TBC1D13

Chr 9

TBC1 domain family member 13

NCBI Gene: 54662ENSG00000107021UniProt: Q9NVG8OMIM: 616218

TBC1D13 encodes a GTPase-activating protein that regulates RAB35 and is involved in intracellular protein transport, including insulin-induced glucose transporter translocation to the plasma membrane. The gene has low constraint against loss-of-function variants (pLI 0.0007, LOEUF 0.725), and the predicted mechanism of pathogenicity is gain-of-function. No specific disease associations are established in the provided data.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 0.72
Clinical Summary— TBC1D13
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 56 VUS of 106 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.001
Z-score 2.52
OE 0.42 (0.25–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.79Z-score
OE missense 0.67 (0.59–0.76)
155 obs / 231.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.25–0.72)
0≤0.351.4
Missense OE0.67 (0.59–0.76)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 9 / 21.7Missense obs/exp: 155 / 231.8Syn Z: 0.54
DN
0.7034th %ile
GOF
0.72top 25%
LOF
0.2386th %ile

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

GOFprediction above median
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

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS56
32
Pathogenic
1
Likely Pathogenic
56
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
0
47
9
0
56
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04742089

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

View in ClinVar →

Protein Context — Lollipop Plot

TBC1D13 · 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

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
Genome-wide admixture and association analysis identifies African ancestry specific risk loci of eosinophilic esophagitis in African American
Gautam Y et al.·J Allergy Clin Immunol
2022
Separation of powers: A key feature underlying the neuroprotective role of Retromer in age-related neurodegenerative disease?
Collins BM et al.·Curr Opin Cell Biol
2025
Editorial: Pharmacogenomics and pharmacomicrobiomics in type 2 diabetes mellitus (T2DM)
Luo JQ et al.·Front Endocrinol (Lausanne)
2023
Tandem mass tag-based proteomic profiling revealed potential therapeutic targets and mechanisms of liraglutide for the treatment of impaired glucose tolerance
Guo Q et al.·Front Endocrinol (Lausanne)
2022Functional
Insight into the Candidate Genes and Enriched Pathways Associated with Height, Length, Length to Height Ratio and Body-Weight of Korean Indigenous Breed, Jindo Dog Using Gene Set Enrichment-Based GWAS Analysis
Sheet S et al.·Animals (Basel)
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients