RAP1GDS1
Chr 4ARRap1 GTPase-GDP dissociation stimulator 1
Also known as: GDS1, SmgGDS
The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]
Primary Disease Associations & Inheritance
Alfadhel syndromeMIM #620655
AR
0
Active trials
16
Pathogenic / LP
102
ClinVar variants
1
Pubs (1 yr)
1.1
Missense Z
0.34
LOEUF· LoF intolerant
Clinical Summary— RAP1GDS1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
16 Pathogenic / Likely Pathogenic· 79 VUS of 102 total submissions
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.933
Z-score 4.29
OE 0.16 (0.08–0.34)
Highly LoF-intolerant (top ~10% of genes)
Missense Constraint
1.07Z-score
OE missense 0.83 (0.75–0.92)
252 obs / 304.6 exp
Mild missense constraint
Observed / Expected Ratios
LoF OE0.16 (0.08–0.34)
0≤0.351.4
Missense OE0.83 (0.75–0.92)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 5 / 30.6Missense obs/exp: 252 / 304.6Syn Z: 0.93
ClinVar Variant Classifications
102 submitted variants in ClinVar
Classification Summary
Pathogenic14
Likely Pathogenic2
VUS79
Likely Benign6
Benign1
14
Pathogenic
2
Likely Pathogenic
79
VUS
6
Likely Benign
1
Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 0 | 12 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 2 | 67 | 10 | 0 | 79 |
Likely Benign | 0 | 1 | 3 | 2 | 6 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 4 | 68 | 27 | 3 | 102 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →RAP1GDS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from 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
Investigation of single nucleotide polymorphisms in differentially expressed genes and proteins reveals the genetic basis of skeletal muscle growth differences between Tibetan and Large White pigs
Xiong H et al.·Anim Biosci
2024
Nsp2 has the potential to be a drug target revealed by global identification of SARS-CoV-2 Nsp2-interacting proteins.
Zheng YX et al.·Acta Biochim Biophys Sin (Shanghai)
2021
The temporal protein signature analyses of developing human deciduous molar tooth germ.
Chen X et al.·Proteomics
2024
SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families
Brandt AC et al.·Front Mol Biosci
2021
A Proteomic Investigation to Discover Candidate Proteins Involved in Novel Mechanisms of 5-Fluorouracil Resistance in Colorectal Cancer
Ortega Duran M et al.·Cells
2024Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders.
Bertoli-Avella AM et al.·Genet Med
2021
Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay.
Asiri A et al.·Ann Clin Transl Neurol
2020
The molecular profile of gastric intraepithelial foveolar type neoplasia based on somatic copy number alterations and multiple mutation analysis.
Sugai T et al.·Gastric Cancer
2024
Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.
Brandt AC et al.·Proc Natl Acad Sci U S A
2020
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age.
Xiong Y et al.·Commun Biol
2023Open Access
Microgravity simulation activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis during vasculogenesis.
Wang S et al.·Stem Cell Res
2017
Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1.
Hsieh YF et al.·PLoS One
2013Open Access
Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia.
Cimino G et al.·Haematologica
2001
Top 5 resultsSearch Europe PMC ↗
External Resources
Links to major genomics databases and tools