RASGRP3

protein-coding

RAS guanyl releasing protein 3, the group of EF-hand domain containing

Gene summary

The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017]

MANE transcript

NM_001139488.2

Inheritance

—

ClinVar variants

U:78B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:33,436,324-33,586,669

External References & Databases

Ensembl (ENSG00000152689)

Transcript & Mutation Effects

hg38 • Region Span ~150.3 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 RASGRP3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001139488.2. 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	1 clinvar	4
missense			74 clinvar	2 clinvar		76
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	78	5	1	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 94 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001139488.2	RefSeq	NP_001132960.1	16	MANE Select
ENST00000403687.8	Ensembl	ENSP00000384192.3	16	MANE Select
NM_001349975.2	RefSeq	NP_001336904.1	16	Standard
NM_001349976.2	RefSeq	NP_001336905.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

B cell receptor signaling pathway - Homo sapiens (human)
Rap1 signaling pathway - Homo sapiens (human)
Ras signaling pathway - Homo sapiens (human)
MAPK signaling pathway - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)

Biological Process

MAPK cascade
small GTPase mediated signal transduction
Ras protein signal transduction
positive regulation of GTPase activity

Molecular Function

guanyl-nucleotide exchange factor activity
Ras guanyl-nucleotide exchange factor activity
GTPase activator activity
calcium ion binding
protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
guanyl-nucleotide exchange factor complex
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403687
Coding exons: 16
Length: 128427
Individuals with no LoFs: 124615
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 124659
p: 0.000177

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.504	334	361	0.925	0.0000182	4536
Missense (PolyPhen)		133	151.05	0.8805		1985
Synonymous	0.315	131	136	0.966	0.00000709	1272
Loss of Function	3.72	10	33.1	0.302	0.00000152	432

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.000033	0.000033	rare
Other	0.00050	0.00050	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for Ras and Rap1. {ECO:0000269|PubMed:10934204}.;

Intolerance Scores

LoFtool: 0.685
RVIS EVS: 0.38
RVIS percentile EVS: 75.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.818

Gene Damage Prediction

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