RANBP2

Chr 2AD

RAN binding protein 2

Also known as: ADANE, ANE1, IIAE3, NUP358, TRP1, TRP2

RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
ADLOEUF 0.141 OMIM phenotype
Clinical SummaryRANBP2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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?
0.14LOEUF
pLI 1.000
Z-score 9.61
OE 0.09 (0.050.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
-0.78Z-score
OE missense 1.06 (1.011.10)
1662 obs / 1575.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.09 (0.050.14)
00.351.4
Missense OE?1.06 (1.011.10)
00.61.4
Synonymous OE?1.12
01.21.6
LoF obs/exp: 11 / 128.5Missense obs/exp: 1662 / 1575.3Syn Z: -2.16

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RANBP2 · 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

No active trials found for this gene.

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