RAPGEFL1

Chr 17

Rap guanine nucleotide exchange factor like 1

Also known as: Link-GEFII

NCBI Gene: 51195ENSG00000108352UniProt: Q9UHV5

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
8
Pathogenic / LP
58
ClinVar variants
6
Pubs (1 yr)
1.8
Missense Z
0.46
LOEUF
Clinical Summary— RAPGEFL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 48 VUS of 58 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.297
Z-score 3.60
OE 0.23 (0.13–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.76Z-score
OE missense 0.70 (0.62–0.79)
186 obs / 266.9 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.0.23 (0.13–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.62–0.79)
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.0.94
0≤1.21.6
LoF obs/exp: 6 / 25.7Missense obs/exp: 186 / 266.9Syn Z: 0.51
DN
0.5574th %ile
GOF
0.7126th %ile
LOF
0.4038th %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

58 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS48
Likely Benign2
8
Pathogenic
48
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
46
2
0
48
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total04710158

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

View in ClinVar →

Protein Context — Lollipop Plot

RAPGEFL1 · 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
Landmark / reviewRecent case evidence
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
Screening pathogenic genes in oral squamous cell carcinoma based on the mRNA expression microarray data.
Ding Y et al.·Int J Mol Med
2018
TEAD3 + high-risk melanoma cells crosstalk with GAS6 + macrophages via the GAS6-TYRO3 ligand-receptor axis to modulate propionate metabolism and drive melanoma progression.
Fang Y et al.·J Exp Clin Cancer Res
2025
Molecular Subtypes of Balanopreputial and Urethral Male Genital Lichen Sclerosus: Distinct Transcriptomic and Clinicopathological Profiles.
Xiu X et al.·Lab Invest
2025
A novel long non-coding RNA, PICSAR, promotes thyroid cancer progression through the hsa-miR-320A/hsa-miR-485/RAPGEFL1 axis.
Hejazi M et al.·Med Oncol
2025
Molecular crosstalk between MASLD and IVDD revealed through integrated biomarker discovery analysis.
Wang G et al.·Front Immunol
2026
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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