PKD1L2

Chr 16

polycystin 1 like 2 (gene/pseudogene)

Also known as: PC1L2

NCBI Gene: 114780ENSG00000166473UniProt: Q7Z442OMIM: 607894

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.76
Clinical Summary— PKD1L2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 329 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE1.02 (0.57–1.76)
0≤0.351.4
Missense OE1.79 (1.61–1.96)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 7 / 6.9Missense obs/exp: 237 / 132.2Syn Z: -1.75
DN
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

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS329
Likely Benign29
4
Pathogenic
1
Likely Pathogenic
329
VUS
29
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
1
0
0
1
VUS
0
49
280
0
329
Likely Benign
0
4
25
0
29
Benign
0
0
0
0
0
Total0543090363

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

View in ClinVar →

Protein Context — Lollipop Plot

PKD1L2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis.
Diniz MG et al.·J Oral Pathol Med
2017
Systematic Review of Genetic Modifiers Associated with the Development and/or Progression of Nephropathy in Patients with Sickle Cell Disease.
Labarque V et al.·Int J Mol Sci
2024Review
Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.
Alzahrani OR et al.·Medicina (Kaunas)
2022
Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia.
Schaefer BA et al.·PLoS One
2016
A four-mRNA model to improve the prediction of breast cancer prognosis.
Qi L et al.·Gene
2019Functional
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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