Senior-Loken syndrome

Summary

Senior-Loken syndrome (MONDO:0017842) is a disease (an umbrella term covering 9 Mondo subtypes) caused by NPHP3 (GenCC Definitive), with 13 cohort genes and 1 clinical trial. The dominant Reactome pathway is Anchoring of the basal body to the plasma membrane (7 cohort genes).

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: NPHP3 (GenCC Definitive)
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 13
• ClinVar variants: 12
• Phenotypes (HPO): 16
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000505	Visual impairment	Very frequent (80-99%)
HP:0000556	Retinal dystrophy	Very frequent (80-99%)
HP:0000822	Hypertension	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0003774	Stage 5 chronic kidney disease	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0007703	Abnormality of retinal pigmentation	Very frequent (80-99%)
HP:0012622	Chronic kidney disease	Very frequent (80-99%)
HP:0000090	Nephronophthisis	Frequent (30-79%)
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0008209	Premature ovarian insufficiency	Frequent (30-79%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0002612	Congenital hepatic fibrosis	Occasional (5-29%)
HP:0004348	Abnormality of bone mineral density	Occasional (5-29%)
HP:0010579	Cone-shaped epiphysis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Senior-Loken syndrome
Mondo ID	MONDO:0017842
MeSH	C537580
OMIM	266900
Orphanet	3156
DOID	DOID:0050576
ICD-11	1975732692
NCIT	C168588
UMLS	C0403553
MedGen	96045
GARD	0000322
Is cancer (heuristic)	no

Also known as: nephronophthisis with retinal dystrophy · renal dysplasia retinal aplasia · renal dysplasia-retinal aplasia syndrome · Senior Loken syndrome · SLSN

Data availability: 12 ClinVar variants · 12 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

Related subtypes (35): Alstrom syndrome, Marden-Walker syndrome, nephronophthisis 1, Bardet-Biedl syndrome, primary ciliary dyskinesia, Jeune syndrome, Joubert syndrome, Meckel syndrome, retinal ciliopathy, oculocerebrodental syndrome, CEP290-related ciliopathy, IFT140-related recessive ciliopathy, BBS9-related ciliopathy, BBS10-related ciliopathy, CEP164-related ciliopathy, CFAP418-related ciliopathy, WDPCP-related ciliopathy, SDCCAG8-related ciliopathy, KIF7-related ciliopathy, Alsahan-Harris syndrome, OFD1-related ciliopathy, BBS7-related ciliopathy, BBS1-related ciliopathy, BBS4-related ciliopathy, BBS12-related ciliopathy, LZTFL1-related ciliopathy, BBS5-related ciliopathy, BBS2-related ciliopathy, TTC8-related ciliopathy, MKKS-related ciliopathy, ARL6-related ciliopathy, MKS1-related ciliopathy, TUBB4B-related ciliopathy, INTU-related skeletal ciliopathy, ciliopathy-IFT74

Subtypes (9): Senior-Loken syndrome 1, 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

12 retrieved; paginated sample, class counts are floors:

