RALGPS1

protein-coding

Ral GEF with PH domain and SH3 binding motif 1, the group of Pleckstrin homology domain containing

Gene summary

Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Ral protein signal transduction. Predicted to be located in cytoplasm. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

MANE transcript

NM_014636.3

Inheritance

—

ClinVar variants

U:47B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr9:126,914,774-127,223,166

External References & Databases

Ensembl (ENSG00000136828)

Transcript & Mutation Effects

hg38 • Region Span ~308.4 kb

Loading mutation effect viewer...

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 RALGPS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014636.3. 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			2 clinvar			2
missense			43 clinvar	1 clinvar		44
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	47	1	0	48

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 90 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014636.3	RefSeq	NP_055451.1	18	MANE Select
ENST00000259351.10	Ensembl	ENSP00000259351.5	18	MANE Select
NM_001190728.1	RefSeq	NP_001177657.1	17	Standard
NM_001190729.2	RefSeq	NP_001177658.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ralgps1	Danio rerio	Structure: pronephric glomerulus Quality: permeability abnormal

Gene / Model

Organism

Observed Phenotype

ralgps1

Danio rerio

Structure: pronephric glomerulus

Quality: permeability

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

small GTPase mediated signal transduction
regulation of Ral protein signal transduction
intracellular signal transduction

Molecular Function

guanyl-nucleotide exchange factor activity
Ral guanyl-nucleotide exchange factor activity

Cellular Component

cellular_component
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259351
Coding exons: 18
Length: 308393
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125722
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.09	163	318	0.512	0.0000173	3643
Missense (PolyPhen)		30	109.65	0.27361		1355
Synonymous	0.988	110	124	0.887	0.00000735	1074
Loss of Function	5.51	1	37.3	0.0268	0.00000217	399

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for the small GTPase RALA. May be involved in cytoskeletal organization (By similarity). Guanine nucleotide exchange factor for. {ECO:0000250, ECO:0000269|PubMed:10747847, ECO:0000269|PubMed:10889189}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.432
RVIS EVS: -0.29
RVIS percentile EVS: 32.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.945

Gene Damage Prediction

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