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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TBC1D14
TBC1 domain family member 14
Chromosome 4 · 4p16.1
NCBI Gene: 57533Ensembl: ENSG00000132405.19HGNC: HGNC:29246UniProt: B9A071
26PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of cilium assemblyprotein kinase bindingnegative regulation of autophagyrecycling endosome to Golgi transportThrombocytopenianeurodegenerative diseasecrush injuryCrohn's disease
✦AI Summary

TBC1D14 is a Rab GTPase-activating protein that serves as a negative regulator of autophagy by controlling membrane trafficking from recycling endosomes to autophagosomes 1. The protein localizes to Rab11-positive recycling endosomes and interacts with the autophagy kinase ULK1, where it regulates the early stages of autophagosome formation 1. Mechanistically, TBC1D14 functions through its interaction with the TRAPPIII complex, a multi-subunit tethering complex that acts as a GEF for RAB1, to maintain constitutive trafficking from peripheral recycling endosomes to the early Golgi apparatus 2. This trafficking pathway is essential for maintaining the cycling pool of ATG9 protein required for autophagy initiation 2. During amino acid starvation, TBC1D14 relocalizes from recycling endosomes to the Golgi complex, allowing transferrin receptor-positive membranes to contribute to forming autophagosomes 1. Beyond autophagy regulation, TBC1D14 has disease relevance in head and neck squamous cell carcinoma, where it suppresses lymph node metastasis by promoting DDX31 degradation and inhibiting ribosome biogenesis 3. Clinically, genetic variants in TBC1D14 have been associated with antibody response to oral cholera vaccine, suggesting broader immunological functions 4.

Sources cited
1
TBC1D14 is a negative regulator of autophagy that localizes to recycling endosomes and interacts with ULK1
PMID: 22613832
2
TBC1D14 interacts with TRAPPIII complex to regulate trafficking from recycling endosomes to Golgi and maintain ATG9 cycling
PMID: 26711178
3
TBC1D14 relocalizes during starvation allowing transferrin receptor membranes to contribute to autophagosome formation
PMID: 22613832
4
TBC1D14 suppresses lymph node metastasis in head and neck cancer by promoting DDX31 degradation
PMID: 40784392
5
TBC1D14 genetic variants are associated with antibody response to oral cholera vaccine
PMID: 37699782
Disease Associationsⓘ20
ThrombocytopeniaOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.30Weak
crush injuryOpen Targets
0.28Weak
Crohn's diseaseOpen Targets
0.28Weak
acute tonsillitisOpen Targets
0.16Weak
diaphragm diseaseOpen Targets
0.13Weak
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
Laurence-Moon syndromeOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
Abruptio PlacentaeOpen Targets
0.02Suggestive
alcohol withdrawalOpen Targets
0.02Suggestive
sign or symptomOpen Targets
0.02Suggestive
Abnormal pupillary functionOpen Targets
0.02Suggestive
joint diseaseOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
kidney oncocytomaOpen Targets
0.01Suggestive
pachyonychia congenitaOpen Targets
0.01Suggestive
triple-negative breast cancerOpen Targets
0.01Suggestive
chromophobe renal cell carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRAPPC11Protein interaction100%TRAPPC5Protein interaction100%TRAPPC6BProtein interaction100%TRAPPC13Protein interaction100%TRAPPC8Protein interaction95%TRAPPC12Protein interaction95%
Tissue Expression6 tissues
Brain
100%
Heart
74%
Lung
39%
Bone Marrow
39%
Ovary
31%
Liver
26%
Gene Interaction Network
Click a node to explore
TBC1D14TRAPPC11TRAPPC5TRAPPC6BTRAPPC13TRAPPC8TRAPPC12
PROTEIN STRUCTURE
Preparing viewer…
PDB2QQ8 · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.43Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.30 [0.21–0.43]
RankingsWhere TBC1D14 stands among ~20K protein-coding genes
  • #12,895of 20,598
    Most Researched26
  • #2,331of 17,882
    Most Constrained (LOEUF)0.43 · top quartile
Genes detectedTBC1D14
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells.
PMID: 30957628
Autophagy · 2019
1.00
2
Rabs and GAPs in starvation-induced autophagy.
PMID: 27669114
Small GTPases · 2016
0.90
3
TBC1D14 inhibits ribosome biogenesis to reduce lymph node metastasis in head and neck squamous cell carcinoma by mediating DDX31 ubiquitination.
PMID: 40784392
Int J Biol Macromol · 2025
0.80
4
TBC1D14 sets the TRAPP for ATG9.
PMID: 27171758
Autophagy · 2016
0.70
5
TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic.
PMID: 26711178
EMBO J · 2016
0.60