SLA2

protein-coding

Src like adaptor 2, the group of SH2 domain containing

Gene summary

This gene encodes a member of the SLAP family of adapter proteins. The encoded protein may play an important receptor-proximal role in downregulating T and B cell-mediated responses and inhibits antigen receptor-induced calcium mobilization. This protein interacts with Cas-Br-M (murine) ecotropic retroviral transforming sequence c. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

C20orf156

MANE transcript

NM_032214.4

Inheritance

—

ClinVar variants

U:41B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr20:36,612,318-36,646,196

External References & Databases

Ensembl (ENSG00000101082)

Transcript & Mutation Effects

hg38 • Region Span ~33.9 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 SLA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032214.4. 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		2
missense			39 clinvar	1 clinvar	2 clinvar	42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	41	3	2	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032214.4	RefSeq	NP_115590.1	7	MANE Select
ENST00000262866.9	Ensembl	ENSP00000262866.4	7	MANE Select
NM_175077.3	RefSeq	NP_778252.1	7	Standard
ENST00000360672.2	Ensembl	ENSP00000353890.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TCR
BCR
TCR signaling in na&#xef
ve CD4+ T cells

Biological Process

negative regulation of transcription by RNA polymerase II
positive regulation of signal transduction
B cell mediated immunity
intracellular receptor signaling pathway
T cell activation

Molecular Function

SH3/SH2 adaptor activity
protein binding
1-phosphatidylinositol-3-kinase regulator activity
protein N-terminus binding

Cellular Component

nucleoplasm
cytoplasm
late endosome
Golgi apparatus
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262866
Coding exons: 7
Length: 33899
Individuals with no LoFs: 125726
Homozygous LoFs: 1
Heterozygous LoFs: 20
Defined: 125747
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.102	147	151	0.977	0.00000847	1663
Missense (PolyPhen)		47	59.724	0.78696		628
Synonymous	-0.0930	68	67.0	1.01	0.00000407	555
Loss of Function	2.24	4	12.6	0.319	5.30e-7	154

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.00013	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins. {ECO:0000269|PubMed:11696592}.;

Recessive Scores

pRec: 0.234

Intolerance Scores

LoFtool: 0.260
RVIS EVS: 0.26
RVIS percentile EVS: 70.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.685

Gene Damage Prediction

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