TBC1D24

TBC1 domain family member 24, the group of TLDc domain containing

Basic information

Region (hg38): 16:2475051-2509671

Previous symbols: [ "DFNB86" ]

Links

ENSG00000162065 ∙ NCBI:57465 ∙ OMIM:613577 ∙ HGNC:29203 ∙ Uniprot:Q9ULP9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• DOORS syndrome (Strong), mode of inheritance: AR
• familial infantile myoclonic epilepsy (Definitive), mode of inheritance: AR
• DOORS syndrome (Definitive), mode of inheritance: AR
• DOORS syndrome (Supportive), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
• familial infantile myoclonic epilepsy (Supportive), mode of inheritance: AR
• focal epilepsy-intellectual disability-cerebro-cerebellar malformation (Supportive), mode of inheritance: AR
• progressive myoclonic epilepsy with dystonia (Supportive), mode of inheritance: AR
• DOORS syndrome (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 86 (Limited), mode of inheritance: AR
• familial infantile myoclonic epilepsy (Moderate), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss 65 (Strong), mode of inheritance: AD
• DOORS syndrome (Strong), mode of inheritance: AR
• DOORS syndrome (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 65 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, onychodystrophy, osteodystrophy, impaired intellectual development, and seizures (DOORS) syndrome; Deafness, autosomal recessive 86	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Dermatologic; Musculoskeletal; Neurologic	10741954; 20797691; 20727515; 21087195; 22211675; 23343562; 23526554; 24291220; 24387994; 24729539; 24729547; 31257402
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBC1D24 gene.

• Autosomal_dominant_nonsyndromic_hearing_loss_65 (697 variants)
• Caused_by_mutation_in_the_TBC1_domain_family,_member_24 (692 variants)
• Developmental_and_epileptic_encephalopathy,_1 (692 variants)
• not_provided (289 variants)
• Inborn_genetic_diseases (143 variants)
• not_specified (107 variants)
• Familial_infantile_myoclonic_epilepsy (77 variants)
• Developmental_and_epileptic_encephalopathy,_16 (47 variants)
• DOORS_syndrome (45 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_86 (41 variants)
• TBC1D24-related_disorder (37 variants)
• Rolandic_epilepsy-paroxysmal_exercise-induced_dystonia-writer's_cramp_syndrome (30 variants)
• Seizure (3 variants)
• Epilepsy (2 variants)
• Parkinsonian_disorder (2 variants)
• Auditory_neuropathy_spectrum_disorder (2 variants)
• Intellectual_disability (2 variants)
• Movement_disorder (2 variants)
• Global_developmental_delay (2 variants)
• Specific_learning_disability (2 variants)
• Abnormality_of_the_nervous_system (2 variants)
• Cerebellar_atrophy (2 variants)
• Rare_genetic_deafness (1 variants)
• Self-limited_epilepsy_with_centrotemporal_spikes (1 variants)
• Malignant_migrating_partial_seizures_of_infancy (1 variants)
• Epilepsy,_progressive_myoclonic,_1B (1 variants)
• developmental_delay_with_seizures (1 variants)
• Tremor (1 variants)
• Myoclonus (1 variants)
• Neurodevelopmental_delay (1 variants)
• Autosomal_dominant_epilepsy (1 variants)
• Nystagmus (1 variants)
• Periodic_paralysis (1 variants)
• Dysarthria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D24 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001199107.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	199	4	210
missense	17	36	378	22	1	454
nonsense	21	5	1			27
start loss		1	1			2
frameshift	26	6	1			33
splice donor/acceptor (+/-2bp)	3	9	1			13
Total	67	57	389	221	5

Highest pathogenic variant AF is 0.00006765505

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D24	protein_coding	protein_coding	ENST00000293970	7	30589

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-8	0.578	124772	0	78	124850	0.000312

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.757	312	352	0.886	0.0000257	3622
Missense in Polyphen		95	113.76	0.83506		1169
Synonymous	-0.993	179	163	1.10	0.0000136	1098
Loss of Function	1.14	15	20.6	0.730	9.00e-7	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000570	0.000561
Ashkenazi Jewish	0.000306	0.000298
East Asian	0.0000556	0.0000556
Finnish	0.000325	0.000325
European (Non-Finnish)	0.000416	0.000406
Middle Eastern	0.0000556	0.0000556
South Asian	0.000133	0.000131
Other	0.000829	0.000824

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:20727515, ECO:0000269|PubMed:20797691}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 16 (EIEE16) [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. {ECO:0000269|PubMed:23526554, ECO:0000269|PubMed:27541164}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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 post- lingual 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. {ECO:0000269|PubMed:24729539, ECO:0000269|PubMed:24729547}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome (DOORS) [MIM:220500]: A syndrome characterized by sensorineural deafness, mental retardation, 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. {ECO:0000269|PubMed:24291220}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:24387994}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Rab regulation of trafficking (Consensus)

Intolerance Scores

• loftool: 0.612
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.83

Haploinsufficiency Scores

• pHI: 0.160
• hipred: N
• hipred_score: 0.139
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.404

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbc1d24

Gene ontology

• Biological process: neuron projection development;positive regulation of GTPase activity;regulation of cilium assembly
• Cellular component: cytoplasm;plasma membrane;cell junction;cytoplasmic vesicle membrane;neuromuscular junction;terminal bouton
• Molecular function: GTPase activator activity;protein binding