TBC1D24

Chr 16ADAR

TBC1 domain family member 24

Also known as: DEE16, DFNA65, DFNB86, DOORS, EIEE16, EIM, EPRPDC, FIME

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. [provided by RefSeq, Feb 2011]

OMIMResearchGenerating clinical summary…
LOFmechanismAD/ARLOEUF 1.126 OMIM phenotypes
Clinical SummaryTBC1D24
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Gene-Disease Validity (ClinGen)
DOORS syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.12LOEUF
pLI 0.000
Z-score 1.14
OE 0.73 (0.491.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.76Z-score
OE missense 0.89 (0.810.97)
312 obs / 351.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.73 (0.491.12)
00.351.4
Missense OE?0.89 (0.810.97)
00.61.4
Synonymous OE?1.10
01.21.6
LoF obs/exp: 15 / 20.6Missense obs/exp: 312 / 351.9Syn Z: -0.99
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTBC1D24-related DOORS syndromeLOFAR
definitiveTBC1D24-related myoclonic epilepsy, infantile, familialOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4785th %ile
GOF
0.5464th %ile
LOF
0.3941th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFImportantly, heterozygous TBC1D24 mutation carriers have also been reported with seizures, suggesting that haploinsufficiency for TBC1D24 is significant clinically.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

  1. 1.PMID 30335140

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TBC1D24 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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