PKD2

Chr 4AD

polycystin 2, transient receptor potential cation channel

Also known as: APKD2, PC2, PKD4, Pc-2, TRPP2

NCBI Gene: 5311 ENSG00000118762 UniProt: Q13563 OMIM: 173910

The protein encoded by this gene functions as a calcium-permeable cation channel in renal epithelial cells and primary cilia, where it is involved in fluid-flow mechanosensation and calcium signaling. Mutations cause autosomal dominant polycystic kidney disease type 2, which primarily affects the kidneys through progressive cyst formation. This gene is highly constrained against loss-of-function variants (LOEUF 0.497), indicating that complete loss of protein function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

MultiplemechanismADLOEUF 0.502 OMIM phenotypes

Clinical Summary— PKD2

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Gene-Disease Validity (ClinGen)

autosomal dominant polycystic kidney disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

107 unique Pathogenic / Likely Pathogenic· 203 VUS of 400 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PKD2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint

0.50LOEUF

pLI 0.000

Z-score 4.36

OE 0.33 (0.22–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint

0.27Z-score

OE missense 0.96 (0.89–1.04)

449 obs / 465.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.33 (0.22–0.50)

0≤0.351.4

Missense OE0.96 (0.89–1.04)

0≤0.61.4

Synonymous OE1.18

0≤1.21.6

LoF obs/exp: 16 / 48.9Missense obs/exp: 449 / 465.5Syn Z: -1.91

0.76top 25%

GOF

0.84top 5%

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, loss-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 · 1 literature citation

LOF1 literature citation · 93% of P/LP variants are LoF · LOEUF 0.50

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.

Literature Evidence

GOFAutosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 gene, encoding the polycystic kidney disease protein polycystin-1 and the transient receptor potential channel polycystin-2 (also known as TRPP2), respectively.PMID:31441214

LOFA loss-of-function model for cystogenesis in human autosomal dominant polycystic kidney disease type 2.PMID:10417277

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

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70

Likely Pathogenic37

VUS203

Likely Benign75

Benign2

Conflicting2

Pathogenic

Likely Pathogenic

203

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	68	0	2	0	70
Likely Pathogenic	32	3	1	1	37
VUS	1	180	18	4	203
Likely Benign	0	3	19	53	75
Benign	0	1	1	0	2
Conflicting	—				2
Total	101	187	41	58	389

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

View in ClinVar →

Protein Context — Lollipop Plot

PKD2 · 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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — PKD2

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

RADIOLOGICAL AND CLINICAL EVALUATION OF RENAL EMBOLIZATION USING EVOH IN DIALYSIS PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A PROSPECTIVE LONGITUDINAL OBSERVATIONAL STUDY

RECRUITING

NCT07535385Fondazione IRCCS Policlinico San Matteo di PaviaStarted 2020-08-17

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.

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3