RANGRF

Chr 17

RAN guanine nucleotide release factor

Also known as: HSPC165, HSPC236, MOG1, RANGNRF

NCBI Gene: 29098 ENSG00000108961 UniProt: Q9HD47 OMIM: 607954

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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that has been shown to function as a guanine nucleotide release factor in mouse and to regulate the expression and function of the Nav1.5 cardiac sodium channel in human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 1.42

Clinical Summary— RANGRF

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Gene-Disease Validity (ClinGen)

Brugada syndrome · ADRefuted

Refuted — evidence has disproved this relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

109 VUS of 207 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RANGRF

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.62

OE 0.79 (0.46–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.06 (0.91–1.25)

109 obs / 102.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.79 (0.46–1.42)

0≤0.351.4

Missense OE?1.06 (0.91–1.25)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 8 / 10.1Missense obs/exp: 109 / 102.7Syn Z: 0.21

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

VUS109

Likely Benign81

Benign9

Conflicting2

109

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	12	88	6	3	109
Likely Benign	5	12	34	30	81
Benign	0	0	6	3	9
Conflicting	—				2
Total	17	100	46	36	201

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap RANGRF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →