventh decade. Vestibular function is normal. The disease is caused by variants affecting the gene represented in this entry. Deafness, onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome (DOORS) [MIM:220500] A syndrome characterized by sensorineural deafness, intellectual disability, hypoplastic or absent nails, small or absent distal phalanges of hands and feet. Additional features include coarse facies, a large nose with wide nasal bridge, bulbous tip and anteverted nares, a long prominent philtrum and downturned corners of the mouth. Progressive neurological manifestations include seizures from infancy, optic atrophy, and peripheral polyneuropathy. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal recessive, 86 (DFNB86) [MIM:614617] A form of non-syndromic deafness characterized by prelingual onset of profound sensorineural hearing loss affecting all frequencies. The disease is caused by variants affecting the gene represented in this entry. Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer’s cramp (EPRPDC) [MIM:608105] An autosomal recessive neurologic disorder characterized by onset of focal seizures in infancy and exercise-induced dystonia in childhood. Clinical features include involuntary movements and difficulties with fine motor skills of the hand. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The Rab-GAP TBC domain is essential for phosphatidylinositol binding.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULP9-1	1	yes
Q9ULP9-2	2

RefSeq proteins (2): NP_001186036, NP_065756 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR006571	TLDc_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily

Pfam: PF00566, PF07534

UniProt features (33 total): sequence variant 22, binding site 5, domain 2, modified residue 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULP9-F1	84.46	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 36; 40; 238; 242; 293–297

Post-translational modifications (2): 473, 480

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 589 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_OXIDATIVE_STRESS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_SYNAPTIC_VESICLE_RECYCLING, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_CELL_CELL_SIGNALING

GO Biological Process (9): dendrite development (GO:0016358), neuron projection development (GO:0031175), cellular response to oxidative stress (GO:0034599), synaptic vesicle endocytosis (GO:0048488), positive regulation of dendrite morphogenesis (GO:0050775), axon development (GO:0061564), negative regulation of cellular response to oxidative stress (GO:1900408), positive regulation of excitatory postsynaptic potential (GO:2000463), positive regulation of neuron migration (GO:2001224)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (11): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell junction (GO:0030054), cytoplasmic vesicle membrane (GO:0030659), neuromuscular junction (GO:0031594), terminal bouton (GO:0043195), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
neuron projection development	2
synapse	2
anatomical structure development	1
neuron development	1
plasma membrane bounded cell projection organization	1
response to oxidative stress	1
cellular response to chemical stress	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
cellular response to oxidative stress	1
negative regulation of cellular process	1
regulation of cellular response to oxidative stress	1
negative regulation of response to oxidative stress	1
positive regulation of signal transduction	1
excitatory postsynaptic potential	1
modulation of excitatory postsynaptic potential	1
neuron migration	1
positive regulation of cell migration	1
regulation of neuron migration	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
axon terminus	1
presynapse	1
cytoplasm	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D24	ARF6	P26438	936
TBC1D24	NANP	Q8TBE9	691
TBC1D24	CDC16	Q13042	673
TBC1D24	RAB35	Q15286	627
TBC1D24	KCNT1	Q5JUK3	620
TBC1D24	NEU1	Q99519	616
TBC1D24	SLC25A22	Q9H936	612
TBC1D24	USP6	P35125	598
TBC1D24	PRRT2	Q7Z6L0	587
TBC1D24	SCN1A	P35498	585
TBC1D24	ARF1	P10947	567
TBC1D24	TBC1D13	Q9NVG8	551
TBC1D24	ARF4	P18085	535
TBC1D24	PCDH19	Q8TAB3	514
TBC1D24	SCN2A	Q99250	507

IntAct

26 interactions, top by confidence:

A	B	Type	Score
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
TNFAIP3	UBB	psi-mi:“MI:0914”(association)	0.530
NTRK3	FAM171A2	psi-mi:“MI:0914”(association)	0.480
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
E	MRPS31	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
OR5H1	RBFOX3	psi-mi:“MI:0914”(association)	0.350
GNG2	FAM171A2	psi-mi:“MI:0914”(association)	0.350
FGB	KIF2A	psi-mi:“MI:0914”(association)	0.350
ADAT3	ABLIM1	psi-mi:“MI:0914”(association)	0.350
ATP6V1D	AQR	psi-mi:“MI:0914”(association)	0.350
SDHD	TNNC2	psi-mi:“MI:0914”(association)	0.350
ACBD7	SRC	psi-mi:“MI:0914”(association)	0.350
GPAM	SRC	psi-mi:“MI:0914”(association)	0.350
TCEAL2	MYL9	psi-mi:“MI:0914”(association)	0.350
POU3F1	DUSP3	psi-mi:“MI:0914”(association)	0.350
DOCK3	HS6ST3	psi-mi:“MI:0914”(association)	0.350
S1PR4	TSG101	psi-mi:“MI:0914”(association)	0.350
ATP6V1D	ADD1	psi-mi:“MI:0914”(association)	0.350
ARF6	TBC1D24	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (62): TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Co-fractionation), TBC1D24 (Synthetic Growth Defect), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS)

ESM2 similar proteins: A1A5K6, A6H8I2, F1M386, F1PBJ0, F1QRX7, F1QWA8, F6UMY3, O02697, O14830, O97790, P26675, P48736, Q08CX5, Q21029, Q29RJ2, Q2KI13, Q3UUG6, Q3UYK3, Q3V3E1, Q5E9C4, Q5R8B7, Q5SVR0, Q5ZJX5, Q66K14, Q6DDI6, Q6DDZ9, Q6DEY8, Q6P6R7, Q6ZT07, Q7T2D0, Q8BGG7, Q8CHG7, Q8R5A6, Q8TC07, Q8TEU7, Q8TF42, Q8VCZ6, Q8WZA2, Q91WS7, Q95LL3

