VGLL4

Chr 3

vestigial like family member 4

Also known as: VGL-4

VGLL4 encodes a transcriptional coactivator that regulates Wnt and Hippo signaling pathways and negatively regulates cell growth. Mutations cause autosomal recessive erythrokeratoderma variabilis et progressiva, a genodermatosis characterized by persistent hyperkeratotic plaques and transient erythematous patches that can appear in infancy or childhood. The gene shows minimal constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.95
Clinical SummaryVGLL4
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 50 VUS of 93 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.073
Z-score 1.67
OE 0.37 (0.170.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.27Z-score
OE missense 0.95 (0.831.07)
176 obs / 186.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.170.95)
00.351.4
Missense OE0.95 (0.831.07)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 3 / 8.1Missense obs/exp: 176 / 186.2Syn Z: -1.60

ClinVar Variant Classifications

93 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS50
Likely Benign2
31
Pathogenic
1
Likely Pathogenic
50
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
48
2
0
50
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total04934184

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

View in ClinVar →

Protein Context — Lollipop Plot

VGLL4 · 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.

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Clinical Literature
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