SIRPA

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

Basic information

Region (hg38): 20:1894167-1940592

Previous symbols: [ "PTPNS1" ]

Links

ENSG00000198053 ∙ NCBI:140885 ∙ OMIM:602461 ∙ HGNC:9662 ∙ Uniprot:P78324 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIRPA gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIRPA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	2	5
missense			29	5	2	36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	29	8	4

Variants in SIRPA

This is a list of pathogenic ClinVar variants found in the SIRPA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-1915239-C-T		not specified	Uncertain significance (Dec 20, 2023)
20-1915360-C-G		not specified	Uncertain significance (Sep 30, 2024)
20-1915372-C-T			Likely benign (Nov 01, 2022)
20-1921428-C-T		not specified	Uncertain significance (Sep 17, 2021)
20-1921445-C-G		not specified	Likely benign (Jun 22, 2023)
20-1921454-G-C		not specified	Uncertain significance (Aug 28, 2023)
20-1921469-G-A		not specified	Likely benign (Jul 05, 2023)
20-1921545-C-G		not specified	Uncertain significance (Jul 09, 2021)
20-1921556-C-T		not specified	Uncertain significance (Aug 14, 2024)
20-1921559-G-A			Benign (Jul 23, 2018)
20-1921571-G-A		not specified	Uncertain significance (May 17, 2023)
20-1921595-G-A			Benign (Nov 15, 2017)
20-1921613-C-T		not specified	Uncertain significance (Oct 08, 2024)
20-1921614-G-A		not specified	Uncertain significance (Sep 04, 2024)
20-1921616-G-A		not specified	Uncertain significance (May 17, 2023)
20-1921622-G-A		not specified	Uncertain significance (Jun 22, 2024)
20-1921622-G-C		not specified	Uncertain significance (Dec 06, 2022)
20-1921673-C-T		not specified	Uncertain significance (Sep 03, 2024)
20-1921706-A-G		not specified	Uncertain significance (Jan 24, 2023)
20-1921710-G-A		not specified	Uncertain significance (Nov 21, 2024)
20-1921718-A-G			Benign (Dec 31, 2019)
20-1922357-A-G		not specified	Uncertain significance (Jul 25, 2023)
20-1922363-G-T		not specified	Uncertain significance (Nov 13, 2023)
20-1922400-A-G		not specified	Uncertain significance (Nov 29, 2024)
20-1922415-C-G		not specified	Uncertain significance (Jul 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIRPA	protein_coding	protein_coding	ENST00000358771	8	45390

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.672	0.328	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	243	294	0.826	0.0000180	3193
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000273	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Osteoclast differentiation - Homo sapiens (human);EGF-Ncore;Prolactin Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Cardiac Progenitor Differentiation;JAK-STAT;Neutrophil degranulation;Prolactin;Innate Immune System;Immune System;EGFR1;Cell surface interactions at the vascular wall;Hemostasis;Signal regulatory protein family interactions;Cell-Cell communication (Consensus)

Intolerance Scores

• loftool: 0.452
• rvis_EVS: -0.78
• rvis_percentile_EVS: 13.05

Haploinsufficiency Scores

• pHI: 0.160
• hipred: N
• hipred_score: 0.466
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.951

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sirpa
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of protein phosphorylation;cell adhesion;regulation of gene expression;cell migration;positive regulation of cell-cell adhesion;regulation of interferon-gamma production;regulation of interleukin-1 beta production;regulation of interleukin-6 production;regulation of tumor necrosis factor production;negative regulation of interferon-beta production;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;heterotypic cell-cell adhesion;monocyte extravasation;neutrophil degranulation;negative regulation of nitric oxide biosynthetic process;regulation of nitric oxide biosynthetic process;negative regulation of JNK cascade;negative regulation of inflammatory response;negative regulation of phagocytosis;positive regulation of phagocytosis;regulation of catalytic activity;positive regulation of T cell activation;leukocyte migration;cellular response to hydrogen peroxide;negative regulation of ERK1 and ERK2 cascade;cellular response to lipopolysaccharide;cellular response to interferon-gamma;cellular response to interleukin-1;cellular response to interleukin-12;negative regulation of macrophage inflammatory protein 1 alpha production;negative regulation of chemokine (C-C motif) ligand 5 production;negative regulation of cytokine production involved in inflammatory response;negative regulation of I-kappaB phosphorylation
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;membrane;extracellular exosome;tertiary granule membrane;ficolin-1-rich granule membrane
• Molecular function: SH3 domain binding;protein phosphatase binding;GTPase regulator activity;protein binding involved in heterotypic cell-cell adhesion;cell-cell adhesion mediator activity;protein antigen binding;protein tyrosine kinase binding