RASGRF2

protein-coding

Ras protein specific guanine nucleotide releasing factor 2, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Gene summary

RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

MANE transcript

NM_006909.3

Inheritance

—

ClinVar variants

U:128B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr5:80,960,363-81,230,162

External References & Databases

Ensembl (ENSG00000113319)

Transcript & Mutation Effects

hg38 • Region Span ~269.8 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 RASGRF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006909.3. 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			3 clinvar	2 clinvar		5
missense			123 clinvar	4 clinvar		127
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	128	6	0	134

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006909.3	RefSeq	NP_008840.1	27	MANE Select
ENST00000265080.9	Ensembl	ENSP00000265080.4	27	MANE Select
ENST00000503795.1	Ensembl	ENSP00000421771.1	25	Standard
ENST00000638442.1	Ensembl	ENSP00000491428.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ras signaling pathway - Homo sapiens (human)
MAPK signaling pathway - Homo sapiens (human)
MAPK Signaling Pathway
Ras Signaling
Signaling by GPCR

Biological Process

MAPK cascade
G protein-coupled receptor signaling pathway
small GTPase mediated signal transduction
response to endoplasmic reticulum stress
regulation of Rho protein signal transduction

Molecular Function

guanyl-nucleotide exchange factor activity
Ras guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
calmodulin binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265080
Coding exons: 27
Length: 269485
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.03	480	707	0.679	0.0000395	8160
Missense (PolyPhen)		141	260.04	0.54222		3094
Synonymous	1.13	245	269	0.912	0.0000163	2354
Loss of Function	5.81	16	67.5	0.237	0.00000382	758

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00029	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation. {ECO:0000269|PubMed:15128856}.;

Intolerance Scores

LoFtool: 0.624
RVIS EVS: -1.26
RVIS percentile EVS: 5.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.716

Gene Damage Prediction

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