PTPN2

Chr 18

protein tyrosine phosphatase non-receptor type 2

Also known as: PTN2, PTPT, TC-PTP, TC45, TC48, TCELLPTP, TCPTP

NCBI Gene: 5771 ENSG00000175354 UniProt: P17706 OMIM: 176887

This protein is a non-receptor tyrosine phosphatase that dephosphorylates multiple receptor and non-receptor protein tyrosine kinases, negatively regulating signaling pathways involved in immune system development, inflammatory responses, cell proliferation, and glucose homeostasis. Mutations cause autosomal recessive early-onset inflammatory bowel disease and T-cell immunodeficiency, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.18), indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in PTPN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

481 rare PASS variants

Rare truncating (LoF)

1 in 750

82 rare PASS variants

Rare synonymous (reference)

1 in 220

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PTPN2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 2,000
South Asian	~43k	1 in 100	1 in 8,400
Remaining (unassigned)	~30k	1 in 110	1 in 2,600
European (Finnish)	~27k	1 in 450	1 in 3,700
Admixed American	~22k	1 in 91	1 in 3,700
African / African American	~21k	1 in 100	1 in 780
East Asian	~20k	1 in 89	1 in 610
Ashkenazi Jewish	~13k	1 in 590	1 in 1,800
Middle Eastern	~2,884	1 in 140	≈ 1 in 820

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 9 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 9.? see exons ↓