Table 2.
Summary of NPHP1-NPHP11 genes, gene products, chromosomal localization, phenotypes, extrarenal symtoms, and mutation frequency of nephrocystins [12,53].
| Gene (protein) | Chromosome | Phenotype (median age at ESRF) | Extrarenal symptoms | Mutation frequency | Interaction partners |
|---|---|---|---|---|---|
| NPHP1 (nephrocystin-1) | 2q13 | NPHP (13yrs) | RP (10%),OMA (2%), JS (rarely) | 23.4% homozygous deletion 2.1% point mutation |
Inversin, nephrocystin- 3, nephrocystin-4, filamin A and B, tensin, β-tubulin, PTK2B |
| NPHP2/INVS (inversin) | 9q31 | Infantile NPHP(<5yrs) | RP (10%), LF, situs inversus, VSD | 1.4% | Nephrocystin-1, calmodulin, catenins, β-tubulin, APC2 |
| NPHP3 (nephrocystin-3) | 3q22 | Infantile and adolescent NPHP | LF, RP (10%), situs inversus, MKS | 0.7% If truncating mutation infantile form |
Nephrocystin-1 |
| NPHP4 (nephrocystin-4) | 1p36 | NPHP (21 yrs) | RP (10%), OMA, LF | 2.6% | Nephrocystin-1, BCAR1, PTK2B |
| NPHP5/IQCB1 (nephrocystin-5) | 3q21 | NPHP (13 years) | Early-onset RP | 3.6% | Calmodulin, RPGR, nephrocystin-6 |
| NPHP6/CEP290 (nephrocystin-6/CEP290) | 12q21 | NPHP | JS, MKS | 1% | ATF4, nephrocystin-5, CC2D2A |
| NPHP7/GLIS2(nephrocystin -7/GLIS2) | 16p | NPHP | _ | 0.1% | _ |
| NPHP8/RPGRIP1L (nephrocystin-8/RPGRIP1L) | 16q | NPHP | JS, MKS | 0.5% | Nephrocystin-1 |
| NPHP9/NEK8 (nephrocystin-9/NEK8) | 17q11 | Infantile NPHP | _ | 0.1% | _ |
| TMEM67/MKS3/NPHP11 (Meckelin/nephrocystin-11) | 8q22.1 | MKS, JS, NPHP+LF | JS, MKS | ||
| NPHP1L/XPNPEP3 (nephrocystin-1L/XPNPEP3) | 22q13 | NPHP | Cardiomyopathy, seizures | 0.1% |
ATF4, activating transcription factor 4;APC2, anap hase-promoting complex 2; BCAR1, breast cancer anti-estrogen resistance 1;CC2D2A, coiled-coil and C2 domain containing 2A;JS, Joubert syndrome; LF, liver fibrosis; MKS, Meckel-Gruber syndrome; OMA,oculomotor apraxia; PTK2B, protein tyrosine kinase 2B; RP, retinitis pigmentosa; RPGR, retinitis pigmentosa GTPase regulator; VSD, ventricular septal defect