TBC1D24

Chr 16ADAR

TBC1 domain family member 24

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

The protein functions as a GTPase-activating protein that regulates Rab small GTPases involved in membrane trafficking. Mutations cause a spectrum of disorders including developmental and epileptic encephalopathy, familial infantile myoclonic epilepsy, DOORS syndrome, and both autosomal dominant and recessive forms of deafness. The condition follows both autosomal dominant and autosomal recessive inheritance patterns, with pathogenicity resulting from disrupted membrane trafficking regulation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
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.
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ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 216 VUS of 400 total submissions
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GeneReview available — TBC1D24
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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 OE0.73 (0.491.12)
00.351.4
Missense OE0.89 (0.810.97)
00.61.4
Synonymous OE1.10
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

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.PMID:30335140

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic13
VUS216
Likely Benign114
Benign5
Conflicting6
36
Pathogenic
13
Likely Pathogenic
216
VUS
114
Likely Benign
5
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
29
1
6
0
36
Likely Pathogenic
8
4
1
0
13
VUS
2
193
16
5
216
Likely Benign
0
1
47
66
114
Benign
0
0
5
0
5
Conflicting
6
Total391997571390

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
TBC1D24.
陳雅婷 中 et al.·Dev Med Child Neurol
2023
TBC1D24.
陈雅婷 et al.·Dev Med Child Neurol
2023
Myoclonic status epilepticus in TBC1D24-related DEE.
Manokaran RK et al.·Neuropediatrics
2023
Top 5 full-text resultsSearch PubTator3 ↗