PTPRC

protein tyrosine phosphatase receptor type C, the group of Fibronectin type III domain containing|Protein tyrosine phosphatases receptor type|CD molecules

Basic information

Region (hg38): 1:198638457-198759342

Previous symbols: [ "CD45" ]

Links

ENSG00000081237 ∙ NCBI:5788 ∙ OMIM:151460 ∙ HGNC:9666 ∙ Uniprot:P08575 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 104 (Moderate), mode of inheritance: AR
• immunodeficiency 104 (Strong), mode of inheritance: AR
• T-B+ severe combined immunodeficiency due to CD45 deficiency (Supportive), mode of inheritance: AR
• immunodeficiency 104 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 105	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been described	Allergy/Immunology/Infectious	9068311; 11145714; 22689986

ClinVar

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

• Immunodeficiency 104 (13 variants)
• Immunodeficiency 105 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPRC 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			1	320	9	330
missense		1	307	9	3	320
nonsense	6					6
start loss			1			1
frameshift	7	1				8
inframe indel			4			4
splice donor/acceptor (+/-2bp)		14	1			15
splice region			14	63	5	82
non coding				260	49	309
Total	13	16	314	589	61

Highest pathogenic variant AF is 0.00000657

Variants in PTPRC

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

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

Position	Type	Phenotype	Significance	ClinVar
1-198638880-T-A			Likely benign (Oct 04, 2018)
1-198638984-C-T			Likely benign (Aug 06, 2019)
1-198639271-G-T		Immunodeficiency 104 • not specified	Uncertain significance (Jan 11, 2024)
1-198639274-C-T		Immunodeficiency 104	Likely benign (Sep 26, 2023)
1-198639277-G-C		Immunodeficiency 104	Uncertain significance (Oct 12, 2021)
1-198639284-T-A		Immunodeficiency 104	Uncertain significance (Sep 01, 2021)
1-198639292-A-G		Immunodeficiency 104	Likely benign (Oct 13, 2023)
1-198639307-C-T		Immunodeficiency 104	Benign (Jan 29, 2024)
1-198639320-G-A		Immunodeficiency 104	Uncertain significance (Dec 15, 2019)
1-198639325-A-C		Immunodeficiency 104	Likely benign (Jan 17, 2024)
1-198639342-G-A		Immunodeficiency 104	Likely pathogenic (Oct 06, 2023)
1-198639349-C-T		Immunodeficiency 104	Likely benign (Jun 07, 2023)
1-198639350-A-G		Immunodeficiency 104	Likely benign (Mar 03, 2023)
1-198639352-G-A		Immunodeficiency 104	Likely benign (Nov 27, 2023)
1-198639354-A-T		Immunodeficiency 104	Likely benign (Jan 31, 2024)
1-198639359-A-G		Immunodeficiency 104	Likely benign (Mar 18, 2023)
1-198639360-A-G		Immunodeficiency 104	Likely benign (Dec 30, 2023)
1-198692077-T-G			Benign (Apr 26, 2020)
1-198692372-TG-T		Severe combined immunodeficiency disease	Likely pathogenic (Mar 29, 2022)
1-198693776-A-G			Benign (Aug 19, 2018)
1-198694217-G-A			Benign (Aug 06, 2019)
1-198694393-C-T			Likely benign (Dec 05, 2018)
1-198696518-T-C			Likely benign (Dec 05, 2018)
1-198696570-A-G			Benign (Aug 19, 2018)
1-198696692-C-T		Immunodeficiency 104	Likely benign (Dec 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTPRC	protein_coding	protein_coding	ENST00000442510	32	118745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000431	125705	1	42	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.17	597	683	0.874	0.0000341	8660
Missense in Polyphen		171	236.39	0.72339		3048
Synonymous	-0.902	259	241	1.07	0.0000126	2374
Loss of Function	6.86	8	69.9	0.115	0.00000346	881

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000299	0.000298
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000490	0.000489
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000108	0.000105
Middle Eastern	0.000490	0.000489
South Asian	0.000327	0.000294
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:11909961, ECO:0000269|PubMed:2845400}.
• Disease: DISEASE: Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:608971]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. {ECO:0000269|PubMed:11145714}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple sclerosis (MS) [MIM:126200]: A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. {ECO:0000269|PubMed:11101853}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• Pathway: Primary immunodeficiency - Homo sapiens (human);Cell adhesion molecules (CAMs) - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);JAK-STAT-Ncore;B Cell Receptor Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;EPO Receptor Signaling;Interferon type I signaling pathways;Developmental Biology;Neutrophil degranulation;lck and fyn tyrosine kinases in initiation of tcr activation;role of mef2d in t-cell apoptosis;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;t cell receptor signaling pathway;Phosphorylation of CD3 and TCR zeta chains;TCR signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;CXCR4-mediated signaling events;BCR signaling pathway;Other semaphorin interactions;Semaphorin interactions;IL3;Axon guidance;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.670

Intolerance Scores

• rvis_EVS: 0.23
• rvis_percentile_EVS: 68.57

Haploinsufficiency Scores

• pHI: 0.177
• hipred: N
• hipred_score: 0.266
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptprc
• Phenotype: liver/biliary system phenotype; respiratory system phenotype; neoplasm; hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary 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); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: activation of MAPK activity;natural killer cell differentiation;negative regulation of T cell mediated cytotoxicity;positive regulation of T cell mediated cytotoxicity;negative regulation of cytokine-mediated signaling pathway;hematopoietic progenitor cell differentiation;immunoglobulin biosynthetic process;positive regulation of humoral immune response mediated by circulating immunoglobulin;negative regulation of protein kinase activity;protein dephosphorylation;negative regulation of cell adhesion involved in substrate-bound cell migration;leukocyte cell-cell adhesion;cell surface receptor signaling pathway;response to gamma radiation;regulation of gene expression;dephosphorylation;B cell differentiation;T cell differentiation;positive regulation of B cell proliferation;cellular response to extracellular stimulus;negative regulation of protein autophosphorylation;regulation of interleukin-8 production;positive regulation of tumor necrosis factor production;heterotypic cell-cell adhesion;peptidyl-tyrosine dephosphorylation;calcium-mediated signaling using intracellular calcium source;T cell proliferation;B cell proliferation;positive regulation of T cell proliferation;T cell activation;neutrophil degranulation;positive regulation of MAPK cascade;cell cycle phase transition;plasma membrane raft distribution;positive thymic T cell selection;negative thymic T cell selection;negative regulation of interleukin-2 biosynthetic process;positive regulation of interleukin-2 biosynthetic process;regulation of B cell differentiation;positive regulation of gamma-delta T cell differentiation;positive regulation of protein kinase activity;regulation of JAK-STAT cascade;positive regulation of alpha-beta T cell proliferation;positive regulation of isotype switching to IgG isotypes;bone marrow development;stem cell development;positive regulation of peptidyl-tyrosine phosphorylation;regulation of phagocytosis;T cell receptor signaling pathway;B cell receptor signaling pathway;regulation of B cell receptor signaling pathway;positive regulation of antigen receptor-mediated signaling pathway;release of sequestered calcium ion into cytosol;defense response to virus;regulation of cell cycle;regulation of protein tyrosine kinase activity;negative regulation of protein tyrosine kinase activity;negative regulation of ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;positive regulation of protein tyrosine phosphatase activity;negative regulation of microglial cell activation;DN2 thymocyte differentiation;positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of hematopoietic stem cell migration;positive regulation of stem cell proliferation;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;focal adhesion;external side of plasma membrane;cytoplasmic side of plasma membrane;cell surface;membrane;integral component of membrane;secretory granule membrane;bleb;membrane raft;extracellular exosome;membrane microdomain
• Molecular function: protein tyrosine phosphatase activity;transmembrane receptor protein tyrosine phosphatase activity;signaling receptor binding;protein binding;heparin binding;protein kinase binding;ankyrin binding;spectrin binding;protein homodimerization activity;heparan sulfate proteoglycan binding