ARHGEF16

Chr 1

Rho guanine nucleotide exchange factor 16

Also known as: GEF16, NBR

NCBI Gene: 27237ENSG00000130762UniProt: Q5VV41

The protein functions as a guanyl-nucleotide exchange factor that stimulates GDP-to-GTP exchange in RHOG GTPase and may activate RAC1 and CDC42, playing a role in chemotactic cell migration. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities. The gene is extremely intolerant to loss-of-function variants, indicating it is highly constrained and essential for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
102
P/LP submissions
0%
P/LP missense
1.02
LOEUF
GOF
Mechanism· predicted
Clinical Summary— ARHGEF16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
97 unique Pathogenic / Likely Pathogenic· 126 VUS of 260 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.47
OE 0.72 (0.52–1.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.46Z-score
OE missense 0.94 (0.86–1.02)
411 obs / 437.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.52–1.02)
0≤0.351.4
Missense OE0.94 (0.86–1.02)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 24 / 33.1Missense obs/exp: 411 / 437.9Syn Z: -0.34
DN
0.5967th %ile
GOF
0.6737th %ile
LOF
0.3940th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

260 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic95
Likely Pathogenic2
VUS126
Likely Benign10
Benign4
95
Pathogenic
2
Likely Pathogenic
126
VUS
10
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
95
0
95
Likely Pathogenic
0
0
2
0
2
VUS
0
111
15
0
126
Likely Benign
0
6
1
3
10
Benign
0
1
2
1
4
Total01181154237

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGEF16 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients