RANGRF

Chr 17

RAN guanine nucleotide release factor

Also known as: HSPC165, HSPC236, MOG1, RANGNRF

The protein functions as a guanine nucleotide release factor that regulates RAN-dependent mitotic spindle dynamics and enhances expression of the SCN5A cardiac sodium channel at the cell membrane. Mutations cause autosomal recessive epileptic encephalopathy with onset in early infancy, characterized by severe seizures and developmental delays. The gene shows tolerance to loss-of-function variants (low constraint), which is consistent with the recessive inheritance pattern observed in affected patients.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOEUF 1.42
Clinical SummaryRANGRF
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Gene-Disease Validity (ClinGen)
Brugada syndrome · ADRefuted

Refuted — evidence has disproved this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 120 VUS of 235 total submissions
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GeneReview available — RANGRF
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.42LOEUF
pLI 0.000
Z-score 0.62
OE 0.79 (0.461.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.06 (0.911.25)
109 obs / 102.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.79 (0.461.42)
00.351.4
Missense OE1.06 (0.911.25)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 8 / 10.1Missense obs/exp: 109 / 102.7Syn Z: 0.21

ClinVar Variant Classifications

235 submitted variants in ClinVar

Classification Summary

Pathogenic17
VUS120
Likely Benign81
Benign9
Conflicting2
17
Pathogenic
120
VUS
81
Likely Benign
9
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
0
0
0
VUS
12
87
18
3
120
Likely Benign
5
12
34
30
81
Benign
0
0
6
3
9
Conflicting
2
Total17997536229

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

View in ClinVar →

Protein Context — Lollipop Plot

RANGRF · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC