PDGFB

Chr 22

platelet derived growth factor subunit B

Also known as: IBGC5, PDGF-2, PDGF2, SIS, SSV, c-sis

NCBI Gene: 5155 ENSG00000100311 UniProt: P01127

The protein encodes platelet-derived growth factor subunit B, which regulates embryonic development, cell proliferation, and blood vessel development, particularly for recruiting pericytes and vascular smooth muscle cells in the central nervous system and other organs. Mutations cause autosomal dominant basal ganglia calcification (idiopathic basal ganglia calcification, type 5) and meningioma. The gene is highly constrained against loss-of-function variants, indicating that such variants are likely pathogenic when they occur.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

GeneReviews ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.46

Clinical Summary— PDGFB

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 85 VUS of 210 total submissions

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Clinical Trials

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

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PDGFB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.770

Z-score 2.92

OE 0.15 (0.06–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.08Z-score

OE missense 0.77 (0.66–0.89)

129 obs / 168.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.06–0.46)

0≤0.351.4

Missense OE?0.77 (0.66–0.89)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 2 / 13.6Missense obs/exp: 129 / 168.5Syn Z: -0.32

This gene — mechanism propensity

0.5476th %ile

GOF

0.2099th %ile

LOF

0.60top 25%

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

LOF56% of P/LP variants are LoF · LOEUF 0.46

DN1 literature citation

Literature Evidence

DNThe c.456+1G>C mutation in PDGFB resulted in aberrant mRNA splicing, thereby forming mature transcripts containing an in-frame 21 base pair (bp) deletion, which might create a stably truncated protein [p.(Val146_Gln152del)] and exert a dominant negative effect on wild-type PDGFB.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 34025715 ↗

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic10

VUS85

Likely Benign53

Benign37

Conflicting6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	4	1	0	15
Likely Pathogenic	4	4	2	0	10
VUS	5	75	4	1	85
Likely Benign	0	9	23	21	53
Benign	0	1	33	3	37
Conflicting	—				6
Total	19	93	63	25	206

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap PDGFB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →