Table 1.
Minimal prevalence estimates of cystic kidney and liver diseases by population sequencing
| Gene | Name | Minimal Prevalence a | Putative Function in Cystogenesis | Associated Disease |
|---|---|---|---|---|
| Autosomal dominant inheritance | ||||
| PKD1 | Polycystin-1 | 1 in 1477 | Moves from ER to cilia as complex with polycystin-2. Exact function remains unknown | ADPKD |
| PKD2 | Polycystin-2 | 1 in 3914 | Calcium permeable nonselective cation channel. Forms complex with polycystin-1 | ADPKD |
| GANAB | α-Subunit of glucosidase II | 1 in 4379 | ER enzyme catalyzes hydrolysis of peptide-bound oligosaccharides | ADPKD |
| DNAJB11 | DNAJ heat shock protein 40 subfamily B, member 11 | 1 in 12,312 | ER glycoprotein cofactor for GRP78, required for protein trafficking | ADPKD |
| ALG9 | α-1,2-mannosyltransferase | 1 in 6156 | Enzyme for protein N-glycosylation | ADPKD |
| PRKCSH | Protein Kinase C substrate, 80-kD heavy chain; β-subunit of glucosidase II | 1 in 2077 | ER enzyme catalyzes hydrolysis of peptide-bound oligosaccharides | ADPLD |
| SEC63 | Saccharomyces cerevisiae homolog 63 | 1 in 4684 | With SEC61 and GRP78, assists ER trafficking of membrane-inserted proteins | ADPLD |
| SEC61B | S. cerevisiae homolog 61, β-subunit | 1 in 14,385 | Core of translocon, a transmembrane channel for ER protein translocation | ADPLD |
| ALG8 | α-3-glucosyltransferase | 1 in 1429 | Enzyme for protein N-glycosylation | ADPLD |
| LRP5 | LDL receptor–related protein 5 | 1 in 3099 | Coreceptor required for canonical Wnt signaling | ADPLD |
| TSC1 | Hamartin | 1 in 11,188 | Facilitates HSP90 as chaperone for protein production including Tuberin; negative regulator of mTORC1 | TSC |
| TSC2 | Tuberin | 1 in 2919 | Activating GTPase of mTORC1 downregulators | TSC |
| VHL | VHL tumor suppressor | 1 in 3301 | Oxygen sensing, microtubule orientation, tumor suppression | VHL |
| COL4A1 | Collagen type 4, α1 | 1 in 5594 | Member of mesh-like type 4 basement membrane collagen | HANAC |
| Autosomal recessive inheritance | ||||
| PKHD1 | Polycystic kidney and hepatic disease 1; Fibrocystin | 1 in 201,993 | Noncatalytic β-subunit of glucosidase II | ARPKD |
| DZIP1L | DAZ-interacting zinc finger protein 2 | Approximately 1 in 3 million | Localizes to ciliary transition zone | ARPKD |
| PMM2 | Phosphomannomutase 2 | Approximately 1 in 3 million | Promoter mutation associated with reduced N-glycosylation | HIPKD |
ER, endoplasmic reticulum; ADPKD, autosomal dominant polycystic kidney disease; GRP78, glucose-regulated protein 78 kD; ADPLD, autosomal dominant polycystic liver disease; mTORC1, mammalian target of rapamycin complex 1; HSP90, heat shock protein 90; TSC, tuberous sclerosis complex; VHL, von Hippel-Lindau; HANAC, hereditary angiopathy with nephropathy, aneurysms, and muscle cramps; ARPKD, autosomal recessive polycystic kidney disease; HIPKD, hyperinsulinemic hypoglycemia polycystic kidney disease.
Observed prevalence of protein-truncating mutations from population whole-exome or genome sequencing databases (4). For autosomal recessive conditions, prevalence of homozygous carriers was predicted using the Hardy–Weinberg equilibrium.