RANGAP1

protein-coding

Ran GTPase activating protein 1, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Previous symbols:

MANE transcript

NM_002883.4

Inheritance

—

ClinVar variants

U:71B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr22:41,244,779-41,286,187

External References & Databases

Ensembl (ENSG00000100401)

Transcript & Mutation Effects

hg38 • Region Span ~41.4 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 RANGAP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002883.4. 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 clinvar	1 clinvar	3
missense			67 clinvar	4 clinvar	1 clinvar	72
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	71	5	2	78

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 209 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002883.4	RefSeq	NP_002874.1	15	MANE Select
ENST00000356244.8	Ensembl	ENSP00000348577.3	15	MANE Select
NM_001278651.2	RefSeq	NP_001265580.1	15	Standard
NM_001317930.2	RefSeq	NP_001304859.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Disease
Signal Transduction
role of ran in mitotic spindle regulation
cycling of ran in nucleocytoplasmic transport

Biological Process

signal transduction
negative regulation of protein export from nucleus
response to axon injury
activation of GTPase activity
cellular response to vasopressin

Molecular Function

RNA binding
GTPase activator activity
protein binding
Ran GTPase binding
ubiquitin protein ligase binding

Cellular Component

kinetochore
condensed chromosome kinetochore
nuclear envelope
nuclear pore
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000455915
Coding exons: 15
Length: 40641
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125748
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.14	281	340	0.826	0.0000200	3792
Missense (PolyPhen)		52	101.55	0.51207		1195
Synonymous	-0.164	153	150	1.02	0.00000983	1190
Loss of Function	3.40	8	27.1	0.295	0.00000123	342

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase activator for RAN (PubMed:8146159, PubMed:8896452, PubMed:16428860). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:8896452, PubMed:27160050). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). {ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}.;

Recessive Scores

pRec: 0.205

Intolerance Scores

LoFtool: 0.315
RVIS EVS: -0.38
RVIS percentile EVS: 28.11

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.832

Gene Damage Prediction

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