PDGFRB

Chr 5AD

platelet derived growth factor receptor beta

Also known as: CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD, PDGFR, PDGFR-1

The protein encoded by PDGFRB is a cell surface tyrosine kinase receptor for platelet-derived growth factors that is essential for normal cardiovascular development and promotes proliferation and migration of pericytes and smooth muscle cells. Mutations cause autosomal dominant conditions including Kosaki overgrowth syndrome, infantile myofibromatosis, basal ganglia calcification, and Penttinen-type premature aging syndrome. The gene is highly constrained against loss-of-function variants (pLI 0.90, LOEUF 0.325), reflecting its critical role in development and cellular signaling.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.335 OMIM phenotypes
Clinical SummaryPDGFRB
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.904
Z-score 5.58
OE 0.20 (0.120.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.84Z-score
OE missense 0.80 (0.750.86)
563 obs / 700.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.120.33)
00.351.4
Missense OE0.80 (0.750.86)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 11 / 56.1Missense obs/exp: 563 / 700.1Syn Z: -1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePDGFRB-related premature aging syndrome, Penttinen typeGOFAD
definitivePDGFRB-related familial infantile myofibromatosisGOFAD
definitivePDGFRB-related Kosaki overgrowth syndromeGOFAD
limitedPDGFRB-related hereditary progressive mucinous histiocytosisOTHERAD
DN
0.5674th %ile
GOF
0.75top 25%
LOF
0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · LOEUF 0.33
GOFprediction above median · 1 literature citation

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.

Literature Evidence

GOFSpecific classes of de novo heterozygous gain-of-function pathogenic variants of the PDGFRB (platelet-derived growth factor receptor-beta) cause a distinctive overgrowth syndrome, named the Kosaki overgrowth syndrome (KOGS) (OMIM #616592).PMID:31710779
LOFWhile our findings provide clear evidence that loss-of-function mutations in PDGFB or PDGFRB cause PFBC, they also demonstrate species differences in the threshold levels of PDGF-B/PDGF-Rβ signaling that protect against small-vessel calcification in the brain.PMID:26599395

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PDGFRB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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