Diamond homologs: A0PJX2, A2ACG1, A5PKL1, A8KBE0, B4F6Q9, O14284, Q08952, Q0IID2, Q1LWV7, Q3UUG6, Q4KMM3, Q4V8B0, Q5ZJX5, Q5ZMS4, Q6C443, Q6CMK8, Q6DDZ9, Q6DFV7, Q6FSN5, Q6P9B6, Q755A3, Q874Z5, Q8K0P3, Q8N573, Q8NI08, Q9ULP9, Q9VIH7, A1A5K6, Q08CX5, Q29RJ2, Q9UPU7, Q3U0J8, P0CP42, P0CP43, Q4I8S2, Q5AEM5, Q5B8X6, Q6BJM5, Q6ZZF5, Q7S4P1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1052 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	71
Likely pathogenic	24
Uncertain significance	534
Likely benign	267
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100677	NM_001199107.2(TBC1D24):c.208G>T (p.Asp70Tyr)	Pathogenic
100678	NM_001199107.2(TBC1D24):c.878G>C (p.Arg293Pro)	Pathogenic
1066340	NM_001199107.2(TBC1D24):c.115G>C (p.Ala39Pro)	Pathogenic
1071941	NM_001199107.2(TBC1D24):c.642_793del (p.Trp215fs)	Pathogenic
1072207	NM_001199107.2(TBC1D24):c.715del (p.Val239fs)	Pathogenic
1203100	NM_001199107.2(TBC1D24):c.1206+2T>C	Pathogenic
1357131	NM_001199107.2(TBC1D24):c.1397del (p.Pro466fs)	Pathogenic
1369893	NM_001199107.2(TBC1D24):c.56del (p.Ile19fs)	Pathogenic
1378399	NM_001199107.2(TBC1D24):c.979A>T (p.Lys327Ter)	Pathogenic
1397090	NM_001199107.2(TBC1D24):c.1540C>T (p.Gln514Ter)	Pathogenic
1402576	NC_000016.9:g.(?2546150)(2550959_?)del	Pathogenic
1451981	NM_001199107.2(TBC1D24):c.1141dup (p.Arg381fs)	Pathogenic
1453407	NM_001199107.2(TBC1D24):c.636G>A (p.Trp212Ter)	Pathogenic
1456664	NM_001199107.2(TBC1D24):c.752del (p.Phe251fs)	Pathogenic
1459471	NM_001199107.2(TBC1D24):c.806del (p.Ile269fs)	Pathogenic
1473155	NM_001199107.2(TBC1D24):c.706G>A (p.Gly236Ser)	Pathogenic
1690348	NM_001199107.2(TBC1D24):c.535dup (p.Ser179fs)	Pathogenic
1732348	NM_001199107.2(TBC1D24):c.352del (p.Leu118fs)	Pathogenic
1737351	NM_001199107.2(TBC1D24):c.404del (p.Pro135fs)	Pathogenic
183153	NM_001199107.2(TBC1D24):c.313T>C (p.Cys105Arg)	Pathogenic
183155	NM_001199107.2(TBC1D24):c.999G>T (p.Leu333Phe)	Pathogenic
183156	NM_001199107.2(TBC1D24):c.1460dup (p.His487fs)	Pathogenic
1970211	NM_001199107.2(TBC1D24):c.668_669delinsAA (p.Cys223Ter)	Pathogenic
2035641	NM_001199107.2(TBC1D24):c.1574del (p.Gly525fs)	Pathogenic
207507	NM_001199107.2(TBC1D24):c.475del (p.Leu159fs)	Pathogenic
207516	NM_001199107.2(TBC1D24):c.691_700delinsCTT (p.Val231fs)	Pathogenic
2121170	NM_001199107.2(TBC1D24):c.1488del (p.Met497fs)	Pathogenic
2127078	NM_001199107.2(TBC1D24):c.270_286del (p.Pro91fs)	Pathogenic
2163597	NM_001199107.2(TBC1D24):c.132G>A (p.Trp44Ter)	Pathogenic
236046	NM_001199107.2(TBC1D24):c.194G>T (p.Arg65Leu)	Pathogenic

SpliceAI

2060 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2497109:AAGAG:A	donor_gain	1.0000
16:2497110:AGAG:A	donor_gain	1.0000
16:2497111:GAG:G	donor_gain	1.0000
16:2497111:GAGG:G	donor_gain	1.0000
16:2497112:AG:A	donor_gain	1.0000
16:2497112:AGGT:A	donor_loss	1.0000
16:2497113:GG:G	donor_gain	1.0000
16:2497113:GGTA:G	donor_loss	1.0000
16:2497114:G:GG	donor_gain	1.0000
16:2497114:GTAG:G	donor_loss	1.0000
16:2497115:T:A	donor_loss	1.0000
16:2498237:GGCA:G	acceptor_gain	1.0000
16:2499418:G:GT	donor_gain	1.0000
16:2500266:A:AG	acceptor_gain	1.0000
16:2500267:G:GG	acceptor_gain	1.0000
16:2500487:GTCG:G	donor_gain	1.0000
16:2500488:TCGG:T	donor_loss	1.0000
16:2500491:G:GA	donor_loss	1.0000
16:2500491:G:GG	donor_gain	1.0000
16:2500492:T:G	donor_loss	1.0000
16:2475169:AG:A	donor_loss	0.9900
16:2475170:GGT:G	donor_loss	0.9900
16:2475172:T:G	donor_loss	0.9900
16:2497683:T:G	acceptor_gain	0.9900
16:2498232:CCTCA:C	acceptor_loss	0.9900
16:2498233:CTCA:C	acceptor_loss	0.9900
16:2498233:CTCAG:C	acceptor_loss	0.9900
16:2498234:TCA:T	acceptor_loss	0.9900
16:2498235:CAGGC:C	acceptor_loss	0.9900
16:2498236:A:AC	acceptor_loss	0.9900

