RGL2

protein-coding

ral guanine nucleotide dissociation stimulator like 2

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction. Predicted to act upstream of or within negative regulation of cardiac muscle cell apoptotic process; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; and regulation of Ral protein signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

RAB2L

MANE transcript

NM_004761.5

Inheritance

—

ClinVar variants

U:117B:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr6:33,291,654-33,298,942

External References & Databases

Ensembl (ENSG00000237441)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 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 RGL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004761.5. 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	1 clinvar	1 clinvar	4
missense			104 clinvar	16 clinvar	1 clinvar	121
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	117	17	2	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 77 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004761.5	RefSeq	NP_004752.1	17	MANE Select
ENST00000497454.6	Ensembl	ENSP00000420211.1	17	MANE Select
NM_001243738.2	RefSeq	NP_001230667.1	15	Standard
ENST00000425946.1	Ensembl	ENSP00000392918.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ras signaling pathway - Homo sapiens (human)
Ras Signaling

Biological Process

Ras protein signal transduction
negative regulation of cardiac muscle cell apoptotic process
positive regulation of phosphatidylinositol 3-kinase signaling
regulation of Ral protein signal transduction

Molecular Function

Ras guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000497454
Coding exons: 17
Length: 7671
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.97	351	471	0.745	0.0000292	4888
Missense (PolyPhen)		150	224.19	0.66907		2337
Synonymous	2.98	138	190	0.725	0.0000106	1765
Loss of Function	4.29	11	40.5	0.272	0.00000256	399

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00099	0.00099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00010	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable guanine nucleotide exchange factor. Putative effector of Ras and/or Rap. Associates with the GTP-bound form of Rap 1A and H-Ras in vitro (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.706
RVIS EVS: -0.69
RVIS percentile EVS: 15.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.543

Gene Damage Prediction

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