RAP1GAP

protein-coding

RAP1 GTPase activating protein

Gene summary

This gene encodes a type of GTPase-activating-protein (GAP) that down-regulates the activity of the ras-related RAP1 protein. RAP1 acts as a molecular switch by cycling between an inactive GDP-bound form and an active GTP-bound form. The product of this gene, RAP1GAP, promotes the hydrolysis of bound GTP and hence returns RAP1 to the inactive state whereas other proteins, guanine nucleotide exchange factors (GEFs), act as RAP1 activators by facilitating the conversion of RAP1 from the GDP- to the GTP-bound form. In general, ras subfamily proteins, such as RAP1, play key roles in receptor-linked signaling pathways that control cell growth and differentiation. RAP1 plays a role in diverse processes such as cell proliferation, adhesion, differentiation, and embryogenesis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Aug 2011]

Previous symbols:

RAP1GA1

MANE transcript

NM_002885.4

Inheritance

—

ClinVar variants

U:111B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr1:21,596,221-21,669,357

External References & Databases

Ensembl (ENSG00000076864)

Transcript & Mutation Effects

hg38 • Region Span ~73.1 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 RAP1GAP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002885.4. 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			3 clinvar	2 clinvar		5
missense			91 clinvar	1 clinvar		92
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			16 clinvar			16
Total	0	0	111	3	0	114

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 187 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002885.4	RefSeq	NP_002876.2	21	MANE Select
ENST00000374765.9	Ensembl	ENSP00000363897.4	21	MANE Select
NM_001145657.3	RefSeq	NP_001139129.1	22	Standard
NM_001145658.3	RefSeq	NP_001139130.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Rap1 signaling pathway - Homo sapiens (human)
Human Thyroid Stimulating Hormone (TSH) signaling pathway
Splicing factor NOVA regulated synaptic proteins
Developmental Biology
Immune System

Biological Process

signal transduction
axon guidance
regulation of GTPase activity
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activity
GTPase activator activity
protein binding
Ras GTPase binding
protein homodimerization activity

Cellular Component

Golgi membrane
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290101
Coding exons: 24
Length: 73094
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125745
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.30	308	444	0.693	0.0000277	4714
Missense (PolyPhen)		92	159.35	0.57736		1683
Synonymous	-0.370	201	194	1.03	0.0000144	1357
Loss of Function	4.80	8	41.3	0.194	0.00000194	498

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00029	0.00028	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000037	0.000033	rare
Other	0	0.0	absent

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:15141215}.;

Recessive Scores

pRec: 0.158

Intolerance Scores

LoFtool: 0.0176
RVIS EVS: -0.73
RVIS percentile EVS: 14.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.863

Gene Damage Prediction

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