PTPRC-gene

PTPRC is the acronym for "Protein Tyrosine Phosphatase Receptor Type C". The gene is
located on chromosome 1q31.3-q32.1 and encodes a protein known as leukocyte common antigen (LCA) or CD45. CD45 is an important leukocyte cell surface molecule with a high molecular weight. It belongs to the protein tyrosine phosphatase (PTP) family. PTPs are known signaling molecules that regulate a variety of cellular processes such as cell growth, differentiation, mitosis, and oncogenic transformation. CD45 is expressed on all hematopoietic cells except mature erythrocytes and their immediate progenitors. However, it is not found on other differentiated tissues; therefore, it can be used as an antigenic marker to identify undifferentiated hematopoietic tumors.

CD45 as a protein tyrosine phosphatase contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains and is therefore classified as a receptor-type PTP. CD45 is an essential regulator of T and B cell antigen receptor signaling. It functions either by direct interaction with components of the antigen receptor complexes or by activation of various Src family kinases required for antigen receptor signaling. PTPRC also represses JAK kinases and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcript variants of the PTPRC gene encoding different isoforms are known. Related signaling pathways include the Jak-Stat signaling path way and the B-cell receptor signaling pathway (KEGG). An important paralog of the gene is PTPRS.

Diseases associated with PTPRC include: "Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, Nk-cell positive" (SCID; 608971).

Tchilian et al (2001) concluded that CD45 screening should be performed in patients with otherwise unexplained immunodeficiency.

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T-CELL NEGATIVE, B-CELL POSITIVE, NK-CELL POSITIVE

In a child with T-, B+, NK+ SCID (608971), Kung et al (2000) found a compound heterozygosity at the PTPRC gene: the allele inherited from the mother carried a large deletion, while the other allele had a G-to-A transition at position +1 of the donor splice site of intron 13. Since the father did not carry the mutation, the allele was presumably spontaneously mutated (although paternity was not genetically established to protect family privacy).

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T-CELL NEGATIVE, B-CELL POSITIVE, NK-CELL POSITIVE.

In a Kurdish infant with T-, B+, NK+ SCID (608971), Tchilian et al (2001) identified a 6-bp deletion at nucleotide 1168 in exon 11 of the PTPRC gene that resulted in the deletion of 2 amino acids in the fibronectin type III module of the extracellular domain. The mutation resulted in a lack of surface PTPRC expression.

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T-CELL NEGATIVE, B-CELL POSITIVE, NK-CELL POSITIVE.

Roberts et al (2012) identified a boy with T-cell-negative, B-cell-positive, NK-cell-positive SCID (608971) born to parents not related by blood. The patient had no CD45 expression and was successfully treated with a maternal bone marrow transplant at 10 months of age. SNP array and whole-exon sequencing analysis revealed that the patient's mother was heterozygous for an A-to-T transversion at nucleotide 1618 of the CD45 gene. The paternal alleles had no detectable mutation. The defective chromosome also carried mutations in 7 other genes thought to have deleterious effects on protein function.

1. Akao Y et al (1987) Chromosomal assignments of genes coding for human leukocyte common antigen, T-200, and lymphocyte function-associated antigen 1, LFA-1 beta subunit. Somat Cell Molec Genet 13: 273-278.
2. Boxall S et al (2004) Disease associations and altered immune function in CD45 138G variant carriers. Hum Molec Genet 13: 2377-2384.
3. Cale CM et al (1997) Severe combined immunodeficiency with abnormalities in expression of the common leucocyte antigen, CD45. Arch. Dis. Child. 76: 163-164.
4. Kung C et al (2000) Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nature Med 6: 343-345
5. Roberts JL et al (2012) CD45-deficient severe combined immunodeficiency caused by uniparental disomy. Proc Nat Acad. Sci. 109: 10456-10461
6. Tchilian EZ et al (2001) A deletion in the gene encoding the CD45 antigen in a patient with SCID. J. Immun. 166: 1308-1313.