Nephronophthisis

Summary

Nephronophthisis (MONDO:0019005) is a disease (an umbrella term covering 18 Mondo subtypes) caused by NPHP3 (GenCC Definitive), with 43 cohort genes and 6 clinical trials. The dominant Reactome pathway is Anchoring of the basal body to the plasma membrane (10 cohort genes).

At a glance

• Prevalence: Unknown (Europe) [Orphanet-validated]
• Causal gene: NPHP3 (GenCC Definitive)
• Umbrella term: 18 Mondo subtypes
• Cohort genes: 43
• ClinVar variants: 9,102
• Phenotypes (HPO): 3
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.25	Finland	Validated

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0007703	Abnormality of retinal pigmentation	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis
Mondo ID	MONDO:0019005
OMIM	256100
Orphanet	655
DOID	DOID:12712
ICD-11	158151813
NCIT	C123200
UMLS	C0687120
MedGen	146912
GARD	0000206
Is cancer (heuristic)	no

Also known as: medullary cystic kidney · nephronophthisis · nephronophthisis (disease)

Data availability: 9,102 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype · 6 cell lines.

Disease family

An umbrella term covering 18 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › nephronophthisis

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Subtypes (18): nephronophthisis 1, nephronophthisis 2, nephronophthisis 3, nephronophthisis 4, nephronophthisis 7, nephronophthisis-like nephropathy 1, nephronophthisis 11, nephronophthisis 12, nephronophthisis 9, nephronophthisis 13, nephronophthisis 14, nephronophthisis 15, nephronophthisis 16, nephronophthisis 18, nephronophthisis 19, nephronophthisis 20, late-onset nephronophthisis, nephronophthisis-like nephropathy 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

376 uncertain significance, 117 likely benign, 45 pathogenic, 33 pathogenic/likely pathogenic, 15 likely pathogenic, 10 conflicting classifications of pathogenicity, 3 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032903	NM_025114.4(CEP290):c.2632del (p.Ile878fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032904	NM_025114.4(CEP290):c.3934A>T (p.Arg1312Ter)	CEP290	Pathogenic	criteria provided, single submitter
1068566	NM_025114.4(CEP290):c.5783del (p.Lys1928fs)	CEP290	Pathogenic	criteria provided, single submitter
1068669	NM_025114.4(CEP290):c.5348_5351del (p.His1783fs)	CEP290	Pathogenic	criteria provided, single submitter
1068974	NM_025114.4(CEP290):c.1400del (p.Asn467fs)	CEP290	Pathogenic	criteria provided, single submitter
1069520	NM_025114.4(CEP290):c.3488_3494dup (p.Val1166fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069579	NM_025114.4(CEP290):c.5235_5238del (p.Ser1745fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069582	NM_025114.4(CEP290):c.4090G>T (p.Glu1364Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1069639	NM_025114.4(CEP290):c.1668del (p.Arg557fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069905	NM_025114.4(CEP290):c.843_845del (p.Tyr281_Gln282delinsTer)	CEP290	Pathogenic	criteria provided, single submitter
1070003	NM_025114.4(CEP290):c.6487dup (p.Met2163fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070079	NM_025114.4(CEP290):c.3022G>T (p.Glu1008Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070250	NM_025114.4(CEP290):c.3925C>T (p.Gln1309Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070282	NM_025114.4(CEP290):c.6418_6419insC (p.Val2140fs)	CEP290	Pathogenic	criteria provided, single submitter
1070346	NM_025114.4(CEP290):c.2254C>T (p.Gln752Ter)	CEP290	Pathogenic	criteria provided, single submitter
1070783	NM_025114.4(CEP290):c.6624del (p.Arg2208fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070890	NM_025114.4(CEP290):c.6645del (p.Glu2216fs)	CEP290	Pathogenic	criteria provided, single submitter
1071036	NM_025114.4(CEP290):c.3708dup (p.Arg1237fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071059	NM_025114.4(CEP290):c.3249dup (p.Arg1084fs)	CEP290	Pathogenic	criteria provided, single submitter
1071060	NM_025114.4(CEP290):c.2506_2507del (p.Glu836fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071061	NM_025114.4(CEP290):c.1987A>T (p.Lys663Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1071206	NM_025114.4(CEP290):c.3310-2A>G	CEP290	Pathogenic	criteria provided, single submitter
1071248	NM_025114.4(CEP290):c.5136_5139del (p.Glu1713fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071318	NM_025114.4(CEP290):c.7287T>A (p.Tyr2429Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071814	NM_025114.4(CEP290):c.355C>T (p.Gln119Ter)	CEP290	Pathogenic	criteria provided, single submitter
1071910	NM_025114.4(CEP290):c.7324G>T (p.Glu2442Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071911	NM_025114.4(CEP290):c.1254_1255del (p.Lys419fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072058	NM_025114.4(CEP290):c.2497del (p.Trp833fs)	CEP290	Pathogenic	criteria provided, single submitter
1072250	NC_000012.11:g.(?88512250)(88519156_?)del	CEP290	Pathogenic	criteria provided, single submitter
1072258	NM_025114.4(CEP290):c.5197C>T (p.Gln1733Ter)	CEP290	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 82 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NPHP3	Definitive	Autosomal recessive	nephronophthisis	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NPHP3	Orphanet:294415	Renal-hepatic-pancreatic dysplasia
NPHP3	Orphanet:3032	NPHP3-related Meckel-like syndrome
NPHP3	Orphanet:3156	Senior-Loken syndrome
NPHP3	Orphanet:93589	Late-onset nephronophthisis
NPHP3	Orphanet:93591	Infantile nephronophthisis
SCN1A	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SCN1A	Orphanet:2382	Lennox-Gastaut syndrome
SCN1A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN1A	Orphanet:33069	Dravet syndrome
SCN1A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN1A	Orphanet:569	Familial or sporadic hemiplegic migraine
ADAMTS9	Orphanet:93592	Juvenile nephronophthisis
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
INVS	Orphanet:3156	Senior-Loken syndrome
INVS	Orphanet:93591	Infantile nephronophthisis
CEP83	Orphanet:93591	Infantile nephronophthisis
WDR19	Orphanet:1515	Cranioectodermal dysplasia
WDR19	Orphanet:3156	Senior-Loken syndrome
WDR19	Orphanet:474	Jeune syndrome
WDR19	Orphanet:93592	Juvenile nephronophthisis
NPHP4	Orphanet:3156	Senior-Loken syndrome
NPHP4	Orphanet:93592	Juvenile nephronophthisis
RMND1	Orphanet:324535	Combined oxidative phosphorylation defect type 11
RMND1	Orphanet:642945	Perrault syndrome type 1
RMND1	Orphanet:642976	Perrault syndrome type 2
AHI1	Orphanet:220493	Joubert syndrome with ocular defect
AHI1	Orphanet:475	Isolated Joubert syndrome
AHI1	Orphanet:791	Retinitis pigmentosa
UBA5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis
CPLANE1	Orphanet:2754	Orofaciodigital syndrome type 6
CPLANE1	Orphanet:475	Isolated Joubert syndrome
CPLANE1	Orphanet:65684	Monomelic amyotrophy
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
NIPBL	Orphanet:199	Cornelia de Lange syndrome
NIPBL	Orphanet:329802	5p13 microduplication syndrome
IQCB1	Orphanet:3156	Senior-Loken syndrome
IQCB1	Orphanet:65	Leber congenital amaurosis
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

43 cohort genes, 40 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	43

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NPHP3	HGNC:7907	ENSG00000113971	Q7Z494	Nephrocystin-3	gencc,clinvar
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
ADAMTS9	HGNC:13202	ENSG00000163638	Q9P2N4	A disintegrin and metalloproteinase with thrombospondin motifs 9	clinvar
SRGAP1	HGNC:17382	ENSG00000196935	Q7Z6B7	SLIT-ROBO Rho GTPase-activating protein 1	clinvar
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
INVS	HGNC:17870	ENSG00000119509	Q9Y283	Inversin	clinvar
CEP83	HGNC:17966	ENSG00000173588	Q9Y592	Centrosomal protein of 83 kDa	clinvar
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	clinvar
NPHP4	HGNC:19104	ENSG00000131697	O75161	Nephrocystin-4	clinvar
RMND1	HGNC:21176	ENSG00000155906	Q9NWS8	Required for meiotic nuclear division protein 1 homolog	clinvar
AHI1	HGNC:21575	ENSG00000135541	Q8N157	Jouberin	clinvar
RBM48	HGNC:21785	ENSG00000127993	Q5RL73	RNA-binding protein 48	clinvar
UBA5	HGNC:23230	ENSG00000081307	Q9GZZ9	Ubiquitin-like modifier-activating enzyme 5	clinvar
NPHP3-AS1	HGNC:24129	ENSG00000248724		NPHP3 antisense RNA 1	clinvar
FAM186B	HGNC:25296	ENSG00000135436	Q8IYM0	Protein FAM186B	clinvar
RLIG1	HGNC:25322	ENSG00000133641	Q8N999	RNA ligase 1	clinvar
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	clinvar
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	clinvar
PIAS1	HGNC:2752	ENSG00000033800	O75925	E3 SUMO-protein ligase PIAS1	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
IQCB1	HGNC:28949	ENSG00000173226	Q15051	IQ calmodulin-binding motif-containing protein 1	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	clinvar
RPGRIP1L	HGNC:29168	ENSG00000103494	Q68CZ1	Protein fantom	clinvar
CEP164	HGNC:29182	ENSG00000110274	Q9UPV0	Centrosomal protein of 164 kDa	clinvar
INTU	HGNC:29239	ENSG00000164066	Q9ULD6	Protein inturned	clinvar
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	clinvar
GLIS2	HGNC:29450	ENSG00000126603	Q9BZE0	Zinc finger protein GLIS2	clinvar
ACAD11	HGNC:30211	ENSG00000240303	Q709F0	Acyl-CoA dehydrogenase family member 11	clinvar
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	clinvar
KIF7	HGNC:30497	ENSG00000166813	Q2M1P5	Kinesin-like protein KIF7	clinvar
AJAP1	HGNC:30801	ENSG00000196581	Q9UKB5	Adherens junction-associated protein 1	clinvar
EVC	HGNC:3497	ENSG00000072840	P57679	EvC complex member EVC	clinvar
TTC21B-AS1	HGNC:41115	ENSG00000224490		TTC21B antisense RNA 1	clinvar
GOLGB1	HGNC:4429	ENSG00000173230	Q14789	Golgin subfamily B member 1	clinvar
NPHP3-ACAD11	HGNC:48351	ENSG00000274810		NPHP3-ACAD11 readthrough (NMD candidate)	clinvar
INCENP	HGNC:6058	ENSG00000149503	Q9NQS7	Inner centromere protein	clinvar
KCNAB2	HGNC:6229	ENSG00000069424	Q13303	Voltage-gated potassium channel subunit beta-2	clinvar
MALL	HGNC:6818	ENSG00000144063	Q13021	MAL-like protein	clinvar
MKKS	HGNC:7108	ENSG00000125863	Q9NPJ1	Molecular chaperone MKKS	clinvar
NCBP1	HGNC:7658	ENSG00000136937	Q09161	Nuclear cap-binding protein subunit 1	clinvar
NPHP1	HGNC:7905	ENSG00000144061	O15259	Nephrocystin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NPHP3	Nephrocystin-3	Required for normal ciliary development and function.
SCN1A	Sodium channel protein type 1 subunit alpha	Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
ADAMTS9	A disintegrin and metalloproteinase with thrombospondin motifs 9	Cleaves the large aggregating proteoglycans, aggrecan (at the ‘1838-Glu-|-Ala-1839’ site) and versican (at the ‘1428-Glu-|-Ala-1429’ site).
SRGAP1	SLIT-ROBO Rho GTPase-activating protein 1	GTPase-activating protein for RhoA and Cdc42 small GTPases.
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
INVS	Inversin	Required for normal renal development and establishment of left-right axis.
CEP83	Centrosomal protein of 83 kDa	Component of the distal appendage region of the centriole involved in the initiation of primary cilium assembly.
WDR19	WD repeat-containing protein 19	As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly.
NPHP4	Nephrocystin-4	Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module.
RMND1	Required for meiotic nuclear division protein 1 homolog	Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome.
AHI1	Jouberin	Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium.
RBM48	RNA-binding protein 48	As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.
UBA5	Ubiquitin-like modifier-activating enzyme 5	E1-like enzyme which specifically catalyzes the first step in ufmylation.
RLIG1	RNA ligase 1	Functions as an RNA ligase, in vitro.
TTC21B	Tetratricopeptide repeat protein 21B	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.
PIAS1	E3 SUMO-protein ligase PIAS1	Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor.
TMEM67	Meckelin	Required for ciliary structure and function.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
IQCB1	IQ calmodulin-binding motif-containing protein 1	Involved in ciliogenesis.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
IFT140	Intraflagellar transport protein 140 homolog	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
RPGRIP1L	Protein fantom	Negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R).
CEP164	Centrosomal protein of 164 kDa	Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells.
INTU	Protein inturned	Plays a key role in ciliogenesis and embryonic development.
CC2D2A	Coiled-coil and C2 domain-containing protein 2A	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
GLIS2	Zinc finger protein GLIS2	Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context.
ACAD11	Acyl-CoA dehydrogenase family member 11	Participates in fatty acid beta-oxidation (FAO) and energy production in the central nervous system (CNS), and to a lesser extent in the liver.
IFT172	Intraflagellar transport protein 172 homolog	Required for the maintenance and formation of cilia.
KIF7	Kinesin-like protein KIF7	Essential for hedgehog signaling regulation: acts both as a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms.
AJAP1	Adherens junction-associated protein 1	Plays a role in cell adhesion and cell migration.
EVC	EvC complex member EVC	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
GOLGB1	Golgin subfamily B member 1	May participate in forming intercisternal cross-bridges of the Golgi complex.
INCENP	Inner centromere protein	Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis.
KCNAB2	Voltage-gated potassium channel subunit beta-2	Regulatory subunit of the voltage-gated potassium (Kv) Shaker channels composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits.
MKKS	Molecular chaperone MKKS	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
NCBP1	Nuclear cap-binding protein subunit 1	Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5’-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene…
NPHP1	Nephrocystin-1	Together with BCAR1 it may play a role in the control of epithelial cell polarity.

Protein-family classification

Druggable: 6 · Difficult: 13 · Unknown: 24 · Druggable fraction: 0.14

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	9	3.6×	0.005
Ion channel	2	5.2×	0.199
Protease	2	1.7×	0.768
Other/Unknown	24	1.0×	0.927
Transcription factor	4	0.8×	0.927
Kinase	1	0.6×	0.927
Enzyme (other)	1	0.3×	0.976

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NPHP3	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, P-loop_NTPase
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
ADAMTS9	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
SRGAP1	Scaffold/PPI	no		RhoGAP_dom, FCH_dom, SH3_domain
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
INVS	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Ankyrin_rpt, Ankyrin_rpt-contain_sf
CEP83	Other/Unknown	no		Centro_Cilium_Assembly
WDR19	Transcription factor	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
NPHP4	Other/Unknown	no		NPHP4, Ig_NPHP4_4th, Ig_NPHP4_3rd
RMND1	Other/Unknown	no		DUF155, RMD1/Sad1-interacting
AHI1	Scaffold/PPI	no		SH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
RBM48	Other/Unknown	no		RBM48_RRM, RBD_domain_sf, RBM48
UBA5	Enzyme (other)	yes	6.2.1.45	ThiF_NAD_FAD-bd, D-isomer_DH_CS1, Ubiquitin-activating_enz
NPHP3-AS1	Other/Unknown	no
FAM186B	Other/Unknown	no		FAM186A_B_N, FAM186A_B_C
RLIG1	Other/Unknown	no		RLIG1
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
PIAS1	Transcription factor	no		SAP_dom, Znf_MIZ, Znf_RING/FYVE/PHD
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
IQCB1	Other/Unknown	no		IQ_motif_EF-hand-BS, ARM-type_fold, P-loop_NTPase
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
RPGRIP1L	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
CEP164	Scaffold/PPI	no		WW_dom, WW_dom_sf, MT-Golgi_org_protein
INTU	Scaffold/PPI	no		PDZ, PDZ_sf, INTU
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf
GLIS2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
ACAD11	Kinase	yes		Aminoglycoside_PTrfase, AcylCoA_DH/ox_M, AcylCo_DH/oxidase_C
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
KIF7	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
AJAP1	Other/Unknown	no		AJAP1_PANP_C, AJAP1
EVC	Other/Unknown	no		Limbin/EVC
TTC21B-AS1	Other/Unknown	no
GOLGB1	Other/Unknown	no		Leu_zip_homeo, GOLGB1
NPHP3-ACAD11	Other/Unknown	no
INCENP	Other/Unknown	no		Inner_centromere_prot_ARK-bd, INCENP_N
KCNAB2	Ion channel	yes		K_chnl_volt-dep_bsu_KCNAB-rel, K_chnl_volt-dep_bsu_KCNAB2, K_chnl_volt-dep_bsu_KCNAB
MALL	Other/Unknown	no		Marvel, MAL, MARVEL-CKLF_proteins
MKKS	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
NCBP1	Other/Unknown	no		MIF4G-like_typ-3, MIF4G-like_typ-1, MIF4G-like_typ-2
NPHP1	Scaffold/PPI	no		SH3_domain, NPHP1_SH3, SH3-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

33 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	43
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	11
right uterine tube	11
sural nerve	9
male germ line stem cell (sensu Vertebrata) in testis	7
bronchial epithelial cell	6
ventricular zone	4
oocyte	4
Brodmann (1909) area 23	3
buccal mucosa cell	3
ganglionic eminence	3
secondary oocyte	3
cortical plate	2
adenohypophysis	2
right lobe of thyroid gland	2
primordial germ cell in gonad	2
pituitary gland	2
left testis	2
endothelial cell	2
metanephros cortex	2
layer of synovial tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NPHP3	254	ubiquitous	marker	superficial temporal artery, layer of synovial tissue, left ovary
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
ADAMTS9	236	broad	marker	omental fat pad, peritoneum, sural nerve
SRGAP1	236	ubiquitous	marker	buccal mucosa cell, cortical plate, medial globus pallidus
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
INVS	215	ubiquitous	yes	calcaneal tendon, adrenal tissue, sural nerve
CEP83	233	ubiquitous	marker	right uterine tube, calcaneal tendon, sural nerve
WDR19	269	ubiquitous	marker	right uterine tube, bronchial epithelial cell, adenohypophysis
NPHP4	165	ubiquitous	marker	right uterine tube, adenohypophysis, right lobe of thyroid gland
RMND1	273	ubiquitous	marker	primordial germ cell in gonad, ganglionic eminence, calcaneal tendon
AHI1	276	ubiquitous	marker	pituitary gland, calcaneal tendon, right hemisphere of cerebellum
RBM48	264	ubiquitous	marker	buccal mucosa cell, secondary oocyte, oocyte
UBA5	287	ubiquitous	marker	body of pancreas, right adrenal gland, right adrenal gland cortex
NPHP3-AS1	59		marker	sural nerve, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
FAM186B	154	tissue_specific	yes	left testis, right testis, testis
RLIG1	288	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, oocyte
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
PIAS1	295	ubiquitous	marker	secondary oocyte, oocyte, seminal vesicle
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
IQCB1	275	ubiquitous	marker	oocyte, epithelium of nasopharynx, nasopharynx
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland
RPGRIP1L	207	ubiquitous	marker	bronchial epithelial cell, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CEP164	261	ubiquitous	marker	sperm, tendon of biceps brachii, male germ cell
INTU	226	ubiquitous	marker	right uterine tube, bronchial epithelial cell, ventricular zone
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
GLIS2	134	ubiquitous	yes	right coronary artery, metanephros cortex, ascending aorta
ACAD11	143	ubiquitous	yes	right lobe of liver, liver, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 65.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NCBP1	3,976
IQCB1	3,562
GOLGB1	3,520
NIPBL	3,278
PIAS1	2,973
INTU	2,947
CEP290	2,778
MKKS	2,728
UBA5	2,500
INCENP	2,408

Intra-cohort edges

A	B	Sources
AHI1	CC2D2A	biogrid_interaction, intact, string_interaction
AHI1	CEP290	string_interaction
AHI1	CPLANE1	string_interaction
AHI1	INVS	string_interaction
AHI1	IQCB1	biogrid_interaction, string_interaction
AHI1	NPHP1	intact, string_interaction
AHI1	NPHP4	string_interaction
AHI1	RPGRIP1L	string_interaction
AHI1	TMEM67	string_interaction
CC2D2A	CEP290	string_interaction
CC2D2A	CPLANE1	string_interaction
CC2D2A	NPHP1	string_interaction
CC2D2A	RPGRIP1L	string_interaction
CC2D2A	TMEM67	string_interaction
CEP164	CEP290	string_interaction
CEP164	CEP83	string_interaction
CEP164	INVS	biogrid_interaction
CEP164	NPHP3	intact
CEP290	INVS	string_interaction
CEP290	IQCB1	biogrid_interaction, intact, string_interaction
CEP290	NPHP1	string_interaction
CEP290	NPHP3	string_interaction
CEP290	NPHP4	string_interaction
CEP290	RPGRIP1L	string_interaction
CEP290	TMEM67	string_interaction
CEP83	TMEM67	string_interaction
CPLANE1	NIPBL	string_interaction
CPLANE1	NPHP1	string_interaction
CPLANE1	TMEM67	string_interaction
EVC	KIF7	string_interaction
EVC	RPGRIP1L	string_interaction
EVC	WDR19	string_interaction
FAM186B	RBM48	string_interaction
GLIS2	INVS	string_interaction
GLIS2	NPHP1	string_interaction
GLIS2	TMEM67	string_interaction
IFT140	IFT172	string_interaction
IFT140	TTC21B	biogrid_interaction, intact, string_interaction
IFT140	WDR19	biogrid_interaction, intact, string_interaction
IFT172	TTC21B	string_interaction
IFT172	WDR19	string_interaction
INTU	NPHP4	intact, string_interaction
INTU	WDR19	string_interaction
INVS	IQCB1	string_interaction
INVS	NPHP1	biogrid_interaction, string_interaction
INVS	NPHP3	string_interaction
INVS	NPHP4	biogrid_interaction, intact, string_interaction
IQCB1	NPHP1	string_interaction
IQCB1	NPHP3	string_interaction
IQCB1	NPHP4	string_interaction

Structural data

PDB: 22 · AlphaFold-only: 18 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NCBP1	Q09161	18
INCENP	Q9NQS7	16
UBA5	Q9GZZ9	12
KIF7	Q2M1P5	5
KCNAB2	Q13303	5
WDR19	Q8NEZ3	4
IFT140	Q96RY7	4
CEP164	Q9UPV0	4
INTU	Q9ULD6	4
KAT6B	Q8WYB5	3
TTC21B	Q7Z4L5	3
NIPBL	Q6KC79	3
NPHP1	O15259	2
NPHP3	Q7Z494	1
SCN1A	P35498	1
AHI1	Q8N157	1
RBM48	Q5RL73	1
PIAS1	O75925	1
TMEM67	Q5HYA8	1
RPGRIP1L	Q68CZ1	1
ACAD11	Q709F0	1
IFT172	Q9UG01	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RLIG1	Q8N999	92.03
MALL	Q13021	90.13
MKKS	Q9NPJ1	89.05
IQCB1	Q15051	83.05
CEP83	Q9Y592	81.90
EVC	P57679	74.49
SRGAP1	Q7Z6B7	73.49
NPHP4	O75161	72.44
INVS	Q9Y283	70.76
RMND1	Q9NWS8	70.28
ADAMTS9	Q9P2N4	69.47
CC2D2A	Q9P2K1	69.46
FAM186B	Q8IYM0	62.65
CEP290	O15078	60.90
GLIS2	Q9BZE0	55.47
AJAP1	Q9UKB5	50.22
CPLANE1	Q9H799
GOLGB1	Q14789

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 149. Enrichment computed across 43 evidence-associated genes (31 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 31 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	10	36.5×	1e-11	CEP83, NPHP4, AHI1, TMEM67, IQCB1, CEP290, RPGRIP1L, CEP164 (+2 more)
Hedgehog ‘off’ state	7	40.3×	1e-08	WDR19, TTC21B, IFT140, RPGRIP1L, INTU, IFT172, KIF7
Cilium Assembly	8	28.1×	1e-08	CEP83, AHI1, TMEM67, IQCB1, CEP290, CEP164, CC2D2A, MKKS
Organelle biogenesis and maintenance	8	17.0×	5e-07	CEP83, AHI1, TMEM67, IQCB1, CEP290, CEP164, CC2D2A, MKKS
Intraflagellar transport	4	25.9×	5e-04	WDR19, TTC21B, IFT140, IFT172
Trafficking of myristoylated proteins to the cilium	1	73.7×	0.163	NPHP3
Transport of Mature mRNAs Derived from Intronless Transcripts	1	52.6×	0.163	NCBP1
Inactivation of CDC42 and RAC1	1	46.0×	0.163	SRGAP1
SLBP independent Processing of Histone Pre-mRNAs	1	36.8×	0.163	NCBP1
Cohesin Loading onto Chromatin	1	36.8×	0.163	NIPBL
Processing of Capped Intronless Pre-mRNA	1	33.5×	0.163	NCBP1
SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	1	33.5×	0.163	NCBP1
Centrosome maturation	2	16.4×	0.163	CEP290, CEP164
Signaling by Hedgehog	2	11.9×	0.163	INTU, KIF7
Loss of Nlp from mitotic centrosomes	2	10.2×	0.163	CEP290, CEP164
Loss of proteins required for interphase microtubule organization from the centrosome	2	10.2×	0.163	CEP290, CEP164
Hedgehog ‘on’ state	2	10.2×	0.163	KIF7, EVC
AURKA Activation by TPX2	2	9.8×	0.163	CEP290, CEP164
Recruitment of mitotic centrosome proteins and complexes	2	8.8×	0.163	CEP290, CEP164
Regulation of PLK1 Activity at G2/M Transition	2	8.2×	0.163	CEP290, CEP164
Mitotic G2-G2/M phases	2	8.2×	0.163	CEP290, CEP164
G2/M Transition	2	8.2×	0.163	CEP290, CEP164
Signaling by ROBO receptors	2	8.0×	0.163	SRGAP1, NCBP1
Recruitment of NuMA to mitotic centrosomes	2	7.5×	0.163	CEP290, CEP164
Mitotic Prometaphase	3	6.7×	0.163	CEP290, CEP164, INCENP
M Phase	3	6.4×	0.163	CEP290, CEP164, INCENP
Cell Cycle, Mitotic	3	4.7×	0.163	CEP290, CEP164, INCENP
Axon guidance	3	4.4×	0.163	SCN1A, SRGAP1, NCBP1
Nervous system development	3	4.2×	0.179	SCN1A, SRGAP1, NCBP1
Regulation of IFNG signaling	1	26.3×	0.186	PIAS1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 39 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium assembly	15	28.3×	4e-16	NPHP3, CEP83, WDR19, AHI1, TTC21B, CPLANE1, TMEM67, IQCB1 (+7 more)
non-motile cilium assembly	8	59.6×	1e-10	NPHP3, CEP290, IFT140, RPGRIP1L, INTU, CC2D2A, IFT172, MKKS
regulation of smoothened signaling pathway	4	64.0×	3e-05	TTC21B, IFT140, RPGRIP1L, INTU
determination of left/right symmetry	5	32.7×	3e-05	NPHP3, IFT140, RPGRIP1L, CC2D2A, MKKS
positive regulation of smoothened signaling pathway	4	43.2×	1e-04	INTU, IFT172, KIF7, EVC
smoothened signaling pathway	5	23.2×	1e-04	TTC21B, INTU, CC2D2A, IFT172, EVC
convergent extension involved in gastrulation	2	432.1×	2e-04	NPHP3, MKKS
intraciliary retrograde transport	3	86.4×	2e-04	WDR19, TTC21B, IFT140
photoreceptor cell maintenance	4	36.8×	2e-04	NPHP3, NPHP4, IQCB1, MKKS
photoreceptor cell outer segment organization	3	81.0×	2e-04	NPHP4, AHI1, IFT140
kidney development	5	18.0×	2e-04	NPHP3, INVS, CEP290, RPGRIP1L, CC2D2A
ear morphogenesis	2	216.1×	8e-04	WDR19, NIPBL
motile cilium assembly	3	44.7×	1e-03	AHI1, INTU, CC2D2A
maintenance of animal organ identity	2	172.8×	0.001	NPHP3, IQCB1
visual behavior	2	144.0×	0.002	NPHP4, NPHP1
neural tube patterning	2	144.0×	0.002	IFT140, RPGRIP1L
negative regulation of smoothened signaling pathway	3	35.0×	0.002	GLIS2, IFT172, KIF7
protein localization to ciliary transition zone	2	123.5×	0.002	NPHP4, CC2D2A
positive regulation of bicellular tight junction assembly	2	86.4×	0.004	NPHP4, NPHP1
heart looping	3	20.6×	0.007	NPHP3, IFT172, MKKS
embryonic camera-type eye development	2	61.7×	0.007	WDR19, IFT140
gonad development	2	57.6×	0.008	WDR19, MKKS
establishment of planar polarity	2	54.0×	0.008	RPGRIP1L, INTU
embryonic brain development	2	41.1×	0.014	IFT140, CC2D2A
fat cell differentiation	3	13.9×	0.016	PIAS1, NIPBL, MKKS
negative regulation of keratinocyte proliferation	2	36.0×	0.017	INTU, IFT172
regulation of polarized epithelial cell differentiation	1	432.1×	0.021	AJAP1
external genitalia morphogenesis	1	432.1×	0.021	NIPBL
hindgut development	1	432.1×	0.021	IFT172
determination of intestine left/right asymmetry	1	432.1×	0.021	NPHP3