AlphaMissense

3678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2499905:G:A	G426E	1.000
16:2496705:T:C	L186P	0.999
16:2496782:T:A	W212R	0.999
16:2496782:T:C	W212R	0.999
16:2499842:G:A	G405D	0.999
16:2499847:T:G	Y407D	0.999
16:2499862:T:A	W412R	0.999
16:2499862:T:C	W412R	0.999
16:2499904:G:A	G426R	0.999
16:2499904:G:C	G426R	0.999
16:2499904:G:T	G426W	0.999
16:2499905:G:T	G426V	0.999
16:2499926:T:C	F433S	0.999
16:2500295:T:A	W444R	0.999
16:2500295:T:C	W444R	0.999
16:2500297:G:C	W444C	0.999
16:2500297:G:T	W444C	0.999
16:2500457:T:C	F498L	0.999
16:2500458:T:C	F498S	0.999
16:2500459:C:A	F498L	0.999
16:2500459:C:G	F498L	0.999
16:2500490:G:T	G509W	0.999
16:2500804:G:A	G509E	0.999
16:2500852:G:A	G525D	0.999
16:2500867:G:A	C530Y	0.999
16:2500868:C:G	C530W	0.999
16:2500875:T:C	F533L	0.999
16:2500876:T:C	F533S	0.999
16:2500877:C:A	F533L	0.999
16:2500877:C:G	F533L	0.999

dbSNP variants (sampled 300 via entrez): RS1000158583 (16:2485825 G>C), RS1000265459 (16:2477589 A>G), RS1000274525 (16:2497867 A>C,G), RS1000334597 (16:2500554 A>G), RS1000416240 (16:2483564 G>T), RS1000604020 (16:2502007 T>G), RS1000643337 (16:2496841 C>A,G), RS1001002223 (16:2488074 C>CCCA), RS1001038408 (16:2491854 G>A,C), RS1001141014 (16:2502479 C>T), RS1001149456 (16:2473912 C>A,G,T), RS1001193271 (16:2502223 G>A,C), RS1001264594 (16:2499170 C>G,T), RS1001390888 (16:2476166 T>G), RS1001517211 (16:2474087 G>A,C,T)

Disease associations

OMIM: gene MIM:613577 | disease phenotypes: MIM:308350, MIM:616044, MIM:220500, MIM:614617, MIM:615338, MIM:605021, MIM:608105, MIM:612437, MIM:117100

GenCC curated gene-disease

Disease	Classification	Inheritance
DOORS syndrome	Definitive	Autosomal recessive
familial infantile myoclonic epilepsy	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 86	Strong	Autosomal recessive
autosomal dominant nonsyndromic hearing loss 65	Strong	Autosomal dominant
developmental and epileptic encephalopathy, 16	Strong	Autosomal recessive
malignant migrating partial seizures of infancy	Supportive	Autosomal dominant
focal epilepsy-intellectual disability-cerebro-cerebellar malformation	Supportive	Autosomal recessive
progressive myoclonic epilepsy with dystonia	Supportive	Autosomal recessive
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive
nonsyndromic genetic hearing loss	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
DOORS syndrome	Definitive	AR
nonsyndromic genetic hearing loss	Limited	AD

Mondo (23): developmental and epileptic encephalopathy, 1 (MONDO:0010632), autosomal dominant nonsyndromic hearing loss 65 (MONDO:0014470), DOORS syndrome (MONDO:0009079), autosomal recessive nonsyndromic hearing loss 86 (MONDO:0013826), developmental and epileptic encephalopathy, 16 (MONDO:0014133), familial infantile myoclonic epilepsy (MONDO:0011506), rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome (MONDO:0011970), intellectual disability (MONDO:0001071), congenital nervous system disorder (MONDO:0002320), epilepsy, progressive myoclonic, 1B (MONDO:0012904), periodic paralysis (MONDO:0016122), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), movement disorder (MONDO:0005395), specific learning disability (MONDO:0016225), malignant migrating partial seizures of infancy (MONDO:0017385)

