PLGRKT

Chr 9

plasminogen receptor with a C-terminal lysine

Also known as: AD025, C9orf46, MDS030, PLG-RKT, Plg-R(KT)

The PLGRKT protein serves as a receptor for plasminogen and regulates cell surface plasminogen activation, including involvement in neuroendocrine prohormone processing and inflammatory response regulation. Mutations in PLGRKT cause autosomal recessive plasminogen receptor deficiency, which presents with developmental delays, intellectual disability, and seizures typically manifesting in early childhood. The condition primarily affects the nervous system with additional features that may include growth abnormalities and metabolic dysfunction.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.87
Clinical SummaryPLGRKT
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.87LOEUF
pLI 0.000
Z-score -0.72
OE 1.28 (0.781.87)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.09Z-score
OE missense 1.35 (1.151.59)
104 obs / 77.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.28 (0.781.87)
00.351.4
Missense OE1.35 (1.151.59)
00.61.4
Synonymous OE1.48
01.21.6
LoF obs/exp: 10 / 7.8Missense obs/exp: 104 / 77.0Syn Z: -1.89
DN
0.75top 25%
GOF
0.78top 25%
LOF
0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PLGRKT · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC