PF4V1

Chr 4

platelet factor 4 variant 1

Also known as: CXCL4L1, CXCL4V1, PF4-ALT, PF4A, SCYB4V1

NCBI Gene: 5197 ENSG00000109272 UniProt: P10720 OMIM: 173461

The protein is a chemokine that inhibits angiogenesis and endothelial cell chemotaxis. Mutations cause autosomal recessive primary familial brain calcification, a neurodegenerative disorder characterized by bilateral calcification of the basal ganglia and other brain regions. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a chemokine that is highly similar to platelet factor 4. The encoded protein displays a strong antiangiogenic function and is regulated by chemokine (C-X-C motif) receptor 3. This protein also impairs tumor growth and can protect against blood-retinal barrier breakdown in diabetes patients. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.91

Clinical Summary— PF4V1

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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

25 VUS of 26 total submissions

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?

1.91LOEUF

pLI 0.001

Z-score -0.53

OE 1.33 (0.59–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.05Z-score

OE missense 0.98 (0.80–1.22)

60 obs / 61.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.33 (0.59–1.91)

0≤0.351.4

Missense OE?0.98 (0.80–1.22)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 4 / 3.0Missense obs/exp: 60 / 61.1Syn Z: -0.70

This gene — mechanism propensity

0.74top 25%

GOF

0.5660th %ile

LOF

0.1796th %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

26 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	25	25
Likely Benign	1	1
Benign	0	0
Total	26	26

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 PF4V1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →