RGL4

protein-coding

ral guanine nucleotide dissociation stimulator like 4

Gene summary

This oncogene encodes a protein similar to guanine nucleotide exchange factor Ral guanine dissociation stimulator. Increased expression of this gene leads to translocation of the encoded protein to the cell membrane. The encoded protein can activate several pathways, including the Ras-Raf-MEK-ERK cascade. [provided by RefSeq, Jul 2016]

MANE transcript

NM_153615.2

Inheritance

—

ClinVar variants

U:82B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr22:23,688,136-23,699,176

External References & Databases

Ensembl (ENSG00000159496)

Transcript & Mutation Effects

hg38 • Region Span ~11.0 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 RGL4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153615.2. 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
missense			79 clinvar	3 clinvar		82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	82	4	0	86

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153615.2	RefSeq	NP_705843.1	11	MANE Select
ENST00000290691.10	Ensembl	ENSP00000290691.5	11	MANE Select
NM_001329424.3	RefSeq	NP_001316353.1	12	Standard
NM_001329425.2	RefSeq	NP_001316354.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Class A Rhodopsin-like

Biological Process

small GTPase mediated signal transduction

Molecular Function

guanyl-nucleotide exchange factor activity

Cellular Component

cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290691
Coding exons: 11
Length: 11041
Individuals with no LoFs: 125516
Homozygous LoFs: 2
Heterozygous LoFs: 230
Defined: 125748
p: 0.000923

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.276	285	272	1.05	0.0000152	3049
Missense (PolyPhen)		58	50.665	1.1448		683
Synonymous	-0.676	124	115	1.08	0.00000681	983
Loss of Function	0.436	20	22.2	0.900	0.00000103	254

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00081	0.00081	rare
Ashkenazi Jewish	0.0077	0.0077	notable
East Asian	0.00087	0.00087	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00064	0.00064	rare
South Asian	0.00088	0.00085	rare
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0571

Intolerance Scores

LoFtool: 0.948
RVIS EVS: 2.56
RVIS percentile EVS: 98.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.417

Gene Damage Prediction

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