RANBP6

Chr 9

RAN binding protein 6

NCBI Gene: 26953 ENSG00000137040 UniProt: O60518

The protein functions as a nuclear transport receptor that enables nuclear import signal receptor activity and binds nuclear localization sequences to facilitate protein import into the nucleus. Currently, no established human diseases have been definitively linked to RANBP6 mutations in the medical literature. The inheritance pattern for any potential RANBP6-related disorders has not been determined.

ResearchSummary from RefSeq, UniProt

Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.60

Clinical Summary— RANBP6

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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

137 VUS of 145 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.000

Z-score 3.40

OE 0.38 (0.24–0.60)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.33Z-score

OE missense 1.04 (0.97–1.11)

594 obs / 571.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.38 (0.24–0.60)

0≤0.351.4

Missense OE?1.04 (0.97–1.11)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 13 / 34.6Missense obs/exp: 594 / 571.6Syn Z: -2.85

This gene — mechanism propensity

0.6455th %ile

GOF

0.5170th %ile

LOF

0.3161th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

VUS137

Likely Benign4

137

VUS

Likely 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	2	135	0	137
Likely Benign	0	2	2	4
Benign	0	0	0	0
Total	2	137	2	141

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

View in ClinVar →

158 pathogenic / likely-pathogenic (of 164) ClinVar copy-number / structural variants overlap RANBP6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →