PDGFRL

Chr 8

platelet derived growth factor receptor like

Also known as: PDGRL, PRLTS

NCBI Gene: 5157 ENSG00000104213 UniProt: Q15198 OMIM: 604584

The protein shares significant sequence similarity with the ligand binding domain of platelet-derived growth factor receptor beta and functions as a tumor suppressor. Mutations cause somatic colorectal cancer and hepatocellular cancer, indicating these are acquired rather than inherited cancers. This gene is highly intolerant to loss-of-function variants in the general population, consistent with its tumor suppressor role.

OMIM ResearchSummary from RefSeq, OMIM

This gene encodes a protein with significant sequence similarity to the ligand binding domain of platelet-derived growth factor receptor beta. Mutations in this gene, or deletion of a chromosomal segment containing this gene, are associated with sporadic hepatocellular carcinomas, colorectal cancers, and non-small cell lung cancers. This suggests this gene product may function as a tumor suppressor. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Colorectal cancer, somaticMIM #114500

Hepatocellular cancer, somaticMIM #114550

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Colorectal cancer, somatic; Hepatocellular cancer, somatic; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.79

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.79LOEUF

pLI 0.000

Z-score -0.96

OE 1.27 (0.88–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.00Z-score

OE missense 1.38 (1.26–1.52)

303 obs / 219.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.27 (0.88–1.79)

0≤0.351.4

Missense OE?1.38 (1.26–1.52)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 19 / 15.0Missense obs/exp: 303 / 219.6Syn Z: -2.62

Background carrier burden — how many people carry a rare variant somewhere in PDGFRL?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

736 rare PASS variants

Rare truncating (LoF)

1 in 560

102 rare PASS variants

Rare synonymous (reference)

1 in 99

263 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDGFRL. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 570
South Asian	~43k	1 in 72	1 in 850
Remaining (unassigned)	~30k	1 in 55	1 in 420
European (Finnish)	~27k	1 in 160	1 in 3,300
Admixed American	~22k	1 in 62	1 in 1,200
African / African American	~21k	1 in 65	1 in 690
East Asian	~20k	1 in 61	1 in 440
Ashkenazi Jewish	~13k	1 in 340	none seen
Middle Eastern	~2,884	1 in 67	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 6.? see exons ↓