PKD2
polycystin 2, transient receptor potential cation channel, the group of Transient receptor potential cation channels|EF-hand domain containing
Basic information
Region (hg38): 4:88007635-88077777
Links
Phenotypes
GenCC
Source:
- polycystic kidney disease 2 (Strong), mode of inheritance: AD
- polycystic kidney disease 2 (Strong), mode of inheritance: AD
- autosomal dominant polycystic kidney disease (Supportive), mode of inheritance: AD
- autosomal dominant polycystic kidney disease (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Polycystic kidney disease 2 with or without polycystic liver disease | AD | Cardiovascular; Gastrointestinal; Pharmacogenomic; Renal | A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial | Cardiovascular; Gastrointestinal; Renal | 8650545; 9402976; 9326320; 9773786; 9573526; 11156533; 11752048; 17699192; 17699202; 16707749; 17035604; 19443633; 20301424; 20219616; 21544064; 21551026 |
ClinVar
This is a list of variants' phenotypes submitted to
- Polycystic kidney disease 2 (89 variants)
- not provided (44 variants)
- Autosomal dominant polycystic kidney disease (43 variants)
- Polycystic kidney disease (21 variants)
- PKD2-related disorder (12 variants)
- Inborn genetic diseases (6 variants)
- not specified (3 variants)
- Autosomal recessive polycystic kidney disease (1 variants)
- Hypertensive disorder;Polycystic kidney disease;Chronic kidney disease (1 variants)
- Polycystic kidney disease;Multicystic kidney dysplasia;Polycystic liver disease 1 (1 variants)
- Elevated systolic blood pressure;Elevated diastolic blood pressure;Polycystic kidney disease (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKD2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 124 | 134 | ||||
| missense | 12 | 349 | 13 | 376 | ||
| nonsense | 52 | 60 | ||||
| start loss | 1 | |||||
| frameshift | 69 | 15 | 85 | |||
| inframe indel | 10 | 14 | ||||
| splice donor/acceptor (+/-2bp) | 19 | 16 | 39 | |||
| splice region | 2 | 18 | 16 | 36 | ||
| non coding | 33 | 61 | 32 | 126 | ||
| Total | 140 | 53 | 402 | 200 | 40 |
Highest pathogenic variant AF is 0.0000133
Variants in PKD2
This is a list of pathogenic ClinVar variants found in the PKD2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-88007652-G-A | Polycystic kidney disease 2 | Uncertain significance (Jan 12, 2018) | ||
| 4-88007652-G-C | Polycystic kidney disease 2 | Likely benign (Aug 23, 2019) | ||
| 4-88007666-A-G | Polycystic kidney disease 2 | Uncertain significance (Jan 13, 2018) | ||
| 4-88007670-C-T | Polycystic kidney disease 2 | Uncertain significance (Jan 13, 2018) | ||
| 4-88007687-G-C | Polycystic kidney disease 2 | Uncertain significance (Jan 12, 2018) | ||
| 4-88007708-C-T | Polycystic kidney disease 2 | Uncertain significance (Jan 13, 2018) | ||
| 4-88007720-C-A | Polycystic kidney disease | Likely benign (-) | ||
| 4-88007731-G-A | PKD2-related disorder | Likely benign (Jul 14, 2021) | ||
| 4-88007735-T-A | Autosomal dominant polycystic kidney disease | Uncertain significance (Feb 28, 2024) | ||
| 4-88007739-G-A | Autosomal dominant polycystic kidney disease | Likely benign (Jul 20, 2023) | ||
| 4-88007742-C-T | Polycystic kidney disease 2 • Autosomal dominant polycystic kidney disease • PKD2-related disorder | Conflicting classifications of pathogenicity (Oct 22, 2023) | ||
| 4-88007744-C-A | Uncertain significance (Feb 15, 2023) | |||
| 4-88007750-G-A | Autosomal dominant polycystic kidney disease | Uncertain significance (Jun 08, 2022) | ||
| 4-88007751-C-G | Autosomal dominant polycystic kidney disease | Likely benign (May 30, 2022) | ||
| 4-88007752-G-A | Autosomal dominant polycystic kidney disease • Inborn genetic diseases | Uncertain significance (May 23, 2023) | ||
| 4-88007756-A-G | Autosomal dominant polycystic kidney disease | Uncertain significance (Jun 04, 2022) | ||
| 4-88007768-C-T | Autosomal dominant polycystic kidney disease | Likely benign (Dec 06, 2023) | ||
| 4-88007770-G-C | Autosomal dominant polycystic kidney disease | Uncertain significance (Nov 21, 2023) | ||
| 4-88007772-G-C | Autosomal dominant polycystic kidney disease | Likely benign (Oct 24, 2021) | ||
| 4-88007773-GA-G | Polycystic kidney disease 2 • PKD2-related disorder | Conflicting classifications of pathogenicity (Jul 09, 2023) | ||
| 4-88007775-C-T | Autosomal dominant polycystic kidney disease | Likely benign (Feb 05, 2023) | ||
| 4-88007779-A-G | Autosomal dominant polycystic kidney disease • PKD2-related disorder | Uncertain significance (Aug 19, 2023) | ||
| 4-88007787-G-C | Autosomal dominant polycystic kidney disease | Likely benign (Nov 01, 2022) | ||
| 4-88007788-C-T | Autosomal dominant polycystic kidney disease | Uncertain significance (Mar 16, 2023) | ||
| 4-88007789-C-T | Autosomal dominant polycystic kidney disease | Uncertain significance (Jun 17, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PKD2 | protein_coding | protein_coding | ENST00000237596 | 15 | 70110 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000173 | 1.00 | 125716 | 0 | 29 | 125745 | 0.000115 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.272 | 449 | 466 | 0.964 | 0.0000268 | 6327 |
| Missense in Polyphen | 143 | 166.72 | 0.85775 | 2213 | ||
| Synonymous | -1.91 | 208 | 176 | 1.18 | 0.0000105 | 1891 |
| Loss of Function | 4.36 | 16 | 48.9 | 0.327 | 0.00000343 | 509 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000210 | 0.000210 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000218 | 0.000217 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.0000970 | 0.0000967 |
