PTPN14

Chr 1

protein tyrosine phosphatase non-receptor type 14

Also known as: CATLPH, PEZ, PTP36, PTPD2

NCBI Gene: 5784 ENSG00000152104 UniProt: Q15678

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 noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtChoanal atresia and lymphedema

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

LOF

Mechanism· G2P

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?

0.36LOEUF

pLI 0.221

Z-score 5.50

OE 0.23 (0.15–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.68Z-score

OE missense 0.82 (0.77–0.88)

591 obs / 717.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.15–0.36)

0≤0.351.4

Missense OE?0.82 (0.77–0.88)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 14 / 59.9Missense obs/exp: 591 / 717.6Syn Z: -0.39

Background carrier burden — how many people carry a rare variant somewhere in PTPN14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,346 rare PASS variants

Rare truncating (LoF)

1 in 2,400

117 rare PASS variants

Rare synonymous (reference)

1 in 54

659 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PTPN14. 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 49	1 in 2,600
South Asian	~43k	1 in 40	1 in 1,200
Remaining (unassigned)	~30k	1 in 35	1 in 5,000
European (Finnish)	~27k	1 in 92	1 in 2,000
Admixed American	~22k	1 in 38	1 in 2,500
African / African American	~21k	1 in 32	1 in 2,500
East Asian	~20k	1 in 42	1 in 1,700
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 44	≈ 1 in 2,800

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): 16 of 18 coding exons well covered in gnomAD exomes; exons 5, 11 marginal. Genomes: all 18.? see exons ↓