PDGFRB

Chr 5AD

platelet derived growth factor receptor beta

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

NCBI Gene: 5159 ENSG00000113721 UniProt: 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]

Primary Disease Associations & Inheritance

?Ocular pterygium-digital keloid dysplasia syndromeMIM #621091

Basal ganglia calcification, idiopathic, 4MIM #615007

Kosaki overgrowth syndromeMIM #616592

Myofibromatosis, infantile, 1MIM #228550

Premature aging syndrome, Penttinen typeMIM #601812

UniProtMyeloproliferative disorder chronic with eosinophilia

UniProtLeukemia, acute myelogenous

UniProtLeukemia, juvenile myelomonocytic

262

ClinVar variants

Pathogenic / LP

0.90

pLI score· haploinsufficient

Active trials

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

24 Pathogenic / Likely Pathogenic· 78 VUS of 262 total submissions

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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

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.84Z-score

OE missense 0.80 (0.75–0.86)

563 obs / 700.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.12–0.33)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08

0≤1.21.6

LoF obs/exp: 11 / 56.1Missense obs/exp: 563 / 700.1Syn Z: -1.09

ClinVar Variant Classifications

262 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic4

VUS78

Likely Benign104

Benign33

Conflicting23

Pathogenic

Likely Pathogenic

VUS

104

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	8	12	0	20
Likely Pathogenic	0	4	0	0	4
VUS	5	65	7	1	78
Likely Benign	0	32	33	39	104
Benign	0	8	8	17	33
Conflicting	—				23
Total	5	117	60	57	262

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

View 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.

Gene2Phenotype Curations

PDGFRB-related premature aging syndrome, Penttinen type

definitive

ADGain Of FunctionAltered Gene Product Structure

Dev. DisordersSkinSkeletal

G2P ↗

PDGFRB-related familial infantile myofibromatosis

definitive

ADGain Of FunctionAltered Gene Product Structure

Dev. DisordersSkinCancer

G2P ↗

missense variant

PDGFRB-related Kosaki overgrowth syndrome

definitive

ADGain Of FunctionAltered Gene Product Structure

Dev. DisordersSkeletal

G2P ↗

PDGFRB-related hereditary progressive mucinous histiocytosis

limited

ADUndeterminedAltered Gene Product Structure

Skin

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

PLATELET-DERIVED GROWTH FACTOR RECEPTOR, BETA; PDGFRB

MIM #173410 · *

?Ocular pterygium-digital keloid dysplasia syndrome

MIM #621091