PDGFRB

Chr 5

platelet derived growth factor receptor beta

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

NCBI Gene: 5159ENSG00000113721UniProt: P09619

The protein encoded by this gene is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer (PDGFB or PDGFD) or a heterodimer (PDGFA and PDGFB). This gene is essential for normal development of the cardiovascular system and aids in rearrangement of the actin cytoskeleton. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the ETV6 gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Aug 2017]

GeneReviewsResearchGenerating clinical summary…
GOFmechanismLOEUF 0.33
Clinical Summary— PDGFRB
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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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ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 318 VUS of 852 total submissions
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — PDGFRB
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
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.33LOEUF
pLI 0.904
Z-score 5.58
OE 0.20 (0.12–0.33)
Highly constrained

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

Missense Constraint?
1.84Z-score
OE missense 0.80 (0.75–0.86)
563 obs / 700.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.12–0.33)
0≤0.351.4
Missense OE?0.80 (0.75–0.86)
0≤0.61.4
Synonymous OE?1.08
0≤1.21.6
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

This gene — mechanism propensity

DN
0.5674th %ile
GOF
0.75top 25%
LOF
0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). 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 · 1 literature citation · 97% of P/LP are missense
LOF1 literature citation · LOEUF 0.33

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).1
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.2

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. 1.PMID 31710779 ↗
  2. 2.PMID 26599395 ↗

ClinVar Variant Classifications

852 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic9
VUS318
Likely Benign310
Benign120
Conflicting42
20
Pathogenic
9
Likely Pathogenic
318
VUS
310
Likely Benign
120
Benign
42
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
19
1
0
20
Likely Pathogenic
0
9
0
0
9
VUS
19
285
10
4
318
Likely Benign
0
73
95
142
310
Benign
0
14
73
33
120
Conflicting
—42
Total19400179179819

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap PDGFRB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PDGFRB · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients