PKD1
Chr 16ADpolycystin 1, transient receptor potential channel interacting
Also known as: PBP, PC1, Pc-1, TRPP1, eliosin
The encoded protein forms a heteromeric calcium-permeable ion channel with PKD2 that regulates intracellular calcium homeostasis, controls cilium length in renal epithelium, and is involved in fluid-flow mechanosensation and renal tubulogenesis. Mutations cause autosomal dominant polycystic kidney disease type 1, characterized by progressive growth of fluid-filled cysts that replace normal renal tissue and lead to end-stage renal failure. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.179), indicating high biological constraint.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PKD1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Polycystic Kidney Disease 1 (PKD1) Gene Variant Groups in Autosomal Dominant Polycystic Kidney Disease
ACTIVE NOT RECRUITINGAutosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository
ENROLLING BY INVITATIONPhase 2a Study of VX-407 in Participants With ADPKD Who Have a Subset of PKD1 Gene Variants (AGLOW)
RECRUITINGSolving Challenging Diagnoses Through Ultra-long Read Sequencing
ACTIVE NOT RECRUITINGSafety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease
NOT YET RECRUITINGRADIOLOGICAL AND CLINICAL EVALUATION OF RENAL EMBOLIZATION USING EVOH IN DIALYSIS PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A PROSPECTIVE LONGITUDINAL OBSERVATIONAL STUDY
RECRUITINGExternal Resources
Links to major genomics databases and tools