VAT1L

Chr 16

vesicle amine transport 1 like

NCBI Gene: 57687 ENSG00000171724 UniProt: Q9HCJ6 OMIM: 620202

VAT1L encodes a putative NADPH-dependent quinone oxidoreductase with oxidoreductase activity and zinc ion binding capability. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF >1), suggesting it may tolerate such changes. Currently, no well-established human diseases have been definitively linked to VAT1L mutations in the medical literature.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable oxidoreductase activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.07

Clinical Summary— VAT1L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

67 VUS of 79 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.34

OE 0.66 (0.42–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.75Z-score

OE missense 1.14 (1.03–1.26)

264 obs / 231.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.42–1.07)

0≤0.351.4

Missense OE?1.14 (1.03–1.26)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 12 / 18.1Missense obs/exp: 264 / 231.7Syn Z: -1.57

This gene — mechanism propensity

0.7132th %ile

GOF

0.74top 25%

LOF

0.2774th %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

79 submitted variants in ClinVar

ClinVar

Classification Summary

VUS67

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	67	67
Likely Benign	0	0
Benign	0	0
Total	67	67

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap VAT1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →