PTPN9

Chr 15

protein tyrosine phosphatase non-receptor type 9

Also known as: MEG2, PTPMEG2

NCBI Gene: 5780 ENSG00000169410 UniProt: P43378

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. This PTP contains an N-terminal domain that shares a significant similarity with yeast SEC14, which is a protein that has phosphatidylinositol transfer activity and is required for protein secretion through the Golgi complex in yeast. This PTP was found to be activated by polyphosphoinositide, and is thought to be involved in signaling events regulating phagocytosis. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.110

Z-score 3.85

OE 0.26 (0.15–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.10Z-score

OE missense 0.67 (0.60–0.75)

223 obs / 330.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.15–0.46)

0≤0.351.4

Missense OE?0.67 (0.60–0.75)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 8 / 31.2Missense obs/exp: 223 / 330.5Syn Z: 1.07

Background carrier burden — how many people carry a rare variant somewhere in PTPN9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

628 rare PASS variants

Rare truncating (LoF)

1 in 2,400

82 rare PASS variants

Rare synonymous (reference)

1 in 240

302 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PTPN9. 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 140	1 in 3,000
South Asian	~43k	1 in 92	1 in 3,100
Remaining (unassigned)	~30k	1 in 82	1 in 3,400
European (Finnish)	~27k	1 in 380	1 in 4,400
Admixed American	~22k	1 in 120	1 in 1,500
African / African American	~21k	1 in 110	1 in 1,000
East Asian	~20k	1 in 110	1 in 2,900
Ashkenazi Jewish	~13k	1 in 670	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 180	none seen

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 13.? see exons ↓