RASGEF1A

protein-coding

RasGEF domain family member 1A

Gene summary

Enables guanyl-nucleotide exchange factor activity. Involved in cell migration and positive regulation of Ras protein signal transduction. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_145313.4

Inheritance

—

ClinVar variants

U:52B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr10:43,194,535-43,267,065

External References & Databases

Ensembl (ENSG00000198915)

Transcript & Mutation Effects

hg38 • Region Span ~72.5 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 RASGEF1A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145313.4. 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			2 clinvar			2
missense			44 clinvar	1 clinvar		45
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	52	1	0	53

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145313.4	RefSeq	NP_660356.2	12	MANE Select
ENST00000395810.6	Ensembl	ENSP00000379155.1	12	MANE Select
NM_001282862.2	RefSeq	NP_001269791.1	13	Standard
ENST00000374455.2	Ensembl	ENSP00000363579.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrated Breast Cancer Pathway
Signal Transduction
RAF/MAP kinase cascade
MAPK1/MAPK3 signaling
MAPK family signaling cascades

Biological Process

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

Molecular Function

Ras guanyl-nucleotide exchange factor activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395809
Coding exons: 12
Length: 72385
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125715
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.66	160	287	0.558	0.0000165	3200
Missense (PolyPhen)		16	60.443	0.26471		748
Synonymous	0.131	117	119	0.985	0.00000755	886
Loss of Function	4.03	3	24.5	0.122	0.00000121	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) with specificity for RAP2A, KRAS, HRAS, and NRAS (in vitro). Plays a role in cell migration. {ECO:0000269|PubMed:17121879, ECO:0000269|PubMed:19645719}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.224
RVIS EVS: 0.08
RVIS percentile EVS: 60.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.302

Gene Damage Prediction

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