TBC1D28

Chr 17

TBC1 domain family member 28

The protein functions as a GTPase-activating protein that regulates Rab family GTPases involved in intracellular vesicle trafficking. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability, seizures, and progressive neurodegeneration. This gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

DNmechanismLOEUF 1.81
Clinical SummaryTBC1D28
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
1.81LOEUF
pLI 0.000
Z-score -0.51
OE 1.18 (0.741.81)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.28Z-score
OE missense 1.08 (0.931.25)
122 obs / 113.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.18 (0.741.81)
00.351.4
Missense OE1.08 (0.931.25)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 11 / 9.3Missense obs/exp: 122 / 113.5Syn Z: -0.52
DN
0.6938th %ile
GOF
0.4776th %ile
LOF
0.2775th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TBC1D28 · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found