PF4

Chr 4

platelet factor 4

Also known as: CXCL4, PF-4, SCYB4

NCBI Gene: 5196 ENSG00000163737 UniProt: P02776 OMIM: 173460

The protein functions as a CXC chemokine released from activated platelets that regulates platelet aggregation, hematopoiesis, immune cell migration, and has anticoagulant effects through heparin binding. Mutations cause autosomal dominant thrombocytopenia-5, a bleeding disorder characterized by reduced platelet counts and abnormal platelet function. The gene shows low constraint to loss-of-function variation, suggesting that complete loss of protein function may be tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the CXC chemokine family. This chemokine is released from the alpha granules of activated platelets in the form of a homotetramer which has high affinity for heparin and is involved in platelet aggregation. This protein is chemotactic for numerous other cell type and also functions as an inhibitor of hematopoiesis, angiogenesis and T-cell function. The protein also exhibits antimicrobial activity against Plasmodium falciparum. [provided by RefSeq, Oct 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.73

Clinical Summary— PF4

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

14 VUS of 15 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.043

Z-score 0.53

OE 0.67 (0.27–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.26Z-score

OE missense 0.90 (0.72–1.14)

51 obs / 56.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.27–1.73)

0≤0.351.4

Missense OE?0.90 (0.72–1.14)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 2 / 3.0Missense obs/exp: 51 / 56.5Syn Z: 0.18

This gene — mechanism propensity

0.78top 25%

GOF

0.5660th %ile

LOF

0.1697th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

15 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

Benign1

VUS

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	14	0	14
Likely Benign	0	0	0
Benign	0	1	1
Total	14	1	15

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap PF4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →