RGL3

protein-coding

ral guanine nucleotide dissociation stimulator like 3

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in 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_001035223.4

Inheritance

—

ClinVar variants

U:160B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.06

Max pathogenic AF

—

Genomic locus

chr19:11,384,341-11,419,328

External References & Databases

Ensembl (ENSG00000205517)

Transcript & Mutation Effects

hg38 • Region Span ~35.0 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 RGL3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 150

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001035223.4. 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			1 clinvar	1 clinvar		2
missense			144 clinvar	10 clinvar		154
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	160	11	0	171

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001035223.4	RefSeq	NP_001030300.3	19	MANE Select
ENST00000380456.8	Ensembl	ENSP00000369823.3	19	MANE Select
NM_001161616.3	RefSeq	NP_001155088.2	19	Standard
ENST00000393423.7	Ensembl	ENSP00000377075.3	19	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

Ral guanyl-nucleotide exchange factor activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393423
Coding exons: 19
Length: 35002
Individuals with no LoFs: 125232
Homozygous LoFs: 1
Heterozygous LoFs: 515
Defined: 125748
p: 0.00205

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.300	451	433	1.04	0.0000269	4526
Missense (PolyPhen)		158	147.39	1.072		1573
Synonymous	0.715	171	183	0.933	0.0000113	1512
Loss of Function	-0.347	46	43.5	1.06	0.00000271	414

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0023	0.0022	notable
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.0016	0.0016	notable
South Asian	0.0076	0.0064	notable
Other	0.0026	0.0023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for Ral-A. Potential effector of GTPase HRas and Ras-related protein M-Ras. Negatively regulates Elk-1-dependent gene induction downstream of HRas and MEKK1 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.983
RVIS EVS: -0.11
RVIS percentile EVS: 45.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.107

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High