Nephronophthisis 15

Summary

Nephronophthisis 15 (MONDO:0013917) is a disease caused by CEP164 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CEP164 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1,447

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis 15
Mondo ID	MONDO:0013917
OMIM	614845
DOID	DOID:0111123
UMLS	C3541853
MedGen	762112
GARD	0015852
Is cancer (heuristic)	no

Also known as: CEP164 nephronophthisis (disease) · nephronophthisis (disease) caused by mutation in CEP164 · nephronophthisis 15 · nephronophthisis type 15 · NPHP15

Data availability: 1,447 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Senior-Loken syndrome › nephronophthisis 15

Related subtypes (8): Senior-Loken syndrome 1, senior-loken syndrome 3, Senior-Loken syndrome 4, Senior-Loken syndrome 5, Senior-Loken syndrome 6, Senior-Loken syndrome 7, Senior-Loken syndrome 8, Senior-Loken syndrome 9

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:

287 uncertain significance, 249 likely benign, 20 conflicting classifications of pathogenicity, 13 likely pathogenic, 12 pathogenic, 9 benign, 6 pathogenic/likely pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1002558	NM_014956.5(CEP164):c.749dup (p.Gly250_Asp251insTer)	CEP164	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1009382	NM_014956.5(CEP164):c.1481dup (p.Pro495fs)	CEP164	Pathogenic	criteria provided, multiple submitters, no conflicts
1015384	NM_014956.5(CEP164):c.2656G>T (p.Gly886Ter)	CEP164	Pathogenic	criteria provided, single submitter
1053450	NM_014956.5(CEP164):c.451C>T (p.Arg151Ter)	CEP164	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179150	NM_014956.5(CEP164):c.1264_1265insTGGCTGG (p.His422fs)	CEP164	Pathogenic	criteria provided, single submitter
1362712	NM_014956.5(CEP164):c.2509C>T (p.Arg837Ter)	CEP164	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1371663	NM_014956.5(CEP164):c.3055C>T (p.Gln1019Ter)	CEP164	Pathogenic	criteria provided, multiple submitters, no conflicts
1379611	NM_014956.5(CEP164):c.3109C>T (p.Gln1037Ter)	CEP164	Pathogenic	criteria provided, single submitter
1405576	NM_014956.5(CEP164):c.2688_2691del (p.Arg897fs)	CEP164	Pathogenic	criteria provided, single submitter
1431411	NM_014956.5(CEP164):c.2942_2943del (p.Glu981fs)	CEP164	Pathogenic	criteria provided, single submitter
1454049	NM_014956.5(CEP164):c.1996G>T (p.Glu666Ter)	CEP164	Pathogenic	criteria provided, single submitter
1454479	NM_014956.5(CEP164):c.3711_3712del (p.Ser1238fs)	CEP164	Pathogenic	criteria provided, single submitter
1454912	NM_014956.5(CEP164):c.1444C>T (p.Gln482Ter)	CEP164	Pathogenic	criteria provided, single submitter
1456625	NM_014956.5(CEP164):c.1669dup (p.Glu557fs)	CEP164	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1475271	NM_014956.5(CEP164):c.4010dup (p.Asp1337fs)	CEP164	Pathogenic	criteria provided, single submitter
1902136	NM_014956.5(CEP164):c.3039_3040dup (p.Gln1014fs)	CEP164	Pathogenic	criteria provided, single submitter
1930533	NM_014956.5(CEP164):c.2535_2536dup (p.Glu846fs)	CEP164	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1935573	NM_014956.5(CEP164):c.4001G>A (p.Trp1334Ter)	CEP164	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1019274	NM_014956.5(CEP164):c.2760+1G>T	CEP164	Likely pathogenic	criteria provided, single submitter
1019779	NM_014956.5(CEP164):c.3749-2A>G	CEP164	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047792	NM_014956.5(CEP164):c.1934+1G>A	CEP164	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1060026	NM_014956.5(CEP164):c.1724+1G>A	CEP164	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1062189	NM_014956.5(CEP164):c.553-1G>A	CEP164	Likely pathogenic	criteria provided, single submitter
1062608	NM_014956.5(CEP164):c.688-2A>C	CEP164	Likely pathogenic	criteria provided, single submitter
1179207	GRCh37/hg19 11q23.3(chr11:117278620-117284002)	CEP164	Likely pathogenic	no assertion criteria provided
1349401	NM_014956.5(CEP164):c.2066+1G>A	CEP164	Likely pathogenic	criteria provided, single submitter
1352747	NM_014956.5(CEP164):c.2616+1G>A	CEP164	Likely pathogenic	criteria provided, single submitter
1481538	NM_014956.5(CEP164):c.765+1G>A	CEP164	Likely pathogenic	criteria provided, single submitter
1484586	NM_014956.5(CEP164):c.2284-1G>A	CEP164	Likely pathogenic	criteria provided, single submitter
1500630	NM_014956.5(CEP164):c.766-2A>G	CEP164	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CEP164	Definitive	Autosomal recessive	nephronophthisis 15	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP164	Orphanet:3156	Senior-Loken syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CEP164	HGNC:29182	ENSG00000110274	Q9UPV0	Centrosomal protein of 164 kDa	gencc,clinvar
BACE1	HGNC:933	ENSG00000186318	P56817	Beta-secretase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
BACE1	Beta-secretase 1	Responsible for the proteolytic processing of the amyloid precursor protein (APP).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP164	Scaffold/PPI	no		WW_dom, WW_dom_sf, MT-Golgi_org_protein
BACE1	Protease	yes	3.4.23.46	Aspartic_peptidase_A1, Aspartic_peptidase_AS, BACE

