SKAP2

protein-coding

src kinase associated phosphoprotein 2, the group of Pleckstrin homology domain containing

Gene summary

The protein encoded by this gene shares homology with Src kinase-associated phosphoprotein 1, and is a substrate of Src family kinases. It is an adaptor protein that is thought to play an essential role in the Src signaling pathway, and in regulating proper activation of the immune system. This protein contains an amino terminal coiled-coil domain for self-dimerization, a plecskstrin homology (PH) domain required for interactions with lipids at the membrane, and a Src homology (SH3) domain at the carboxy terminus. Some reports indicate that this protein inhibits actin polymerization through interactions with actin assembly factors, and might negatively regulate the invasiveness of tumors by modulating actin assembly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

Previous symbols:

SCAP2

MANE transcript

NM_003930.5

Inheritance

—

ClinVar variants

U:39B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr7:26,667,068-26,995,239

External References & Databases

Ensembl (ENSG00000005020)

Transcript & Mutation Effects

hg38 • Region Span ~328.2 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 SKAP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003930.5. 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			36 clinvar	2 clinvar	2 clinvar	40
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	39	2	3	44

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003930.5	RefSeq	NP_003921.2	12	MANE Select
ENST00000345317.7	Ensembl	ENSP00000005587.2	12	MANE Select
NM_001303468.2	RefSeq	NP_001290397.1	6	Standard
ENST00000432747.1	Ensembl	ENSP00000408163.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TCR
Signal regulatory protein family interactions
Cell-Cell communication

Biological Process

signal transduction
negative regulation of cell population proliferation
positive regulation of signal transduction
B cell activation
protein-containing complex assembly

Molecular Function

SH3/SH2 adaptor activity
protein binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000345317
Coding exons: 12
Length: 328178
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125747
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.30	133	182	0.730	0.00000857	2390
Missense (PolyPhen)		29	67.653	0.42866		912
Synonymous	-0.465	63	58.5	1.08	0.00000260	599
Loss of Function	2.76	9	23.4	0.384	0.00000106	305

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in B-cell and macrophage adhesion processes. In B-cells, may act by coupling the B-cell receptor (BCR) to integrin activation. May play a role in src signaling pathway. {ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:9837776}.;

Recessive Scores

pRec: 0.262

Intolerance Scores

LoFtool: 0.509
RVIS EVS: 0.17
RVIS percentile EVS: 65.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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