FGD5

Chr 3

FYVE, RhoGEF and PH domain containing 5

Also known as: ZFYVE23

This protein functions as a guanine nucleotide exchange factor that activates CDC42 by facilitating GDP-to-GTP exchange, regulating actin cytoskeleton organization, cell shape, and vascular endothelial cell functions including angiogenesis. Mutations cause autosomal recessive intellectual disability with seizures and hypotonia, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.16
Clinical SummaryFGD5
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 6.46
OE 0.07 (0.030.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.17Z-score
OE missense 0.98 (0.931.04)
830 obs / 843.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.16)
00.351.4
Missense OE0.98 (0.931.04)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 4 / 56.3Missense obs/exp: 830 / 843.7Syn Z: -0.36
DN
0.3395th %ile
GOF
0.4777th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FGD5 · 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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