SIRPA

protein-coding

signal regulatory protein alpha, the group of Signal regulatory proteins|V-set domain containing|CD molecules|Ig-like cell adhesion molecule family|C1-set domain containing

Gene summary

The protein encoded by this gene is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. This protein can be phosphorylated by tyrosine kinases. The phospho-tyrosine residues of this PTP have been shown to recruit SH2 domain containing tyrosine phosphatases (PTP), and serve as substrates of PTPs. This protein was found to participate in signal transduction mediated by various growth factor receptors. CD47 has been demonstrated to be a ligand for this receptor protein. This gene and its product share very high similarity with several other members of the SIRP family. These related genes are located in close proximity to each other on chromosome 20p13. Multiple alternatively spliced transcript variants have been determined for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

PTPNS1

MANE transcript

NM_001040023.2

Inheritance

—

ClinVar variants

U:75B:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr20:1,894,167-1,940,592

External References & Databases

Ensembl (ENSG00000198053)

Transcript & Mutation Effects

hg38 • Region Span ~46.4 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 SIRPA variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040023.2. 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			3 clinvar	3 clinvar	2 clinvar	8
missense			68 clinvar	10 clinvar	2 clinvar	80
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	75	13	4	92

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 95 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040023.2	RefSeq	NP_001035112.1	8	MANE Select
ENST00000358771.5	Ensembl	ENSP00000351621.4	8	MANE Select
NM_001040022.1	RefSeq	NP_001035111.1	8	Standard
NM_001330728.1	RefSeq	NP_001317657.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Osteoclast differentiation - Homo sapiens (human)
EGF-Ncore
Prolactin Signaling Pathway
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
Cardiac Progenitor Differentiation

Biological Process

negative regulation of protein phosphorylation
cell adhesion
regulation of gene expression
cell migration
positive regulation of cell-cell adhesion

Molecular Function

SH3 domain binding
protein phosphatase binding
GTPase regulator activity
protein binding involved in heterotypic cell-cell adhesion
cell-cell adhesion mediator activity

Cellular Component

plasma membrane
integral component of plasma membrane
cell surface
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358771
Coding exons: 8
Length: 45390
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.06	243	294	0.826	0.0000180	3193
Missense (PolyPhen)		75	103.44	0.72503		1261
Synonymous	-0.867	145	132	1.10	0.00000941	1033
Loss of Function	3.45	4	21.1	0.190	0.00000107	243

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. {ECO:0000250, ECO:0000269|PubMed:10469599, ECO:0000269|PubMed:11509594}.;

Intolerance Scores

LoFtool: 0.452
RVIS EVS: -0.78
RVIS percentile EVS: 13.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.951

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High