RAP1GAP2

protein-coding

RAP1 GTPase activating protein 2

Gene summary

This gene encodes a GTPase-activating protein that activates the small guanine-nucleotide-binding protein Rap1 in platelets. The protein interacts with synaptotagmin-like protein 1 and Rab27 and regulates secretion of dense granules from platelets at sites of endothelial damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Previous symbols:

GARNL4

MANE transcript

NM_015085.5

Inheritance

—

ClinVar variants

U:103B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr17:2,755,705-3,037,741

External References & Databases

Ensembl (ENSG00000132359)

Transcript & Mutation Effects

hg38 • Region Span ~282.0 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 RAP1GAP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015085.5. 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			4 clinvar	2 clinvar	1 clinvar	7
missense			90 clinvar	4 clinvar	1 clinvar	95
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	103	6	2	111

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015085.5	RefSeq	NP_055900.4	24	MANE Select
ENST00000254695.13	Ensembl	ENSP00000254695.8	24	MANE Select
NM_001100398.2	RefSeq	NP_001093868.1	23	Standard
NM_001330058.2	RefSeq	NP_001316987.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Rap1 signalling
Adaptive Immune System

Biological Process

regulation of cell size
negative regulation of neuron projection development
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity
protein binding

Cellular Component

centrosome
cytosol
plasma membrane
nuclear membrane
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254695
Coding exons: 24
Length: 260684
Individuals with no LoFs: 124625
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 124639
p: 0.0000562

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.23	307	438	0.701	0.0000270	4768
Missense (PolyPhen)		66	107.89	0.61175		1131
Synonymous	0.784	168	181	0.926	0.0000125	1370
Loss of Function	4.97	7	41.6	0.168	0.00000204	496

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000036	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. {ECO:0000269|PubMed:15632203}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.128
RVIS EVS: -1.13
RVIS percentile EVS: 6.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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