PLAT

Chr 8

plasminogen activator, tissue type

Also known as: T-PA, TPA

NCBI Gene: 5327 ENSG00000104368 UniProt: P00750 OMIM: 173370

This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · thrombophilia, familial, due to decreased release of tissue plasminogen activator · AD · ClinGen 2023

evidence questions this relationship

Active trials

102

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.20

OE 0.40 (0.26–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.42Z-score

OE missense 0.94 (0.86–1.03)

332 obs / 354.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.26–0.63)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 13 / 32.7Missense obs/exp: 332 / 354.3Syn Z: -0.12

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

729 rare PASS variants

Rare truncating (LoF)

1 in 520

123 rare PASS variants

Rare synonymous (reference)

1 in 100

334 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLAT. 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 130	1 in 1,200
South Asian	~43k	1 in 75	1 in 640
Remaining (unassigned)	~30k	1 in 77	1 in 1,400
European (Finnish)	~27k	1 in 190	1 in 2,900
Admixed American	~22k	1 in 58	1 in 2,800
African / African American	~21k	1 in 57	1 in 1,200
East Asian	~20k	1 in 82	1 in 2,500
Ashkenazi Jewish	~13k	1 in 420	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 58	1 in 480

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.