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ cell	1
sperm	1
tendon of biceps brachii	1
C1 segment of cervical spinal cord	1
body of pancreas	1
inferior vagus X ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP164	261	ubiquitous	marker	sperm, tendon of biceps brachii, male germ cell
BACE1	278	ubiquitous	marker	inferior vagus X ganglion, body of pancreas, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BACE1	2,883
CEP164	2,366

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BACE1	P56817	350
CEP164	Q9UPV0	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Centrosome maturation	1	126.9×	0.029	CEP164
Loss of Nlp from mitotic centrosomes	1	79.3×	0.029	CEP164
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.029	CEP164
AURKA Activation by TPX2	1	76.1×	0.029	CEP164
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.029	CEP164
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.029	CEP164
Mitotic G2-G2/M phases	1	63.4×	0.029	CEP164
G2/M Transition	1	63.4×	0.029	CEP164
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.029	CEP164
Anchoring of the basal body to the plasma membrane	1	56.5×	0.029	CEP164
Cilium Assembly	1	54.4×	0.029	CEP164
Amyloid fiber formation	1	51.4×	0.029	BACE1
Mitotic Prometaphase	1	34.6×	0.036	CEP164
Organelle biogenesis and maintenance	1	33.0×	0.036	CEP164
M Phase	1	33.0×	0.036	CEP164
Cell Cycle, Mitotic	1	24.1×	0.046	CEP164
Cell Cycle	1	18.0×	0.058	CEP164
Metabolism of proteins	1	6.2×	0.155	BACE1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
signaling receptor ligand precursor processing	1	2106.5×	0.004	BACE1
swimming behavior	1	1685.2×	0.004	BACE1
response to insulin-like growth factor stimulus	1	1404.3×	0.004	BACE1
cellular response to manganese ion	1	1203.7×	0.004	BACE1
amyloid-beta formation	1	936.2×	0.004	BACE1
amyloid-beta metabolic process	1	766.0×	0.004	BACE1
amyloid precursor protein catabolic process	1	601.9×	0.004	BACE1
detection of mechanical stimulus involved in sensory perception of pain	1	561.7×	0.004	BACE1
prepulse inhibition	1	561.7×	0.004	BACE1
response to lead ion	1	468.1×	0.004	BACE1
membrane protein ectodomain proteolysis	1	324.1×	0.005	BACE1
cellular response to copper ion	1	312.1×	0.005	BACE1
amyloid fibril formation	1	300.9×	0.005	BACE1
presynaptic modulation of chemical synaptic transmission	1	227.7×	0.007	BACE1
cellular response to amyloid-beta	1	195.9×	0.007	BACE1
positive regulation of neuron apoptotic process	1	135.9×	0.010	BACE1
protein processing	1	85.1×	0.014	BACE1
cilium assembly	1	36.8×	0.031	CEP164
DNA repair	1	31.9×	0.034	CEP164
cell division	1	23.1×	0.045	CEP164
proteolysis	1	17.1×	0.058	BACE1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
BACE1	CIANIDANOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BACE1	26	4
CEP164	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CIANIDANOL	4	BACE1
DONEPEZIL	4	BACE1
CHLOROQUINE	4	BACE1
GEFITINIB	4	BACE1
TYRAMINE	3	BACE1
CURCUMIN	3	BACE1
CAFFEIC ACID	3	BACE1
HYDROXYTYROSOL	3	BACE1
RUTIN	3	BACE1
EPIGALOCATECHIN GALLATE	3	BACE1
VERUBECESTAT	3	BACE1
LANABECESTAT	3	BACE1
ELENBECESTAT	3	BACE1
PHLOROGLUCINOL	3	BACE1
QUERCETIN	3	BACE1
(+)-EPICATECHIN	2	BACE1
SPICLOMAZINE	2	BACE1
LUTEOLIN	2	BACE1
ATABECESTAT	2	BACE1
ACETOSIDE	2	BACE1
(-)-EPICATECHIN	2	BACE1
ELLAGIC ACID	2	BACE1
KAEMPFEROL	1	BACE1
AZD-3839	1	BACE1
LY-2811376	1	BACE1
LY-2886721	1	BACE1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BACE1	1,237	Binding:1230, Functional:6, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BACE1	3.4.23.46	memapsin 2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BACE1	1,237

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

26 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)
CIANIDANOL	4	BACE1
DONEPEZIL	4	BACE1
CHLOROQUINE	4	BACE1
GEFITINIB	4	BACE1
TYRAMINE	3	BACE1
CURCUMIN	3	BACE1
CAFFEIC ACID	3	BACE1
HYDROXYTYROSOL	3	BACE1
RUTIN	3	BACE1
EPIGALOCATECHIN GALLATE	3	BACE1
VERUBECESTAT	3	BACE1
LANABECESTAT	3	BACE1
ELENBECESTAT	3	BACE1
PHLOROGLUCINOL	3	BACE1
QUERCETIN	3	BACE1
(+)-EPICATECHIN	2	BACE1
SPICLOMAZINE	2	BACE1
LUTEOLIN	2	BACE1
ATABECESTAT	2	BACE1
ACETOSIDE	2	BACE1
(-)-EPICATECHIN	2	BACE1
ELLAGIC ACID	2	BACE1
KAEMPFEROL	1	BACE1
AZD-3839	1	BACE1
LY-2811376	1	BACE1
LY-2886721	1	BACE1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BACE1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CEP164

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP164	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.