5 pathogenic/likely pathogenic, 4 pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071036	NM_025114.4(CEP290):c.3708dup (p.Arg1237fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1830	NM_001023570.4(IQCB1):c.1381C>T (p.Arg461Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
504877	NM_001023570.4(IQCB1):c.1363C>T (p.Arg455Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
812337	NM_001023570.4(IQCB1):c.1108dup (p.Met370fs)	IQCB1	Pathogenic	no assertion criteria provided
812430	NM_006642.5(SDCCAG8):c.1714C>T (p.Gln572Ter)	SDCCAG8	Pathogenic	no assertion criteria provided
30935	NM_024753.5(TTC21B):c.626C>T (p.Pro209Leu)	TTC21B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449860	NM_024753.5(TTC21B):c.1088-1G>C	TTC21B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1473602	NM_025132.4(WDR19):c.3184-2A>C	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30703	NM_025132.4(WDR19):c.2129T>C (p.Leu710Ser)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1949159	NM_014956.5(CEP164):c.687+1G>A	CEP164	Likely pathogenic	criteria provided, multiple submitters, no conflicts
497880	NM_015102.5(NPHP4):c.1440G>A (p.Ser480=)	NPHP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
580774	NM_153240.5(NPHP3):c.3499C>T (p.Arg1167Cys)	NPHP3-ACAD11	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 83 · Orphanet: 32 · 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
IFT54	Definitive	Autosomal recessive	Senior-Loken syndrome 9	5
IQCB1	Definitive	Autosomal recessive	Senior-Loken syndrome 5	5
NPHP3	Definitive	Autosomal recessive	Senior-Loken syndrome	10
NPHP4	Definitive	Autosomal recessive	Senior-Loken syndrome 4	9
SDCCAG8	Definitive	Autosomal recessive	Senior-Loken syndrome 7	9
WDR19	Strong	Autosomal recessive	Senior-Loken syndrome 8	12
CEP164	Supportive	Autosomal recessive	Senior-Loken syndrome	5
CEP290	Supportive	Autosomal recessive	Senior-Loken syndrome	10
INVS	Supportive	Autosomal recessive	Senior-Loken syndrome	5
NPHP1	Supportive	Autosomal recessive	Senior-Loken syndrome	9
SCLT1	Limited	Autosomal recessive	Senior-Loken syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDCCAG8	Orphanet:110	Bardet-Biedl syndrome
SDCCAG8	Orphanet:3156	Senior-Loken syndrome
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
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
CEP164	Orphanet:3156	Senior-Loken syndrome
IFT54	Orphanet:3156	Senior-Loken syndrome
IFT54	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
INVS	Orphanet:3156	Senior-Loken syndrome
INVS	Orphanet:93591	Infantile nephronophthisis
SCLT1	Orphanet:110	Bardet-Biedl syndrome
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
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
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis

Cohort genes → proteins

13 cohort genes, 12 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDCCAG8	HGNC:10671	ENSG00000054282	Q86SQ7	Serologically defined colon cancer antigen 8	gencc,clinvar
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	gencc,clinvar
NPHP4	HGNC:19104	ENSG00000131697	O75161	Nephrocystin-4	gencc,clinvar
IQCB1	HGNC:28949	ENSG00000173226	Q15051	IQ calmodulin-binding motif-containing protein 1	gencc,clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	gencc,clinvar
CEP164	HGNC:29182	ENSG00000110274	Q9UPV0	Centrosomal protein of 164 kDa	gencc,clinvar
IFT54	HGNC:17861	ENSG00000204104	Q8TDR0	TRAF3-interacting protein 1	gencc
INVS	HGNC:17870	ENSG00000119509	Q9Y283	Inversin	gencc
SCLT1	HGNC:26406	ENSG00000151466	Q96NL6	Sodium channel and clathrin linker 1	gencc
NPHP1	HGNC:7905	ENSG00000144061	O15259	Nephrocystin-1	gencc
NPHP3	HGNC:7907	ENSG00000113971	Q7Z494	Nephrocystin-3	gencc
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	clinvar
NPHP3-ACAD11	HGNC:48351	ENSG00000274810		NPHP3-ACAD11 readthrough (NMD candidate)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDCCAG8	Serologically defined colon cancer antigen 8	Plays a role in the establishment of cell polarity and epithelial lumen formation.
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.
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.
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.
IFT54	TRAF3-interacting protein 1	Plays an inhibitory role on IL13 signaling by binding to IL13RA1.
INVS	Inversin	Required for normal renal development and establishment of left-right axis.
SCLT1	Sodium channel and clathrin linker 1	Adapter protein that links SCN10A to clathrin.
NPHP1	Nephrocystin-1	Together with BCAR1 it may play a role in the control of epithelial cell polarity.
NPHP3	Nephrocystin-3	Required for normal ciliary development and function.
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).

Protein-family classification

Druggable: 0 · Difficult: 4 · Unknown: 9 · Druggable fraction: 0.0

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	3	4.0×	0.107
Other/Unknown	9	1.2×	0.370
Transcription factor	1	0.6×	0.813

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDCCAG8	Other/Unknown	no		SDCCAG8
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
IQCB1	Other/Unknown	no		IQ_motif_EF-hand-BS, ARM-type_fold, P-loop_NTPase
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
CEP164	Scaffold/PPI	no		WW_dom, WW_dom_sf, MT-Golgi_org_protein
IFT54	Other/Unknown	no		TRAF3IP1, TRAF3IP1_N, TRAF3IP1_C
INVS	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Ankyrin_rpt, Ankyrin_rpt-contain_sf
SCLT1	Other/Unknown	no		SCLT1
NPHP1	Scaffold/PPI	no		SH3_domain, NPHP1_SH3, SH3-like_dom_sf
NPHP3	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, P-loop_NTPase
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
NPHP3-ACAD11	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

