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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TBC1D20
TBC1 domain family member 20
Chromosome 20 Β· 20p13
NCBI Gene: 128637Ensembl: ENSG00000125875.16HGNC: HGNC:16133UniProt: Q96BZ9
37PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of cilium assemblyGTPase activator activityprotein bindingsmall GTPase bindingMicro syndromeneurodegenerative diseaseWarburg micro syndromeIntellectual disability
✦AI Summary

TBC1D20 is a GTPase-activating protein (GAP) with multi-functional roles in cellular homeostasis. Its primary function involves accelerating GTP hydrolysis of Rab small GTPases, particularly Rab1, Rab2, and Rab18, by over five orders of magnitude 1. TBC1D20 promotes RAB18 dissociation from endoplasmic reticulum membranes into the cytosol 2 and has recently been identified as a GAP for Rab11, coordinating vesicle transport and actin remodeling during ciliogenesis 3. Mechanistically, TBC1D20 regulates autophagosome maturation through its RAB1B GAP activity, maintaining autophagic flux essential for protein and organelle degradation 4. It also facilitates lipid droplet homeostasis by promoting DGAT2 redistribution from the ER to lipid droplet surfaces via Rab1b 5. Loss-of-function TBC1D20 mutations cause Warburg Micro Syndrome 4, a rare autosomal-recessive disorder characterized by congenital cataracts, intellectual disability, and abnormal sexual development 6. TBC1D20-deficient mice exhibit cataracts, male infertility, and disrupted acrosomal development 7. The syndrome also presents with neuronal autophagic dysfunction, leading to adult-onset motor deficits 4. Clinically, TBC1D20 dysfunction represents part of a broader class of autophagy-related neurodevelopmental disorders with overlapping multisystem manifestations 8, establishing TBC1D20 as critical for maintaining lens transparency, reproductive function, and neuronal homeostasis.

Sources cited
1
TBC1D20 accelerates GTP hydrolysis of Rab1 and Rab2 by over five orders of magnitude
PMID: 23236136
2
TBC1D20 shows GAP activity for RAB18 and promotes RAB18 dissociation from ER membrane
PMID: 26063829
3
TBC1D20 is a Rab11 GAP coordinating vesicle transport and actin remodeling during ciliogenesis
PMID: 39868814
4
TBC1D20 regulates autophagosome maturation through RAB1B GAP function and maintains autophagic flux
PMID: 27487390
5
TBC1D20 mutations in Warburg Micro syndrome mice alter LD metabolism and DGAT2 redistribution
PMID: 38809969
6
TBC1D20 loss-of-function mutations cause Warburg Micro Syndrome 4 with cataracts and male infertility
PMID: 24239381
7
TBC1D20 disruption causes cataracts and testicular abnormalities including disrupted acrosomal development
PMID: 25476608
8
TBC1D20 deficiency is associated with autophagy-related neurodevelopmental and neurodegenerative disorders
PMID: 34130600
Disease Associationsβ“˜21
Micro syndromeOpen Targets
0.76Strong
neurodegenerative diseaseOpen Targets
0.52Moderate
Warburg micro syndromeOpen Targets
0.38Weak
HepatitisOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.37Weak
developmental disabilityOpen Targets
0.37Weak
genetic disorderOpen Targets
0.34Weak
lysosomal storage diseaseOpen Targets
0.22Weak
SeizureOpen Targets
0.18Weak
azoospermiaOpen Targets
0.09Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.07Suggestive
spermatogenic failure 65Open Targets
0.07Suggestive
spermatogenic failure 84Open Targets
0.07Suggestive
spermatogenic failure 93Open Targets
0.07Suggestive
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
spermatogenic failure 61Open Targets
0.07Suggestive
spermatogenic failure 62Open Targets
0.07Suggestive
spermatogenic failure 88Open Targets
0.07Suggestive
Warburg micro syndrome 4UniProt
Pathogenic Variants7
NM_144628.4(TBC1D20):c.474C>T (p.Gly158=)Pathogenic
Warburg micro syndrome 4
β˜…β˜†β˜†β˜†2025β†’ Residue 158
NM_144628.4(TBC1D20):c.627-1G>CLikely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2021
NM_144628.4(TBC1D20):c.292C>T (p.Gln98Ter)Pathogenic
Warburg micro syndrome 4
β˜†β˜†β˜†β˜†2013β†’ Residue 98
NM_144628.4(TBC1D20):c.672G>A (p.Trp224Ter)Pathogenic
Warburg micro syndrome 4
β˜†β˜†β˜†β˜†2013β†’ Residue 224
NM_144628.4(TBC1D20):c.(70+1_71-1)_(*3107+1_?)delPathogenic
Warburg micro syndrome 4
β˜†β˜†β˜†β˜†2013
NM_144628.4(TBC1D20):c.352_353del (p.Gln118fs)Pathogenic
Warburg micro syndrome 4
β˜†β˜†β˜†β˜†2013β†’ Residue 118
NM_144628.4(TBC1D20):c.199C>T (p.Arg67Ter)Pathogenic
Warburg micro syndrome 4
β˜†β˜†β˜†β˜†2013β†’ Residue 67
View on ClinVar β†—
Related Genes
RAB1BProtein interaction100%USP6Protein interaction90%CDC16Protein interaction88%RAB18Protein interaction79%TBC1D23Protein interaction71%RAB1AProtein interaction70%
Tissue Expression6 tissues
Lung
100%
Ovary
86%
Bone Marrow
80%
Heart
76%
Liver
71%
Brain
58%
Gene Interaction Network
Click a node to explore
TBC1D20RAB1BUSP6CDC16RAB18TBC1D23RAB1A
PROTEIN STRUCTURE
Preparing viewer…
PDB4HL4 Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.47Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.29 [0.18–0.47]
RankingsWhere TBC1D20 stands among ~20K protein-coding genes
  • #10,707of 20,598
    Most Researched37
  • #3,238of 5,498
    Most Pathogenic Variants7
  • #2,682of 17,882
    Most Constrained (LOEUF)0.47 Β· top quartile
Genes detectedTBC1D20
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
PMID: 34130600
Autophagy Β· 2022
1.00
2
Rab1b facilitates lipid droplet growth by ER-to-lipid droplet targeting of DGAT2.
PMID: 38809969
Sci Adv Β· 2024
0.90
3
TBC1D20 coordinates vesicle transport and actin remodeling to regulate ciliogenesis.
PMID: 39868814
J Cell Biol Β· 2025
0.80
4
Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation.
PMID: 26063829
Open Biol Β· 2015
0.70
5
Targeted disruption of Tbc1d20 with zinc-finger nucleases causes cataracts and testicular abnormalities in mice.
PMID: 25476608
BMC Genet Β· 2014
0.60