PKD1

Chr 16AD

polycystin 1, transient receptor potential channel interacting

Also known as: PBP, PC1, Pc-1, TRPP1, eliosin

NCBI Gene: 5310ENSG00000008710UniProt: P98161

This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Polycystic kidney disease 1MIM #173900
AD
Polycystic kidney disease 1MIM #173900
AD
568
ClinVar variants
191
Pathogenic / LP
1.00
pLI score· haploinsufficient
5
Active trials
Clinical Summary— PKD1
🧬
Gene-Disease Validity (ClinGen)
autosomal recessive polycystic kidney disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
191 Pathogenic / Likely Pathogenic· 325 VUS of 568 total submissions
💊
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.
0.18LOEUF
pLI 1.000
Z-score 9.96
OE 0.12 (0.08–0.18)
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.
-4.32Z-score
OE missense 1.23 (1.20–1.27)
3329 obs / 2697.2 exp
Tolerant

Tolerant to missense variation

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.0.12 (0.08–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.23 (1.20–1.27)
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.1.63
0≤1.21.6
LoF obs/exp: 18 / 149.4Missense obs/exp: 3329 / 2697.2Syn Z: -17.86

ClinVar Variant Classifications

568 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic141
Likely Pathogenic50
VUS325
Likely Benign48
Benign2
Conflicting2
141
Pathogenic
50
Likely Pathogenic
325
VUS
48
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
101
4
36
0
141
Likely Pathogenic
28
11
11
0
50
VUS
1
292
30
2
325
Likely Benign
0
7
11
30
48
Benign
0
0
0
2
2
Conflicting
—2
Total1303148834568

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

View 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.

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM
POLYCYSTIN 1; PKD1
MIM #601313 · *

Polycystic kidney disease 1

MIM #173900

Molecular basis of disorder known

Autosomal dominant

Polycystic kidney disease 1

MIM #173900

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PKD1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Polycystic kidney disease.
Harris PC et al.·Annu Rev Med
2009Review
Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease.
Rossetti S et al.·J Am Soc Nephrol
2007
Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients.
Audrézet MP et al.·Hum Mutat
2012Cohort
Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing.
Rossetti S et al.·J Am Soc Nephrol
2012
Genetic Etiologies for Chronic Kidney Disease Revealed through Next-Generation Renal Gene Panel.
Bleyer AJ et al.·Am J Nephrol
2022
Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes.
Yang H et al.·Adv Kidney Dis Health
2023Review
Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).
Carrera P et al.·Sci Rep
2016Cohort
Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype.
Senum SR et al.·Am J Hum Genet
2022
Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank.
Jurgens SJ et al.·Nat Genet
2022
Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease.
Hwang YH et al.·J Am Soc Nephrol
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Polycystic Kidney Disease 1 (PKD1) Gene Variant Groups in Autosomal Dominant Polycystic Kidney Disease

ACTIVE NOT RECRUITING
NCT06747572Vertex Pharmaceuticals IncorporatedStarted 2024-12-19
Kidney Diseases

Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

NOT YET RECRUITING
NCT06291116Phase PHASE2University Hospital, RouenStarted 2026-03-01
standard care + rotigotine at 4 mg/24h for 24 months.standard care for 24 months.
Variant Nucleotide

Solving Challenging Diagnoses Through Ultra-long Read Sequencing

ACTIVE NOT RECRUITING
NCT06775613Phase NAIRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2023-03-10
Long-read sequencing
Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository

ENROLLING BY INVITATION
NCT03901521Weill Medical College of Cornell UniversityStarted 2018-06-01
Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Phase 2a Study of VX-407 in Participants With ADPKD Who Have a Subset of PKD1 Gene Variants (AGLOW)

RECRUITING
NCT07161037Phase PHASE2Vertex Pharmaceuticals IncorporatedStarted 2025-11-19
VX-407

External Resources

Links to major genomics databases and tools