Table 1.

Summary of the current knowledge of DAP genes in relation to human molecular genetics, including its phenotypic description and available animal models.

Gene	Mutations	Renal Phenotype	Extra-Renal Manifestations	Cilia Phenotype	Ref.
CEP83	Hs In 9 individuals diagnosed with NPHP-RC homozygous or compound heterozygous CEP83 mutations has been identified. 1 individual has been reported with a homozygous missense, 1 with a homozygous protein-truncating mutation. 7 individuals carry at least one loss of function allele.	Nephronophthisis, Tubulointerstitial nephritis, Corticomedullary cysts, Tubular atrophy, and End-stage renal disease.	Eye (in some patients): Retinitis Strabismus Liver (in some patients): Cholestasis, Hepatic cytolysis, Portal fibrosis Central Nervous System (in some patients): Intellectual disability, Hydrocephalus.	(a) primary fibroblasts:impaired ciliation (b) renal biopsy sample: increased ciliary length (c) overexpression of disease construct in RPE-1/ IMCD3: abolished centrosomal localization of CEP83 abrogated protein interaction with CEP164 and IFT20 nuclear accumulation of CEP83 (d) depletion in RPE-1: abolished cilia formation.	[36]
Cep83	Mm Selective deletion of Cep83 in cortical radial glial progenitors (RGPs).		Enlarged brain with abnormal folding.	RGPs lacking Cep83 display a lack of primary cilia.	[96]
cep83	Dr Morpholino-mediated knockdown of ccdc41 (CEP83 ortholog in Zebrafish).		No defect in left/right body asymmetry was observed.	Olfactory placodes showed reduction in cilium formation.	[100]
CEP164	Hs Homozygous and compound heterozygous has been identified in 4 individuals with NPHP-RC. 2 individuals carried loss of function mutations. Compound heterozygous missense mutations lead to Bardet–Biedl syndrome in 1 individual and a homozygous loss mutation to primary ciliary dyskinesia (PCD) in 1 individual.	Nephronophthisis	Eyes: Retinal degeneration, Leber congenital amaurosis, Nystagmus (in 2 patients) Liver (in some patients): Liver failure Central Nervous System: Developmental delay (in 1 patient), Seizures (in 1 patient), Cerebellar vermis hypoplasia (in 1 patient) Skeletal: Polydactyly (in 2 patients) Obesity (in 2 patients) Short stature (in 1 patient) Bilateral bronchiectasis (in 1 patient).	(a) Overexpression of disease construct in IMCD3 cells: abolished centrosomal localization (b) Overexpression of disease construct in hTERT RPE: compromise interaction with TTBK2 (c) Depletion in RPE-1: abolish cilia formation.	[101,102,103,104,105]
cep164	Dr	Pronephric tubule cysts.	Abnormal heart looping, hydrocephalus, and retinal dysplasia.	n/a	[102]
Cep164	Mm	Only in the collecting duct-specific deletion of CEP164 mice: Cystic kidneys [40].	(a) Global CEP164 deficiency mice: early embryonic lethality, holoprosencephaly, cardiac looping defects, and a truncated posterior trunk [106]. (b) collecting duct-specific deletion of CEP164 mice: only renal cyst growth. (c) CEP164 loss in FOXJ1-positive tissues in mice: results in hydrocephalus.	(a) Global deficiency: abolish cilia formation in neuronal tube (b) Collecting duct-specific deletion: abolishes primary cilia formation in epithelial cells (c) FOXJ1-specific deletion:reduction number of l multiciliated cells.	[40,106]
SCLT1	Hs Compound heterozygous missense mutations has been reported in 1 individual with oro-facio-digital syndrome. Biallelic loss of function mutations have been identified in 1 individual withSenior-Løken syndrom, and in 1 individual with Bardet–Biedl syndrome.	Nephronophthisis (1 patient) bilateral hyperechogenicity, cortico-medullary renal cysts (1 Patient) ESRD at 11 years of age (1 Patient).	(a) Orofaciodigital syndrome type IX (OFD type IX) (2 patients): midline cleft, microcephaly, colobomatous microphthalmia/ anophthalmia, polydactyly, absent pituitary, and congenital heart disease. (b) Senior–Løken syndrome (1 patient): Nystagmus, hepatic dysfunction, megacystis, mild learning disability, autism, obesity (c) Bardet–Biedl syndrome (2 patients): intellectual disability, autism, and motor developmental delay, hepatic fibrosis, short stature, truncal obesity, retinitis pigmentosa.	(a) Depletion in RPE-1: abolish cilia formation.	[107,108]
Sclt1	Mm	Cystic kidneys	Cleft palate and polydactyly.	Global deficiency: disrupted cilia assembly.	[37,38,108]

Note: Hs, Homo sapiens; Mm, Mus musculus; Dr, Danio rerio.