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 39

Druggability breadth: 8 of 43 evidence-associated genes (19%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN1A	MEXILETINE HYDROCHLORIDE
ACAD11	ERLOTINIB
INCENP	INAMRINONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1A	94	4
INCENP	7	4
ACAD11	3	4
NCBP1	1	2
NPHP3	0	0
ADAMTS9	0	0
SRGAP1	0	0
KAT6B	0	0
INVS	0	0
CEP83	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
INCENP	49	Binding:49
KAT6B	22	Binding:20, Functional:2
NCBP1	8	Binding:8
KIF7	5	Binding:5
UBA5	2	Binding:2
ACAD11	2	Binding:2
KCNAB2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6B	2.3.1.48	histone acetyltransferase
UBA5	6.2.1.45	E1 ubiquitin-activating enzyme

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN1A	149

Pharmacogenomics

Cohort genes with a PharmGKB record: 41; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	SCN1A, ACAD11, INCENP
B	Phased (≥1) drug, not yet approved	1	NCBP1
C	Druggable family + PDB, no drug	2	UBA5, KCNAB2
D	Druggable family + AlphaFold only, no drug	2	ADAMTS9, CC2D2A
E	Difficult family or no structure, no drug	35	NPHP3, SRGAP1, KAT6B, INVS, CEP83, WDR19, NPHP4, RMND1, AHI1, RBM48 (+25 more)

Undrugged target profiles

39 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
NPHP3	0	—
ADAMTS9	0	—
SRGAP1	0	—
KAT6B	22	—
INVS	0	—
CEP83	0	—
WDR19	0	—
NPHP4	0	—
RMND1	0	—
AHI1	0	—
RBM48	0	—
UBA5	2	—
NPHP3-AS1	0	—
FAM186B	0	—
RLIG1	0	—
TTC21B	0	—
CPLANE1	0	—
PIAS1	0	—
TMEM67	0	—
NIPBL	0	—
IQCB1	0	—
CEP290	0	—
IFT140	0	—
RPGRIP1L	0	—
CEP164	0	—
INTU	0	—
CC2D2A	0	—
GLIS2	0	—
IFT172	0	—
KIF7	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies
NCT01022957	Not specified	COMPLETED	Nephronophthisis : Clinical and Genetic Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05286632	Not specified	COMPLETED	KidneYou - Innovative Digital Therapy