RANBP1

Chr 22

RAN binding protein 1

Also known as: HTF9A

NCBI Gene: 5902 ENSG00000099901 UniProt: P43487 OMIM: 601180

This protein regulates nucleocytoplasmic transport by forming complexes with RAN GTPase and controlling the movement of proteins and nucleic acids between the nucleus and cytoplasm, and is required for normal mitotic spindle assembly. Mutations cause autosomal dominant neurodevelopmental disorder with microcephaly, seizures, and brain malformations. The gene is highly constrained against loss-of-function variants, indicating intolerance to disruption.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

LOEUF 0.47

Clinical Summary— RANBP1

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

42 VUS of 58 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.822

Z-score 2.65

OE 0.10 (0.03–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.99Z-score

OE missense 0.49 (0.39–0.60)

58 obs / 119.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.47)

0≤0.351.4

Missense OE?0.49 (0.39–0.60)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 1 / 10.1Missense obs/exp: 58 / 119.2Syn Z: -1.06

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	41	0	42
Likely Benign	0	1	2	3
Benign	0	0	1	1
Total	1	42	3	46

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

View in ClinVar →

388 pathogenic / likely-pathogenic (of 401) ClinVar copy-number / structural variants overlap RANBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →