RASAL2

protein-coding

RAS protein activator like 2, the group of C2 and RasGAP domain containing|Pleckstrin homology domain containing

Gene summary

This gene encodes a protein that contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs function as activators of Ras superfamily of small GTPases. The protein encoded by this gene is able to complement the defective RasGAP function in a yeast system. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_170692.4

Inheritance

—

ClinVar variants

U:179B:9

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr1:178,094,104-178,484,147

External References & Databases

Ensembl (ENSG00000075391)

Transcript & Mutation Effects

hg38 • Region Span ~390.0 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 RASAL2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 171

not providedTotal: 7

AutismTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_170692.4. 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			2 clinvar	4 clinvar	2 clinvar	8
missense			173 clinvar	3 clinvar		176
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	179	7	2	188

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_170692.4	RefSeq	NP_733793.2	18	MANE Select
ENST00000367649.8	Ensembl	ENSP00000356621.3	18	MANE Select
NM_001437625.1	RefSeq	NP_001424554.1	19	Standard
NM_001437626.1	RefSeq	NP_001424555.1	18	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
signal transduction
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367649
Coding exons: 18
Length: 385781
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.40	615	721	0.853	0.0000402	8420
Missense (PolyPhen)		275	344.71	0.79776		4028
Synonymous	0.508	253	263	0.960	0.0000133	2496
Loss of Function	5.61	12	58.1	0.207	0.00000310	677

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.241
RVIS EVS: -2.1
RVIS percentile EVS: 1.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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