| Middle Eastern | 0.000218 | 0.000217 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Functions as a cation channel involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:18695040). Functions as outward-rectifying K(+) channel, but is also permeable to Ca(2+), and to a much lesser degree also to Na(+) (PubMed:11854751, PubMed:15692563, PubMed:27071085, PubMed:27991905). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (PubMed:11854751, PubMed:20881056). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). PKD1 and PKD2 may function through a common signaling pathway that is necessary to maintain the normal, differentiated state of renal tubule cells. Acts as a regulator of cilium length, together with PKD1. The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling. Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning. Detection of asymmetric nodal flow gives rise to a Ca(2+) signal that is required for normal, asymmetric expression of genes involved in the specification of body left-right laterality (By similarity). {ECO:0000250|UniProtKB:O35245, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:27991905, ECO:0000305}.;
- Disease
- DISEASE: Polycystic kidney disease 2 with or without polycystic liver disease (PKD2) [MIM:613095]: An autosomal dominant disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy. {ECO:0000269|PubMed:10411676, ECO:0000269|PubMed:10541293, ECO:0000269|PubMed:10835625, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:11968093, ECO:0000269|PubMed:12707387, ECO:0000269|PubMed:14993477, ECO:0000269|PubMed:15772804, ECO:0000269|PubMed:21115670, ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:9326320}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Polycystic Kidney Disease Pathway;VxPx cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.314
Intolerance Scores
- loftool
- 0.366
- rvis_EVS
- -0.71
- rvis_percentile_EVS
- 14.71
Haploinsufficiency Scores
- pHI
- 0.865
- hipred
- Y
- hipred_score
- 0.639
- ghis
- 0.572
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.821
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pkd2
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; liver/biliary system phenotype; embryo phenotype; renal/urinary system phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; respiratory system phenotype;
Zebrafish Information Network
- Gene name
- pkd2
- Affected structure
- thoracic duct
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- branching involved in ureteric bud morphogenesis;liver development;embryonic placenta development;heart looping;detection of nodal flow;calcium ion transport;cell cycle arrest;JAK-STAT cascade;determination of left/right symmetry;heart development;negative regulation of cell population proliferation;spinal cord development;neural tube development;positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity;cellular response to reactive oxygen species;metanephric part of ureteric bud development;sodium ion transmembrane transport;aorta development;regulation of cell population proliferation;cytoplasmic sequestering of transcription factor;positive regulation of nitric oxide biosynthetic process;positive regulation of transcription by RNA polymerase II;detection of mechanical stimulus;release of sequestered calcium ion into cytosol;protein tetramerization;protein homotetramerization;protein heterotetramerization;centrosome duplication;negative regulation of ryanodine-sensitive calcium-release channel activity;placenta blood vessel development;renal tubule morphogenesis;renal artery morphogenesis;calcium ion transmembrane transport;positive regulation of cell cycle arrest;cellular response to calcium ion;cellular response to cAMP;cellular response to hydrostatic pressure;cellular response to osmotic stress;cellular response to fluid shear stress;potassium ion transmembrane transport;determination of liver left/right asymmetry;metanephric mesenchyme development;mesonephric tubule development;mesonephric duct development;metanephric smooth muscle tissue development;metanephric cortex development;metanephric ascending thin limb development;metanephric cortical collecting duct development;metanephric distal tubule development;metanephric S-shaped body morphogenesis;regulation of calcium ion import;inorganic cation transmembrane transport;cell-cell signaling by wnt;negative regulation of G1/S transition of mitotic cell cycle
- Cellular component
- polycystin complex;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;integral component of plasma membrane;cell-cell junction;cilium;basal plasma membrane;membrane;lamellipodium;cytoplasmic vesicle membrane;motile cilium;filamentous actin;cation channel complex;ciliary basal body;basal cortex;ciliary membrane;extracellular exosome;integral component of cytoplasmic side of endoplasmic reticulum membrane;integral component of lumenal side of endoplasmic reticulum membrane;mitotic spindle;non-motile cilium
- Molecular function
- signaling receptor binding;voltage-gated ion channel activity;voltage-gated calcium channel activity;voltage-gated sodium channel activity;voltage-gated potassium channel activity;cation channel activity;calcium channel activity;potassium channel activity;calcium ion binding;protein binding;cytoskeletal protein binding;outward rectifier potassium channel activity;voltage-gated cation channel activity;identical protein binding;protein homodimerization activity;actinin binding;HLH domain binding;ion channel binding;calcium-induced calcium release activity;ATPase binding;phosphoprotein binding;muscle alpha-actinin binding