PKD1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- PKD1 (HGNC:9008) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- polycystin 1, transient receptor potential channel interacting
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- PBP, Pc-1, TRPP1
- %HI
- 28.17(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.18(Read more about gnomAD LOEUF score)
- Cytoband
- 16p13.3
- Genomic Coordinates
-
GRCh37/hg19: chr16:2138709-2185899 NCBI Ensembl UCSC GRCh38/hg38: chr16:2088708-2135898 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001009944.3 ENST00000262304.9 (Read more about MANE Select)
- Function
- Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both PKD1 and PKD2 are required for channel activity (PubMed:27214281). 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 dyna... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-32724
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
06/10/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- polycystic kidney disease 1 Monarch
HI Evidence:
-
PUBMED:
25491204
In 2014, Choi et al. used LR-PCR on 20 unrelated Korean patients diagnosed with autosomal dominant polycystic kidney disease (ADPKD) to identify loss of function variants in PKD1 and PKD2. The results of LR-PCR demonstrated that 10 probands possessed pathogenic loss of function variants in PKD1 as well as a family history of ADPKD; 6 of these probands had frameshift variants, while the other 3 probands had nonsense variants.
-
PUBMED:
24694054
In 2014, Obeidova et al. used methods including LR-PCR, nested PCR, and direct sequencing on 56 unrelated Czech patients diagnosed with autosomal dominant polycystic kidney disease (ADPKD) to identify loss of function variants in PKD1 and PKD2. Their study demonstrated that 37 probands possessed likely pathogenic variants in PKD1. These variants included 11 frameshift variants, 9 nonsense variants, 3 splice variants, and 4 small deletions and insertions in frame. For a group of probands with loss of function variants in PKD1, PKD1 was demonstrated to be the cause of ADPKD in their families through linkage analyses.
-
PUBMED:
29529603
In 2018, Xu et al. used LR-PCR and next generation sequencing (NGS) on 120 Chinese families with at least one family member being diagnosed with autosomal dominant polycystic kidney disease (ADPKD) to describe novel variants in PKD1 and PKD2. The results of LR-PCR and NGS revealed 51 novel variants and 34 known variants in PKD1. These variants included 24 nonsense variants, 32 frameshift variants, 3 in-frame deletions, 2 large deletions, and 5 splices.
HI Evidence Comments:
Heterozygous loss of function mutations in the PKD1 gene cause autosomal dominant polycystic kidney disease (ADPKD) [GeneReviews]. There are several studies reporting the mutation frequency and spectrum in a number of ethnic populations (PMIDs 22237240, 22185115, 19686598, 11571556, 11558899). Partial- or whole-gene deletions have been described in a small number of cases (~4%, GeneReviews).
Large heterozygous deletions, involving the PKD1 and the adjacent TSC2 gene, result in the TSC2/PKD1 contiguous gene syndrome (PKDTS) [PMIDs 22169896, 18818683, 14695542, 17185137). PKDTS has been identified in patients with tuberous sclerosis complex (TSC) and early-onset severe autosomal dominant polycystic kidney disease (ADPKD).
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No literature identified.
Genomic View
Select assembly:
(NC_000016.9)
(NC_000016.10)