TBC1D20

Chr 20

TBC1 domain family member 20

Also known as: C20orf140, WARBM4

NCBI Gene: 128637ENSG00000125875UniProt: Q96BZ9

This gene encodes a protein that belongs to a family of GTPase activator proteins of Rab-like small GTPases. The encoded protein and its cognate GTPase, Rab1, bind the nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) to mediate viral replication. Depletion of this protein inhibits replication of the virus and HCV infection. Mutations in this gene are associated with Warburg micro syndrome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

Primary Disease Associations & Inheritance

UniProtWarburg micro syndrome 4
268
ClinVar variants
59
Pathogenic / LP
0.93
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TBC1D20
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
59 Pathogenic / Likely Pathogenic· 107 VUS of 268 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.36LOEUF
pLI 0.931
Z-score 3.41
OE 0.12 (0.05–0.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.21Z-score
OE missense 0.77 (0.68–0.88)
176 obs / 227.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.05–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.68–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 2 / 17.3Missense obs/exp: 176 / 227.6Syn Z: 0.74

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic10
VUS107
Likely Benign79
Benign22
Conflicting1
49
Pathogenic
10
Likely Pathogenic
107
VUS
79
Likely Benign
22
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
47
1
49
Likely Pathogenic
1
0
9
0
10
VUS
0
72
35
0
107
Likely Benign
0
1
46
32
79
Benign
0
2
18
2
22
Conflicting
—1
Total27515535268

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

View in ClinVar →

Protein Context — Lollipop Plot

TBC1D20 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TBC1D20-related Warburg micro syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — TBC1D20
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
Targeted disruption of Tbc1d20 with zinc-finger nucleases causes cataracts and testicular abnormalities in mice.
Park AK et al.·BMC Genet
2014
Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran.
Hozhabri H et al.·Am J Med Genet A
2020Case report
Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights.
Abdel-Hamid MS et al.·Clin Genet
2020Review
Deletion 1q43-44 in a patient with clinical diagnosis of Warburg-Micro syndrome.
Arroyo-Carrera I et al.·Am J Med Genet A
2015Case report
RECURRENT RAB3GAP1 MUTATIONS IN THE TURKISH POPULATION.
Tasdemir S et al.·Genet Couns
2015Case report
Large homozygous RAB3GAP1 gene microdeletion causes Warburg micro syndrome 1.
Picker-Minh S et al.·Orphanet J Rare Dis
2014Case report
Case report of four siblings in southeast Turkey with a novel RAB3GAP2 splice site mutation: Warburg micro syndrome or Martsolf syndrome?
Gumus E·Ophthalmic Genet
2018Case report
Warburg Micro Syndrome 1 due to Segmental Paternal Uniparental Isodisomy of Chromosome 2 Detected by Whole-Exome Sequencing and Homozygosity Mapping.
Sezer A et al.·Cytogenet Genome Res
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools