PLGRKT

Chr 9

plasminogen receptor with a C-terminal lysine

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

NCBI Gene: 55848 ENSG00000107020 UniProt: Q9HBL7 OMIM: 618444

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in positive regulation of plasminogen activation. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.87

Clinical Summary— PLGRKT

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

29 VUS of 38 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -0.72

OE 1.28 (0.78–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.09Z-score

OE missense 1.35 (1.15–1.59)

104 obs / 77.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.28 (0.78–1.87)

0≤0.351.4

Missense OE?1.35 (1.15–1.59)

0≤0.61.4

Synonymous OE?1.48

0≤1.21.6

LoF obs/exp: 10 / 7.8Missense obs/exp: 104 / 77.0Syn Z: -1.89

This gene — mechanism propensity

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

38 submitted variants in ClinVar

ClinVar

Classification Summary

VUS29

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	29	0	29
Likely Benign	1	1	2
Benign	0	0	0
Total	30	1	31

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

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164 pathogenic / likely-pathogenic (of 174) ClinVar copy-number / structural variants overlap PLGRKT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →