RANBP3

protein-coding

RAN binding protein 3

Gene summary

This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007322.3

Inheritance

—

ClinVar variants

U:81B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr19:5,916,139-5,978,142

External References & Databases

Ensembl (ENSG00000031823)

Transcript & Mutation Effects

hg38 • Region Span ~62.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RANBP3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007322.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			76 clinvar	1 clinvar	1 clinvar	78
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	81	1	1	83

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 75 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007322.3	RefSeq	NP_015561.1	17	MANE Select
ENST00000340578.10	Ensembl	ENSP00000341483.5	17	MANE Select
NM_001300865.2	RefSeq	NP_001287794.1	16	Standard
NM_003624.3	RefSeq	NP_003615.2	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HTLV-I infection - Homo sapiens (human)
WNT-Ncore
Canonical Wnt signaling pathway

Biological Process

protein export from nucleus
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding
Ran GTPase binding
R-SMAD binding

Cellular Component

nucleus
nuclear pore
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340578
Coding exons: 17
Length: 62004
Individuals with no LoFs: 122341
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 122342
p: 0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.85	258	356	0.724	0.0000221	3679
Missense (PolyPhen)		74	129.73	0.5704		1325
Synonymous	-0.626	170	160	1.06	0.0000121	1118
Loss of Function	5.22	1	33.7	0.0297	0.00000169	382

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000091	0.0000091	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP prevents binding of XPO1/CRM1 to the nuclear pore complex. Binds to CHC1/RCC1 and increases the guanine nucleotide exchange activity of CHC1/RCC1. Recruits XPO1/CRM1 to CHC1/RCC1 in a Ran-dependent manner. Negative regulator of TGF- beta signaling through interaction with the R-SMAD proteins, SMAD2 and SMAD3, and mediating their nuclear export. {ECO:0000269|PubMed:11425870, ECO:0000269|PubMed:11571268, ECO:0000269|PubMed:11932251, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9637251}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.0273
RVIS EVS: -0.73
RVIS percentile EVS: 14.08

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.992

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium