RASAL3

protein-coding

RAS protein activator like 3, the group of C2 and RasGAP domain containing

Gene summary

This gene belongs to the Ras GTPase-activating proteins (RasGAP) family and encodes a protein with pleckstrin homology (PH), C2, and Ras GTPase-activation protein (RasGAP) domains. This protein is localized near or at the plasma membrane when expressed exogenously. Reduced expression of this gene in some cell lines resulted in increased levels of the active form of Ras (Ras-GTP), suggesting that this gene may play a role in negatively regulating the Ras signaling pathway. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

MANE transcript

NM_022904.3

Inheritance

—

ClinVar variants

U:174B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr19:15,451,624-15,464,544

External References & Databases

Ensembl (ENSG00000105122)

Transcript & Mutation Effects

hg38 • Region Span ~12.9 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 RASAL3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 174

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022904.3. 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			4 clinvar	2 clinvar		6
missense			166 clinvar	10 clinvar		176
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	174	12	0	186

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022904.3	RefSeq	NP_075055.1	17	MANE Select
ENST00000343625.12	Ensembl	ENSP00000341905.5	17	MANE Select
NM_001348027.2	RefSeq	NP_001334956.1	10	Standard
NM_001348028.2	RefSeq	NP_001334957.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ras signaling pathway - Homo sapiens (human)
Ras Signaling
Signal Transduction
Regulation of RAS by GAPs
RAF/MAP kinase cascade

Biological Process

MAPK cascade
positive regulation of GTPase activity
negative regulation of Ras protein signal transduction
positive regulation of NK T cell proliferation

Molecular Function

GTPase activator activity

Cellular Component

cytoplasm
cytosol
cell cortex
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343625
Coding exons: 17
Length: 12948
Individuals with no LoFs: 124565
Homozygous LoFs: 0
Heterozygous LoFs: 116
Defined: 124681
p: 0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	434	539	0.806	0.0000326	6272
Missense (PolyPhen)		118	165.87	0.7114		2006
Synonymous	2.19	181	222	0.814	0.0000127	2234
Loss of Function	2.68	23	41.7	0.552	0.00000239	444

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00019	rare
Latino/Admixed American	0.000034	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00017	rare
Finnish	0.0025	0.0024	notable
European (Non-Finnish)	0.00042	0.00042	rare
South Asian	0.00037	0.00013	rare
Other	0.0012	0.0012	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway. {ECO:0000250|UniProtKB:Q8C2K5}.;

Intolerance Scores

LoFtool: 0.491
RVIS EVS: -0.46
RVIS percentile EVS: 23.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.884

Gene Damage Prediction

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