RALGDS

protein-coding

ral guanine nucleotide dissociation stimulator

Gene summary

Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes.[supplied by OMIM, Nov 2010]

MANE transcript

NM_006266.4

Inheritance

ClinVar variants

U:132B:44

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr9:133,097,720-133,149,334

External References & Databases

Ensembl (ENSG00000160271)

Transcript & Mutation Effects

hg38 • Region Span ~51.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RALGDS variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 142

not providedTotal: 32

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006266.4. 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			4 clinvar	25 clinvar	9 clinvar	38
missense			124 clinvar	9 clinvar	1 clinvar	134
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	132	34	10	176

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006266.4	RefSeq	NP_006257.1	18	MANE Select
ENST00000372050.8	Ensembl	ENSP00000361120.3	18	MANE Select
NM_001042368.3	RefSeq	NP_001035827.1	18	Standard
NM_001271774.2	RefSeq	NP_001258703.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Choline metabolism in cancer - Homo sapiens (human)
Rap1 signaling pathway - Homo sapiens (human)
Ras signaling pathway - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)

Biological Process

Ras protein signal transduction
regulation of catalytic activity

Molecular Function

guanyl-nucleotide exchange factor activity
protein binding
GTPase regulator activity

Cellular Component

nucleus
cytosol
brush border

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372050
Coding exons: 18
Length: 66195
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	424	518	0.819	0.0000339	5846
Missense (PolyPhen)		68	86.103	0.78975		981
Synonymous	-1.23	247	224	1.10	0.0000162	1869
Loss of Function	4.89	8	42.4	0.189	0.00000200	511

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulates the dissociation of GDP from the Ras-related RalA and RalB GTPases which allows GTP binding and activation of the GTPases. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap.;

Recessive Scores

pRec: 0.161

Intolerance Scores

LoFtool: 0.515
RVIS EVS: -1.34
RVIS percentile EVS: 4.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.758

Gene Damage Prediction

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