FGD2

Chr 6

FYVE, RhoGEF and PH domain containing 2

Also known as: ZFYVE4

NCBI Gene: 221472ENSG00000146192UniProt: Q7Z6J4

The protein encoded by this gene belongs to a family of guanine nucleotide exchange factors (GEFs) which control cytoskeleton-dependent membrane rearrangements by activating the cell division cycle 42 (CDC42) protein. This gene is expressed in B lymphocytes, macrophages, and dendritic cells. The encoded protein may play a role in leukocyte signaling and vesicle trafficking in antigen-presenting cells in the immune system. [provided by RefSeq, Oct 2016]

130
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FGD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 109 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.81LOEUF
pLI 0.000
Z-score 2.46
OE 0.55 (0.38–0.81)
Tolerant

Typical tolerance to LoF variation

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.
0.70Z-score
OE missense 0.90 (0.83–0.98)
371 obs / 411.2 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.0.55 (0.38–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.83–0.98)
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.1.07
0≤1.21.6
LoF obs/exp: 19 / 34.6Missense obs/exp: 371 / 411.2Syn Z: -0.76

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS109
Likely Benign6
Benign8
6
Pathogenic
1
Likely Pathogenic
109
VUS
6
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
107
2
0
109
Likely Benign
0
3
2
1
6
Benign
0
4
0
4
8
Total0114115130

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

View in ClinVar →

Protein Context — Lollipop Plot

FGD2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Isolated glucocorticoid deficiency: Genetic causes and animal models.
Maharaj A et al.·J Steroid Biochem Mol Biol
2019Review
Epigenome-wide methylation differences in a group of lean and obese women - A HUNT Study.
Kvaløy K et al.·Sci Rep
2018
The prognostic value of faciogenital dysplasias as biomarkers in head and neck squamous cell carcinoma.
Ma C et al.·Biomark Med
2019
[Expression of RASGRP2 in Lung Adenocarcinoma and Its Effect 
on Immune Microenvironment].
Zhao S et al.·Zhongguo Fei Ai Za Zhi
2021
Sotos syndrome associated with Hirschsprung's disease: a new case and exome-sequencing analysis.
Sio CA et al.·Pediatr Res
2017Case report
[Prevalence and risk factors of gastroduodenal and biliary system diseases in infants and preschool children].
Malanicheva TG et al.·Eksp Klin Gastroenterol
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Characterization of guanine nucleotide exchange activity of DH domain of human FGD2.
Chuan J et al.·Protein Expr Purif
2020
FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles.
Huber C et al.·J Biol Chem
2008
The t-complex-encoded guanine nucleotide exchange factor Fgd2 reveals that two opposing signaling pathways promote transmission ratio distortion in the mouse.
Bauer H et al.·Genes Dev
2007Functional
Linkage of one gene for familial glucocorticoid deficiency type 2 (FGD2) to chromosome 8q and further evidence of heterogeneity.
Génin E et al.·Hum Genet
2002
Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues.
Pasteris NG et al.·Genomics
1999Functional
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