PTPN6

Chr 12

protein tyrosine phosphatase non-receptor type 6

Also known as: HCP, HCPH, HPTP1C, PTP-1C, SH-PTP1, SHP-1, SHP-1L, SHP1

NCBI Gene: 5777ENSG00000111679UniProt: P29350

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

Research Assistant →
0
Active trials
40
Pubs (1 yr)
46
P/LP submissions
0%
P/LP missense
0.13
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— PTPN6
⚡
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.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 73 VUS of 168 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 5.39
OE 0.03 (0.01–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.87Z-score
OE missense 0.58 (0.52–0.65)
216 obs / 371.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.03 (0.01–0.13)
0≤0.351.4
Missense OE0.58 (0.52–0.65)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 1 / 35.8Missense obs/exp: 216 / 371.4Syn Z: 0.39

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic2
VUS73
Likely Benign9
Benign11
Conflicting1
43
Pathogenic
2
Likely Pathogenic
73
VUS
9
Likely Benign
11
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
2
0
2
VUS
1
58
14
0
73
Likely Benign
0
6
1
2
9
Benign
0
1
4
6
11
Conflicting
—1
Total165648139

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

View in ClinVar →

Protein Context — Lollipop Plot

PTPN6 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients