RANGAP1

Chr 22

Ran GTPase activating protein 1

Also known as: Fug1, RANGAP, SD

NCBI Gene: 5905ENSG00000100401UniProt: P46060

This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

120
ClinVar variants
20
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— RANGAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 76 VUS of 120 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.
0.53LOEUF
pLI 0.026
Z-score 3.40
OE 0.30 (0.17–0.53)
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.
1.14Z-score
OE missense 0.83 (0.75–0.91)
281 obs / 340.1 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.0.30 (0.17–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.75–0.91)
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.1.02
0≤1.21.6
LoF obs/exp: 8 / 27.1Missense obs/exp: 281 / 340.1Syn Z: -0.16

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS76
Likely Benign5
Benign4
19
Pathogenic
1
Likely Pathogenic
76
VUS
5
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
64
12
0
76
Likely Benign
0
4
0
1
5
Benign
0
1
2
1
4
Total069342105

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

View in ClinVar →

Protein Context — Lollipop Plot

RANGAP1 · 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
The Ran GTPase-activating protein (RanGAP1) is critically involved in smooth muscle cell differentiation, proliferation and migration following vascular injury: implications for neointima formation and restenosis.
Vorpahl M et al.·PLoS One
2014
Palmdelphin Regulates Nuclear Resilience to Mechanical Stress in the Endothelium.
Sáinz-Jaspeado M et al.·Circulation
2021
Alterations in the Nucleocytoplasmic Transport in Heart Transplant Rejection.
Lozano-Edo S et al.·Transplant Proc
2021
Oncogenic potential of nucleoporins in non-hematological cancers: recent update beyond chromosome translocation and gene fusion.
Roy A et al.·J Cancer Res Clin Oncol
2019Review
Identification of cereblon-binding proteins and relationship with response and survival after IMiDs in multiple myeloma.
Zhu YX et al.·Blood
2014
Prognostic and therapeutic implications of disulfidptosis-related genes in multiple myeloma.
Zang Y et al.·Front Immunol
2025
Nuclear envelope localization of Ran-binding protein 2 and Ran-GTPase-activating protein 1 in psoriatic epidermal keratinocytes.
Yasuda K et al.·Exp Dermatol
2014
ON 01910.Na inhibits growth of diffuse large B-cell lymphoma by cytoplasmic sequestration of sumoylated C-MYB/TRAF6 complex.
Dai YH et al.·Transl Res
2016
Isolation of differentially expressed genes in NPM-ALK-positive anaplastic large cell lymphoma.
Villalva C et al.·Br J Haematol
2002
Urokinase receptor associates with myocardin to control vascular smooth muscle cells phenotype in vascular disease.
Kiyan Y et al.·Arterioscler Thromb Vasc Biol
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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