RASGEF1B

protein-coding

RasGEF domain family member 1B

Gene summary

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction. Predicted to be located in early endosome; late endosome; and midbody. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_152545.3

Inheritance

—

ClinVar variants

U:59B:6

Top phenotype

RASGEF1B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr4:81,426,393-82,044,244

External References & Databases

Ensembl (ENSG00000138670)

Transcript & Mutation Effects

hg38 • Region Span ~617.9 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 RASGEF1B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 56

RASGEF1B-related disorderTotal: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152545.3. 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			1 clinvar		1 clinvar	2
missense			55 clinvar	3 clinvar	2 clinvar	60
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	59	3	3	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152545.3	RefSeq	NP_689758.1	13	MANE Select
ENST00000264400.7	Ensembl	ENSP00000264400.2	13	MANE Select
NM_001300735.2	RefSeq	NP_001287664.1	13	Standard
NM_001300736.2	RefSeq	NP_001287665.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

small GTPase mediated signal transduction
positive regulation of GTPase activity

Molecular Function

Ras guanyl-nucleotide exchange factor activity

Cellular Component

early endosome
late endosome
midbody

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264400
Coding exons: 13
Length: 617851
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125746
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	199	267	0.746	0.0000146	3160
Missense (PolyPhen)		29	60.168	0.48199		736
Synonymous	0.197	90	92.4	0.974	0.00000521	834
Loss of Function	4.24	5	30.2	0.166	0.00000174	330

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) with specificity for RAP2A, it doesn't seems to activate other Ras family proteins (in vitro). {ECO:0000269|PubMed:19645719, ECO:0000269|PubMed:23894443}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.647
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.450

Gene Damage Prediction

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