TBC1D10B

Chr 16

TBC1 domain family member 10B

Also known as: EPI64B, FP2461

TBC1D10B encodes a GTPase-activating protein that regulates RAB3A, RAB22A, RAB27A, and RAB35, which are essential for intracellular vesicle trafficking. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.21), indicating that mutations likely cause severe developmental phenotypes. However, no specific disease associations or inheritance patterns have been established for this gene.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.21
Clinical SummaryTBC1D10B
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.999
Z-score 4.69
OE 0.07 (0.030.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.95Z-score
OE missense 0.73 (0.660.80)
288 obs / 397.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.21)
00.351.4
Missense OE0.73 (0.660.80)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 2 / 29.5Missense obs/exp: 288 / 397.1Syn Z: 0.86
DN
0.3892th %ile
GOF
0.6639th %ile
LOF
0.69top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.21
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TBC1D10B · 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.

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Clinical Literature
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