TBC1D24

Chr 16ADAR

TBC1 domain family member 24

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

NCBI Gene: 57465 ENSG00000162065 UniProt: Q9ULP9 OMIM: 613577

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 65MIM #616044

Deafness, autosomal recessive 86MIM #614617

Developmental and epileptic encephalopathy 16MIM #615338

DOORS syndromeMIM #220500

Epilepsy, rolandic, with paroxysmal exercise-induce dystonia and writer's crampMIM #608105

Myoclonic epilepsy, infantile, familialMIM #605021

UniProtFamilial infantile myoclonic epilepsy

UniProtDeafness, onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — TBC1D24

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 1.14

OE 0.73 (0.49–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.76Z-score

OE missense 0.89 (0.81–0.97)

312 obs / 351.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.49–1.12)

0≤0.351.4

Missense OE?0.89 (0.81–0.97)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 15 / 20.6Missense obs/exp: 312 / 351.9Syn Z: -0.99

Background carrier burden — how many people carry a rare variant somewhere in TBC1D24?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

731 rare PASS variants

Rare truncating (LoF)

1 in 1,200

112 rare PASS variants

Rare synonymous (reference)

1 in 110

346 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TBC1D24. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 95	1 in 1,300
South Asian	~43k	1 in 57	1 in 2,500
Remaining (unassigned)	~30k	1 in 65	1 in 1,400
European (Finnish)	~27k	1 in 130	1 in 1,200
Admixed American	~22k	1 in 62	1 in 1,400
African / African American	~21k	1 in 94	1 in 1,300
East Asian	~20k	1 in 77	1 in 930
Ashkenazi Jewish	~13k	1 in 340	1 in 1,400
Middle Eastern	~2,884	1 in 58	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