Orphanet (14): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Deafness-onychodystrophy syndrome (Orphanet:3231), DOORS syndrome (Orphanet:79500), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Epilepsy of infancy with migrating focal seizures (Orphanet:293181), Progressive myoclonic epilepsy with dystonia (Orphanet:352596), Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome (Orphanet:163727), Familial infantile myoclonic epilepsy (Orphanet:352582), Periodic paralysis (Orphanet:206976), Progressive myoclonic epilepsy type 1 (Orphanet:308), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Rare genetic deafness (Orphanet:96210), Specific learning disability (Orphanet:211047), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

200 total (30 of 200 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000062	Ambiguous genitalia
HP:0000079	Abnormality of the urinary system
HP:0000104	Renal agenesis
HP:0000121	Nephrocalcinosis
HP:0000126	Hydronephrosis
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000187	Broad alveolar ridges
HP:0000189	Narrow palate
HP:0000194	Open mouth
HP:0000200	Short lingual frenulum
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000269	Prominent occiput
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST012442_2	Age-related hearing impairment	6.000000e-13
GCST012442_25	Age-related hearing impairment	6.000000e-13
GCST90002396_575	Mean reticulocyte volume	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009069	Movement Disorders	C10.228.662
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D020734	Parkinsonian Disorders	C10.228.140.079.862; C10.228.662.600
D000067559	Specific Learning Disorder	C10.597.606.150.550.700; C23.888.592.604.150.550.700; F03.625.374.188.700; F03.625.562.700
C564609	Deafness, Autosomal Recessive (supp.)
C563052	Digitorenocerebral Syndrome (supp.)
C535499	Epilepsy, rolandic with paroxysmal exercise-induced dystonia and writer’s cramp (supp.)
C580334	Nonsyndromic Deafness (supp.)
C580388	Prickle1-Related Progressive Myoclonic Epilepsy with Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression, increases methylation	5
Arsenic	affects cotreatment, increases abundance, increases expression, affects methylation, decreases methylation	3
Benzo(a)pyrene	decreases expression, affects methylation	3
Estradiol	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Coumestrol	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Folic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TR69	HAP1 TBC1D24 (-) 1	Cancer cell line	Male
CVCL_TR70	HAP1 TBC1D24 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT03490487	PHASE4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	PHASE4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT06710574	PHASE4	RECRUITING	Multimodal Image Technologies Investigate the Role and Mechanism of Probiotics in Improving RBD with Parkinson’s Disease
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01838278	PHASE3	UNKNOWN	Effectiveness of Vojta Therapy in Motor Development of Preterm Children
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00001929	PHASE2	COMPLETED	Treatment of Parkinson’s Disease With Eliprodil
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00693472	PHASE2	TERMINATED	Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
NCT01385592	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491529	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of Modified Release AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491932	PHASE2	COMPLETED	Open-label, Long-term Safety Extension Study of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT04536987	PHASE2	COMPLETED	Robot Therapy for Rehabilitation of Hand Movement After Stroke
NCT04912115	PHASE2	SUSPENDED	Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia
NCT05636852	PHASE2	TERMINATED	Altropane Dose for Imaging Patients With Suspected Parkinson’s Disease
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00001663	PHASE1	COMPLETED	Treatment of Cortical Myoclonus With Repetitive Transcranial Magnetic Stimulation
NCT02589340	PHASE1	TERMINATED	Buspirone, in Combination With Amantadine, for the Treatment of Levodopa-induced Dyskinesia
NCT03065192	PHASE1	COMPLETED	Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT07232147	PHASE1	NOT_YET_RECRUITING	Clinical Research on Stem Cell Therapy for Parkinson’s Disease
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation