PKHD1

PKHD1 ciliary IPT domain containing fibrocystin/polyductin, the group of IPT domain containing

Basic information

Region (hg38): 6:51615299-52087613

Previous symbols: [ "TIGM1" ]

Links

ENSG00000170927 ∙ NCBI:5314 ∙ OMIM:606702 ∙ HGNC:9016 ∙ Uniprot:P08F94 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive polycystic kidney disease (Definitive), mode of inheritance: AR
• polycystic kidney disease 4 (Definitive), mode of inheritance: AR
• polycystic kidney disease 4 (Strong), mode of inheritance: AR
• polycystic kidney disease 4 (Strong), mode of inheritance: AR
• polycystic kidney disease 4 (Definitive), mode of inheritance: AR
• autosomal recessive polycystic kidney disease (Supportive), mode of inheritance: AR
• Caroli disease (Supportive), mode of inheritance: AR
• 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 4 with or without polycystic liver disease	AR	Allergy/Immunology/Infectious; Gastrointestinal; Pulmonary; Pharmacogenomic; Renal	Initially, neonates may require interventions related to compromises in respiratory and renal function, including surgical interventions and dialysis as necessary (renal transplant may be indicated as well); Surveillance and interventions for complications related to systemic and portal hypertension can be beneficial; Medical treatment (eg, with ACE inhibitors or ARBs) can be beneficial; Other interventions, such as nutritional and endocrinological (eg, GH treatment) support may be beneficial; Prophylaxis against specific infectious agents is indicated; Certain types of medications, such as sympathomimetic or nephrotoxic agents should be avoided or used judiciously if necessary	Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Renal	13764315; 4688793; 2702087; 7554350; 11919560; 12506140; 12728091; 15108277; 15706593; 16523049; 21896375; 20301501; 21046169; 22464505; 22882926; 23041322; 23941846; 24114580; 24162162

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKHD1 gene.

• Autosomal recessive polycystic kidney disease (304 variants)
• Polycystic kidney disease 4 (81 variants)
• not provided (39 variants)
• PKHD1-related disorder (9 variants)
• Autosomal dominant polycystic liver disease (6 variants)
• Polycystic kidney disease (3 variants)
• See cases (2 variants)
• Enlarged kidney;Hyperechogenic kidneys;Multiple renal cysts;Anhydramnios (2 variants)
• Enlarged kidney;Hyperechogenic kidneys;Anhydramnios (1 variants)
• Ventricular hypertrophy;Renal cyst;Polycystic kidney disease (1 variants)
• Autosomal dominant polycystic kidney disease (1 variants)
• Hypoplastic aortic arch;Polycystic kidney disease (1 variants)
• Abnormality of the genitourinary system (1 variants)
• Abnormal intrahepatic bile duct morphology (1 variants)
• Anhydramnios;Hyperechogenic kidneys;Multiple renal cysts;Enlarged kidney (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKHD1 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			14	1488	18	1520
missense	14	119	859	44	15	1051
nonsense	113	142	9			264
start loss	1	1				2
frameshift	200	282	3			485
inframe indel	1	3	30			34
splice donor/acceptor (+/-2bp)	15	152	4			171
splice region	1	7	35	207	3	253
non coding		1	68	603	177	849
Total	344	700	987	2135	210

Highest pathogenic variant AF is 0.000618

Variants in PKHD1

This is a list of pathogenic ClinVar variants found in the PKHD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-51615561-A-G		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51615568-GAATT-G		Autosomal recessive polycystic kidney disease	Uncertain significance (Jun 14, 2016)
6-51615637-C-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51615688-G-T		Autosomal recessive polycystic kidney disease	Benign (Jan 13, 2018)
6-51615702-T-C		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51615736-A-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51615758-A-G		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51615812-G-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51615910-T-C		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51615943-C-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51616037-T-A		Autosomal recessive polycystic kidney disease	Likely benign (Jan 13, 2018)
6-51616051-T-C		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51616055-T-C		Autosomal recessive polycystic kidney disease	Benign (Jan 12, 2018)
6-51616056-G-A		Autosomal recessive polycystic kidney disease	Benign (Jan 12, 2018)
6-51616105-G-A		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51616114-A-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51616159-A-G		Autosomal recessive polycystic kidney disease	Uncertain significance (Jun 14, 2016)
6-51616224-T-G		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 13, 2018)
6-51616365-G-C		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51616415-C-T		Autosomal recessive polycystic kidney disease	Likely benign (Jan 13, 2018)
6-51616416-G-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51616501-G-T		Autosomal recessive polycystic kidney disease	Uncertain significance (Jan 12, 2018)
6-51616517-T-C		Autosomal recessive polycystic kidney disease	Benign (Jan 13, 2018)
6-51616527-A-AT		Autosomal recessive polycystic kidney disease	Uncertain significance (Jun 14, 2016)
6-51616527-A-ATT		Autosomal recessive polycystic kidney disease	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PKHD1	protein_coding	protein_coding	ENST00000371117	66	472326

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.17e-47	1.00	125106	0	642	125748	0.00256

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.982	2245	2.12e+3	1.06	0.000115	26495
Missense in Polyphen		560	588.92	0.95089		7885
Synonymous	-0.560	829	809	1.03	0.0000462	8254
Loss of Function	5.28	107	184	0.580	0.00000992	2196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00455	0.00442
Ashkenazi Jewish	0.00747	0.00747
East Asian	0.00103	0.00103
Finnish	0.00721	0.00723
European (Non-Finnish)	0.00186	0.00182
Middle Eastern	0.00103	0.00103
South Asian	0.00167	0.00167
Other	0.00229	0.00228

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be required for correct bipolar cell division through the regulation of centrosome duplication and mitotic spindle assembly. May be a receptor protein that acts in collecting-duct and biliary differentiation. {ECO:0000269|PubMed:20554582}.
• Disease: DISEASE: Note=Loss-of-function PKHD1 variations may cause autosomal dominant polycystic liver disease (PCLD) in patients that lack variations in known causative genes, such as PRKCSH and SEC63. {ECO:0000269|PubMed:28375157}.

Recessive Scores

• pRec: 0.255

Intolerance Scores

• loftool: 0.00772
• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.51

Haploinsufficiency Scores

• pHI: 0.0820
• hipred: N
• hipred_score: 0.324

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0854

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pkhd1
• Phenotype: cellular phenotype; endocrine/exocrine gland 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); growth/size/body region 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); digestive/alimentary 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); renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Biological process: kidney development;cellular calcium ion homeostasis;positive regulation of cell population proliferation;regulation of centrosome duplication;regulation of TOR signaling;negative regulation of NF-kappaB transcription factor activity;homeostatic process;negative regulation of apoptotic process;negative regulation of cellular component movement;negative regulation of protein kinase B signaling;cilium assembly;regulation of ERK1 and ERK2 cascade;cell-cell adhesion
• Cellular component: chromosome, centromeric region;cytoplasm;centrosome;cilium;integral component of membrane;apical plasma membrane;anchored component of external side of plasma membrane;ciliary basal body;perinuclear region of cytoplasm;extracellular exosome;mitotic spindle
• Molecular function: protein binding;signaling receptor activity