VTA1

Chr 6

vesicle trafficking 1

Also known as: 6orf55, C6orf55, DRG-1, HSPC228, LIP5, My012, SBP1

VTA1 encodes a protein that functions in the endosomal multivesicular body pathway, specifically facilitating the sorting and degradation of membrane proteins including growth factor receptors. Mutations in VTA1 cause neurodevelopmental disorders with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants, suggesting that complete loss of protein function may be required for disease manifestation.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.90
Clinical SummaryVTA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 47 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 1.85
OE 0.50 (0.290.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.31Z-score
OE missense 1.07 (0.941.21)
181 obs / 169.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.290.90)
00.351.4
Missense OE1.07 (0.941.21)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 8 / 16.0Missense obs/exp: 181 / 169.5Syn Z: -0.83
DN
0.6453th %ile
GOF
0.4972th %ile
LOF
0.2969th %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

73 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS47
Likely Benign3
13
Pathogenic
2
Likely Pathogenic
47
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
1
0
1
0
2
VUS
0
43
4
0
47
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total14519065

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

View in ClinVar →

Protein Context — Lollipop Plot

VTA1 · 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 →