Senior-Loken syndrome 1

Summary

Senior-Loken syndrome 1 (MONDO:0009962) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 225

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Senior-Loken syndrome 1
Mondo ID	MONDO:0009962
OMIM	266900
DOID	DOID:0061277
SNOMED CT	236531005
UMLS	C4551559
MedGen	1639722
GARD	0024701
Is cancer (heuristic)	no

Also known as: NPHP1 Senior-Loken syndrome · Senior-Loken syndrome 1 · Senior-Loken syndrome caused by mutation in NPHP1 · Senior-Loken syndrome type 1 · senior-loken syndrome-1 · SLSN1

Data availability: 225 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Senior-Loken syndrome › Senior-Loken syndrome 1

Related subtypes (8): senior-loken syndrome 3, Senior-Loken syndrome 4, Senior-Loken syndrome 5, Senior-Loken syndrome 6, Senior-Loken syndrome 7, nephronophthisis 15, 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

225 retrieved; paginated sample, class counts are floors:

130 uncertain significance, 32 conflicting classifications of pathogenicity, 17 likely pathogenic, 13 pathogenic, 13 likely benign, 12 pathogenic/likely pathogenic, 5 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
56733	NM_025114.4(CEP290):c.1984C>T (p.Gln662Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
2158077	NM_000784.4(CYP27A1):c.646+1G>A	CYP27A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
237627	NM_000272.5(NPHP1):c.(?-45)(*443_?)del	LOC126806306	Pathogenic	criteria provided, multiple submitters, no conflicts
1030710	NM_001128178.3(NPHP1):c.1588C>T (p.Arg530Ter)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070446	NM_001128178.3(NPHP1):c.483del (p.Asp162fs)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179110	GRCh37/hg19 2q13(chr2:110880925-110962590)	NPHP1	Pathogenic	no assertion criteria provided
1179212	GRCh37/hg19 2q13(chr2:110880893-110962659)	NPHP1	Pathogenic	no assertion criteria provided
2171349	NM_001128178.3(NPHP1):c.771+58C>T	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203131	NM_001128178.3(NPHP1):c.84_87del (p.Ser29fs)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
2677270	NM_001128178.3(NPHP1):c.69+1del	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677274	NM_001128178.3(NPHP1):c.127C>T (p.Gln43Ter)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734257	NM_001128178.3(NPHP1):c.735del (p.His247fs)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
283524	NM_001128178.3(NPHP1):c.555dup (p.Pro186fs)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
286936	NM_001128178.3(NPHP1):c.329+1G>A	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3239950	NM_001128178.3(NPHP1):c.182del (p.Asn61fs)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3239952	NM_001128178.3(NPHP1):c.385_386del (p.Ser129fs)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382874	NM_001128178.3(NPHP1):c.349G>T (p.Glu117Ter)	NPHP1	Pathogenic	criteria provided, single submitter
3507	NM_001128178.3(NPHP1):c.1716+1G>T	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3510	NM_001128178.3(NPHP1):c.859G>A (p.Gly287Arg)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
3775520	NM_001128178.3(NPHP1):c.609dup (p.Arg204fs)	NPHP1	Pathogenic	criteria provided, single submitter
579607	NM_001128178.3(NPHP1):c.871C>T (p.Arg291Ter)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
595311	NM_001128178.3(NPHP1):c.415G>T (p.Glu139Ter)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
595558	NM_001128178.3(NPHP1):c.1551del (p.Ile517fs)	NPHP1	Pathogenic	criteria provided, multiple submitters, no conflicts
838041	NM_001128178.3(NPHP1):c.643G>T (p.Glu215Ter)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
854715	NM_001128178.3(NPHP1):c.1886G>A (p.Trp629Ter)	NPHP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584249	NM_001128178.3(NPHP1):c.1103_1104del (p.Thr368fs)	LOC126806306	Likely pathogenic	criteria provided, single submitter
1467632	NM_001128178.3(NPHP1):c.143+1G>C	NPHP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1503211	NM_001128178.3(NPHP1):c.729-2A>G	NPHP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2760352	NM_001128178.3(NPHP1):c.522+1G>A	NPHP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584231	NM_001128178.3(NPHP1):c.1893dup (p.Ile632fs)	NPHP1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP27A1	Orphanet:909	Cerebrotendinous xanthomatosis
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
NPHP1	Orphanet:110	Bardet-Biedl syndrome
NPHP1	Orphanet:220497	Joubert syndrome with renal defect
NPHP1	Orphanet:3156	Senior-Loken syndrome
NPHP1	Orphanet:93592	Juvenile nephronophthisis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP27A1	HGNC:2605	ENSG00000135929	Q02318	Sterol 26-hydroxylase, mitochondrial	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
NPHP1	HGNC:7905	ENSG00000144061	O15259	Nephrocystin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP27A1	Sterol 26-hydroxylase, mitochondrial	Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
NPHP1	Nephrocystin-1	Together with BCAR1 it may play a role in the control of epithelial cell polarity.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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	1	5.8×	0.345
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP27A1	Enzyme (other)	yes	1.14.15.15	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
NPHP1	Scaffold/PPI	no		SH3_domain, NPHP1_SH3, SH3-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	2
C1 segment of cervical spinal cord	1
liver	1
right lobe of liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
ventricular zone	1
bronchial epithelial cell	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP27A1	263	ubiquitous	marker	right lobe of liver, liver, C1 segment of cervical spinal cord
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
NPHP1	193	ubiquitous	marker	right uterine tube, bronchial epithelial cell, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
CYP27A1	2,351
NPHP1	2,302

Intra-cohort edges

A	B	Sources
CEP290	NPHP1	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NPHP1	O15259	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CYP27A1	Q02318	89.02
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP27A1 causes CTX	1	3806.7×	0.003	CYP27A1
Anchoring of the basal body to the plasma membrane	2	75.4×	0.003	CEP290, NPHP1
Synthesis of bile acids and bile salts via 24-hydroxycholesterol	1	292.8×	0.024	CYP27A1
Synthesis of bile acids and bile salts via 27-hydroxycholesterol	1	253.8×	0.024	CYP27A1
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	152.3×	0.030	CYP27A1
Endogenous sterols	1	131.3×	0.030	CYP27A1
Centrosome maturation	1	84.6×	0.040	CEP290
Loss of Nlp from mitotic centrosomes	1	52.9×	0.040	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	52.9×	0.040	CEP290
AURKA Activation by TPX2	1	50.8×	0.040	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	45.3×	0.040	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	42.3×	0.040	CEP290
Mitotic G2-G2/M phases	1	42.3×	0.040	CEP290
G2/M Transition	1	42.3×	0.040	CEP290
Recruitment of NuMA to mitotic centrosomes	1	38.8×	0.041	CEP290
Cilium Assembly	1	36.2×	0.041	CEP290
Mitotic Prometaphase	1	23.1×	0.057	CEP290
Organelle biogenesis and maintenance	1	22.0×	0.057	CEP290
M Phase	1	22.0×	0.057	CEP290
Cell Cycle, Mitotic	1	16.1×	0.073	CEP290
Cell Cycle	1	12.0×	0.093	CEP290
Innate Immune System	1	8.5×	0.123	CEP290
Neutrophil degranulation	1	7.7×	0.130	CEP290
Immune System	1	4.3×	0.214	CEP290

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete ciliary basal body-plasma membrane docking	1	2808.7×	0.004	CEP290
calcitriol biosynthetic process from calciol	1	1872.4×	0.004	CYP27A1
protein localization involved in establishment of planar polarity	1	1872.4×	0.004	NPHP1
ciliary transition zone assembly	1	1872.4×	0.004	CEP290
visual behavior	1	936.2×	0.005	NPHP1
pronephros development	1	802.5×	0.005	CEP290
regulation of establishment of protein localization	1	802.5×	0.005	CEP290
otic vesicle formation	1	702.2×	0.005	CEP290
cholesterol catabolic process	1	624.1×	0.005	CYP27A1
spermatid differentiation	1	561.7×	0.005	NPHP1
positive regulation of bicellular tight junction assembly	1	561.7×	0.005	NPHP1
hindbrain development	1	374.5×	0.006	CEP290
sterol metabolic process	1	280.9×	0.007	CYP27A1
eye photoreceptor cell development	1	280.9×	0.007	CEP290
positive regulation of intracellular protein transport	1	224.7×	0.008	CEP290
bile acid biosynthetic process	1	208.1×	0.008	CYP27A1
cell projection organization	1	124.8×	0.013	NPHP1
camera-type eye development	1	119.5×	0.013	CEP290
non-motile cilium assembly	1	96.8×	0.015	CEP290
retina development in camera-type eye	1	85.1×	0.016	NPHP1
cholesterol metabolic process	1	65.3×	0.020	CYP27A1
kidney development	1	46.8×	0.027	CEP290
cell-cell adhesion	1	33.8×	0.036	NPHP1
actin cytoskeleton organization	1	26.4×	0.044	NPHP1
cilium assembly	1	24.5×	0.045	CEP290
protein transport	1	14.6×	0.072	CEP290
positive regulation of DNA-templated transcription	1	9.3×	0.107	CEP290
signal transduction	1	5.3×	0.176	NPHP1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP27A1	0	0
CEP290	0	0
NPHP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CYP27A1	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP27A1	1.14.15.15, 1.14.99.38	cholestanetriol 26-monooxygenase, cholesterol 25-monooxygenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CYP27A1
E	Difficult family or no structure, no drug	2	CEP290, NPHP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CYP27A1	5	—
CEP290	0	—
NPHP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.