ARFGEF2

Chr 20AR

ARF guanine nucleotide exchange factor 2

Also known as: BIG2, PVNH2, dJ1164I10.1

This protein functions as a guanine nucleotide exchange factor that activates ARF proteins to regulate vesicular trafficking between the Golgi, endosomes, and plasma membrane. Biallelic mutations cause autosomal recessive periventricular heterotopia with microcephaly. The gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.251 OMIM phenotype
Clinical SummaryARFGEF2
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Gene-Disease Validity (ClinGen)
periventricular heterotopia with microcephaly, autosomal recessive · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
0.25LOEUF
pLI 1.000
Z-score 7.65
OE 0.16 (0.110.25)
Highly constrained

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

Missense Constraint
2.60Z-score
OE missense 0.76 (0.720.81)
731 obs / 957.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.16 (0.110.25)
00.351.4
Missense OE0.76 (0.720.81)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 16 / 97.5Missense obs/exp: 731 / 957.1Syn Z: 0.82

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARFGEF2 · 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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