PKD1L2

Chr 16

polycystin 1 like 2 (gene/pseudogene)

Also known as: PC1L2

NCBI Gene: 114780 ENSG00000166473 UniProt: Q7Z442

The protein encoded by this gene is a member of the polycystin family that may function as a G-protein-coupled receptor or regulator of cation channel pores, containing transmembrane domains and specialized protein domains. This gene appears to be extremely tolerant to loss-of-function variation in the general population (very low constraint scores), and it is noted to be a polymorphic pseudogene in humans. No established Mendelian diseases have been definitively linked to PKD1L2 mutations in pediatric populations.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the polycystin protein family. This protein may function as a G-protein-coupled component or regulator of cation channel pores. The long isoform of this protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene is a polymorphic pseudogene in humans. [provided by RefSeq, May 2022]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.76

Clinical Summary— PKD1L2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 469 VUS of 549 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.000

Z-score -0.04

OE 1.02 (0.57–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.24Z-score

OE missense 1.79 (1.61–1.96)

237 obs / 132.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.02 (0.57–1.76)

0≤0.351.4

Missense OE?1.79 (1.61–1.96)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 7 / 6.9Missense obs/exp: 237 / 132.2Syn Z: -1.75

This gene — mechanism propensity

0.6455th %ile

GOF

0.6930th %ile

LOF

0.2971th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). 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

DNprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

549 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS469

Likely Benign41

Benign1

Likely Pathogenic

469

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	1	193	275	0	469
Likely Benign	1	14	25	1	41
Benign	0	1	0	0	1
Total	2	209	300	1	512

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

View in ClinVar →

42 pathogenic / likely-pathogenic (of 88) ClinVar copy-number / structural variants overlap PKD1L2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →