PTPN2

Chr 18

protein tyrosine phosphatase non-receptor type 2

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

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.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
48
Pubs (1 yr)
89
P/LP submissions
0%
P/LP missense
0.18
LOEUF· LoF intol.
Mechanism
Clinical SummaryPTPN2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
85 unique Pathogenic / Likely Pathogenic· 45 VUS of 161 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 4.59
OE 0.04 (0.010.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.38Z-score
OE missense 0.74 (0.650.84)
163 obs / 220.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.04 (0.010.18)
00.351.4
Missense OE0.74 (0.650.84)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 1 / 26.4Missense obs/exp: 163 / 220.6Syn Z: 0.63

ClinVar Variant Classifications

161 submitted variants in ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic2
VUS45
Likely Benign5
Benign3
Conflicting1
83
Pathogenic
2
Likely Pathogenic
45
VUS
5
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
2
0
2
VUS
0
36
9
0
45
Likely Benign
0
1
0
4
5
Benign
0
2
1
0
3
Conflicting
1
Total039954139

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PTPN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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