PKD1

polycystin 1, transient receptor potential channel interacting, the group of MicroRNA protein coding host genes|C-type lectin domain containing

Basic information

Region (hg38): 16:2088707-2135898

Links

ENSG00000008710 ∙ NCBI:5310 ∙ OMIM:601313 ∙ HGNC:9008 ∙ Uniprot:P98161 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polycystic kidney disease 1 (Strong), mode of inheritance: AD
• Caroli disease (Strong), mode of inheritance: AD
• polycystic kidney disease 1 (Strong), mode of inheritance: AD
• polycystic kidney disease 1 (Definitive), mode of inheritance: AD
• autosomal dominant polycystic kidney disease (Supportive), mode of inheritance: AD
• autosomal dominant polycystic kidney disease (Definitive), mode of inheritance: AD
• autosomal recessive polycystic kidney disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polycystic kidney disease 1 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	13723091; 5641158; 6102642; 6766288; 6835317; 3419455; 2198396; 1670785; 1513348; 1583643; 8004675; 7633405; 9650770; 11359016; 11134267; 11752048; 12842373; 12900587; 15458452; 15086900; 12631134; 14581387; 15034105; 14531813; 17699192; 16354965; 17699202; 16707749; 17035604; 16775462; 18299682; 17699395; 17533013; 17434405; 19443633; 19470662; 20301424; 20219616; 21551026; 21544064; 21333426

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKD1 gene.

• not provided (1463 variants)
• Polycystic kidney disease, adult type (1244 variants)
• not specified (386 variants)
• Polycystic kidney disease (342 variants)
• Inborn genetic diseases (319 variants)
• PKD1-related condition (169 variants)
• Autosomal dominant polycystic kidney disease (157 variants)
• Polycystic kidney disease 3 with or without polycystic liver disease (6 variants)
• Tuberous sclerosis syndrome (5 variants)
• - (4 variants)
• See cases (3 variants)
• Autosomal recessive polycystic kidney disease (3 variants)
• Bile duct cancer (3 variants)
• Polycystic liver disease 1 (2 variants)
• Chronic kidney disease (2 variants)
• Hypertensive disorder;Polycystic kidney disease (2 variants)
• Autosomal dominant polycystic kidney disease;Polycystic kidney disease, adult type (1 variants)
• Lymphangiomyomatosis;Isolated focal cortical dysplasia type II;Tuberous sclerosis 2 (1 variants)
• Bladder exstrophy-epispadias-cloacal extrophy complex (1 variants)
• Renal cyst;Proteinuria (1 variants)
• Renal cyst (1 variants)
• Polycystic kidney disease;Enlarged kidney;Hemangioma (1 variants)
• Multiple renal cysts;Anhydramnios (1 variants)
• Polycystic kidney disease;Hyperechogenic kidneys;Clubfoot;Narrow chest (1 variants)
• Enlarged kidney;Hyperechogenic kidneys;Multiple renal cysts;Anhydramnios (1 variants)
• Polycystic kidney disease;Polycystic liver disease 1 (1 variants)
• Multiple renal cysts;Pancreatic cysts;Hepatic cysts (1 variants)
• 3-4 toe syndactyly;Moderate sensorineural hearing impairment;Polycystic kidney disease (1 variants)
• Abnormality of the kidney;Multicystic kidney dysplasia;Polycystic kidney disease (1 variants)
• Hyperechogenic kidneys;Narrow chest;Clubfoot;Polycystic kidney disease (1 variants)
• Polycystic kidney disease;Polycystic liver disease 1;Cystic renal dysplasia;Multicystic kidney dysplasia (1 variants)
• Hypertensive disorder;Renal cyst;Pancreatic cysts;Hepatic cysts;Renovascular hypertension (1 variants)
• Hepatic cysts;Stage 5 chronic kidney disease;Dilatation of the cerebral artery (1 variants)
• Polycystic kidney disease;Elevated circulating creatine kinase concentration;Lower limb muscle weakness;Achilles tendon contracture;Lower limb amyotrophy (1 variants)
• 12 conditions (1 variants)
• Hypertensive disorder;Multiple renal cysts (1 variants)
• Renal insufficiency;Polycystic kidney disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKD1 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	1		25	223	68	317
missense	5	73	1013	117	18	1226
nonsense	224	46	1			271
start loss	1					1
frameshift	272	72	2			346
inframe indel	1	34	47			82
splice donor/acceptor (+/-2bp)	49	34	1			84
splice region	1	2	34	22	5	64
non coding	1	6	12	52	63	134
Total	554	265	1101	392	149

Highest pathogenic variant AF is 0.0000329

Variants in PKD1

This is a list of pathogenic ClinVar variants found in the PKD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-2088737-T-C		Tuberous sclerosis syndrome	Likely benign (Jun 18, 2018)
16-2088737-T-G		Tuberous sclerosis syndrome	not provided (-)
16-2088738-G-A		Tuberous sclerosis syndrome	not provided (-)
16-2088750-CG-C		Tuberous sclerosis syndrome	Likely benign (Sep 25, 2018)
16-2088757-T-TG		Tuberous sclerosis syndrome	not provided (-)
16-2088865-TCGCG-T			Likely benign (Oct 17, 2019)
16-2088866-C-T			Benign (Jun 19, 2018)
16-2088868-C-T			Benign (Jun 14, 2018)
16-2088872-T-TGCGC			Likely benign (Aug 15, 2019)
16-2088879-G-GCA			Likely benign (Sep 09, 2019)
16-2088881-GCA-G			Likely benign (Aug 21, 2019)
16-2088881-GCACA-G			Benign (Aug 12, 2019)
16-2088881-GCACACA-G		not specified	Benign (Aug 12, 2019)
16-2088881-G-GCA			Likely benign (Nov 14, 2019)
16-2088881-G-GCGCACA			Benign (Aug 20, 2019)
16-2088881-G-GCGCACACA			Benign (Aug 21, 2019)
16-2088885-A-G			Likely benign (Aug 06, 2019)
16-2088887-AC-A			Benign (Aug 06, 2019)
16-2088889-AC-A			Likely benign (Aug 10, 2019)
16-2088889-ACAC-A			Benign (Aug 06, 2019)
16-2088891-AC-A			Likely benign (Aug 10, 2019)
16-2089712-C-T		not specified • Polycystic kidney disease, adult type • Autosomal dominant polycystic kidney disease	Benign/Likely benign (Feb 13, 2020)
16-2089717-G-C		PKD1-related disorder	Likely benign (Feb 28, 2024)
16-2089719-A-C		PKD1-related disorder	Likely benign (Sep 28, 2022)
16-2089734-C-T		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PKD1	protein_coding	protein_coding	ENST00000262304	46	47189

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.62e-12	125394	0	34	125428	0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-4.32	3329	2.70e+3	1.23	0.000208	26961
Missense in Polyphen		745	793.89	0.93841		8642
Synonymous	-17.9	2103	1.29e+3	1.63	0.000110	9531
Loss of Function	9.96	18	149	0.121	0.00000731	1597

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000179	0.000178
Ashkenazi Jewish	0.00	0.00
East Asian	0.000499	0.000490
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000184	0.000132
Middle Eastern	0.000499	0.000490
South Asian	0.0000985	0.0000980
Other	0.000174	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in renal tubulogenesis (PubMed:12482949). Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). Acts as a regulator of cilium length, together with PKD2 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling (By similarity). 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 (By similarity). May be an ion-channel regulator. Involved in adhesive protein-protein and protein- carbohydrate interactions. {ECO:0000250|UniProtKB:O08852, ECO:0000269|PubMed:12482949}.
• Disease: DISEASE: Polycystic kidney disease 1 with or without polycystic liver disease (PKD1) [MIM:173900]: An autosomal dominant disorder characterized by renal cysts, liver cysts and intracranial aneurysm. Clinical variability is due to differences in the rate of loss of glomerular filtration, the age of reaching end-stage renal disease and the occurrence of hypertension, symptomatic extrarenal cysts, and subarachnoid hemorrhage from intracranial 'berry' aneurysm. {ECO:0000269|PubMed:10200984, ECO:0000269|PubMed:10364515, ECO:0000269|PubMed:10577909, ECO:0000269|PubMed:10647901, ECO:0000269|PubMed:10729710, ECO:0000269|PubMed:10854095, ECO:0000269|PubMed:10923040, ECO:0000269|PubMed:10987650, ECO:0000269|PubMed:11012875, ECO:0000269|PubMed:11058904, ECO:0000269|PubMed:11115377, ECO:0000269|PubMed:11216660, ECO:0000269|PubMed:11316854, ECO:0000269|PubMed:11558899, ECO:0000269|PubMed:11571556, ECO:0000269|PubMed:11691639, ECO:0000269|PubMed:11773467, ECO:0000269|PubMed:11857740, ECO:0000269|PubMed:11967008, ECO:0000269|PubMed:12007219, ECO:0000269|PubMed:12070253, ECO:0000269|PubMed:12220456, ECO:0000269|PubMed:12482949, ECO:0000269|PubMed:12842373, ECO:0000269|PubMed:15772804, ECO:0000269|PubMed:18837007, ECO:0000269|PubMed:21115670, ECO:0000269|PubMed:22508176, ECO:0000269|PubMed:8554072, ECO:0000269|PubMed:9199561, ECO:0000269|PubMed:9259200, ECO:0000269|PubMed:9285784, ECO:0000269|PubMed:9521593, ECO:0000269|PubMed:9921908}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Polycystic Kidney Disease Pathway;Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway;GPR40 Pathway;EMT transition in Colorectal Cancer;VxPx cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Haploinsufficiency Scores

• pHI: 0.719
• hipred: Y
• hipred_score: 0.683
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.618

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pkd1
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; reproductive system phenotype; normal phenotype; 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); 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); neoplasm; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: pkd1a
• Affected structure: thoracic duct
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: cartilage condensation;in utero embryonic development;kidney development;liver development;embryonic placenta development;protein export from nucleus;cell cycle arrest;homophilic cell adhesion via plasma membrane adhesion molecules;cell-matrix adhesion;calcium-independent cell-matrix adhesion;positive regulation of cytosolic calcium ion concentration;JAK-STAT cascade;heart development;anatomical structure morphogenesis;Wnt signaling pathway;peptidyl-serine phosphorylation;spinal cord development;neural tube development;establishment of cell polarity;regulation of cell adhesion;positive regulation of protein binding;response to fluid shear stress;lymph vessel morphogenesis;cytoplasmic sequestering of transcription factor;skin development;positive regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of transcription by RNA polymerase II;digestive tract development;branching morphogenesis of an epithelial tube;genitalia development;detection of mechanical stimulus;cartilage development;protein heterotetramerization;regulation of mitotic spindle organization;lung epithelium development;placenta blood vessel development;regulation of proteasomal protein catabolic process;calcium ion transmembrane transport;mesonephric tubule development;mesonephric duct development;metanephric collecting duct development;metanephric ascending thin limb development;metanephric proximal tubule development;metanephric distal tubule morphogenesis;cell-cell signaling by wnt;regulation of G1/S transition of mitotic cell cycle
• Cellular component: Golgi membrane;polycystin complex;nucleus;cytoplasm;endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;cilium;cell surface;integral component of membrane;basolateral plasma membrane;lateral plasma membrane;Golgi-associated vesicle membrane;motile cilium;cation channel complex;calcium channel complex;ciliary membrane;extracellular exosome
• Molecular function: calcium channel activity;protein binding;protein kinase binding;protein domain specific binding;carbohydrate binding;Wnt-activated receptor activity;ion channel binding