11 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	5
calcaneal tendon	4
bronchial epithelial cell	3
adenohypophysis	2
oocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
sural nerve	2
corpus callosum	1
thyroid gland	1
right lobe of thyroid gland	1
epithelium of nasopharynx	1
nasopharynx	1
ventricular zone	1
male germ cell	1
sperm	1
tendon of biceps brachii	1
adrenal tissue	1
buccal mucosa cell	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDCCAG8	134	ubiquitous	marker	corpus callosum, calcaneal tendon, thyroid gland
WDR19	269	ubiquitous	marker	right uterine tube, bronchial epithelial cell, adenohypophysis
NPHP4	165	ubiquitous	marker	right uterine tube, adenohypophysis, right lobe of thyroid gland
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
CEP164	261	ubiquitous	marker	sperm, tendon of biceps brachii, male germ cell
IFT54	265	ubiquitous	marker	oocyte, bronchial epithelial cell, sural nerve
INVS	215	ubiquitous	yes	calcaneal tendon, adrenal tissue, sural nerve
SCLT1	217	ubiquitous	marker	buccal mucosa cell, monocyte, leukocyte
NPHP1	193	ubiquitous	marker	right uterine tube, bronchial epithelial cell, olfactory segment of nasal mucosa
NPHP3	254	ubiquitous	marker	superficial temporal artery, layer of synovial tissue, left ovary
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
NPHP3-ACAD11	133	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, endometrium

Protein interactions among cohort

Intra-cohort edges: 25.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IQCB1	3,562
CEP290	2,778
CEP164	2,366
NPHP1	2,302
NPHP3	2,275
INVS	2,099
SDCCAG8	1,837
TTC21B	1,588
NPHP4	1,579
SCLT1	1,478

Intra-cohort edges

A	B	Sources
CEP164	CEP290	string_interaction
CEP164	INVS	biogrid_interaction
CEP164	NPHP3	intact
CEP164	SCLT1	string_interaction
CEP290	INVS	string_interaction
CEP290	IQCB1	biogrid_interaction, intact, string_interaction
CEP290	NPHP1	string_interaction
CEP290	NPHP3	string_interaction
CEP290	NPHP4	string_interaction
CEP290	SDCCAG8	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
IQCB1	SDCCAG8	string_interaction
NPHP1	NPHP3	biogrid_interaction, string_interaction
NPHP1	NPHP4	biogrid_interaction, intact, string_interaction
NPHP1	SDCCAG8	string_interaction
NPHP3	NPHP4	string_interaction
NPHP3	SDCCAG8	string_interaction
NPHP4	SDCCAG8	string_interaction
TTC21B	WDR19	biogrid_interaction, intact, string_interaction

Structural data

PDB: 6 · AlphaFold-only: 6 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR19	Q8NEZ3	4
CEP164	Q9UPV0	4
TTC21B	Q7Z4L5	3
IFT54	Q8TDR0	2
NPHP1	O15259	2
NPHP3	Q7Z494	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IQCB1	Q15051	83.05
SCLT1	Q96NL6	82.44
SDCCAG8	Q86SQ7	78.67
NPHP4	O75161	72.44
INVS	Q9Y283	70.76
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 13 evidence-associated genes (11 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 11 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	7	72.0×	3e-11	SDCCAG8, NPHP4, IQCB1, CEP290, CEP164, SCLT1, NPHP1
Cilium Assembly	6	59.3×	3e-09	SDCCAG8, IQCB1, CEP290, CEP164, IFT54, SCLT1
Organelle biogenesis and maintenance	6	36.0×	4e-08	SDCCAG8, IQCB1, CEP290, CEP164, IFT54, SCLT1
Centrosome maturation	3	69.2×	5e-05	SDCCAG8, CEP290, CEP164
Intraflagellar transport	3	54.6×	9e-05	WDR19, IFT54, TTC21B
Loss of Nlp from mitotic centrosomes	3	43.3×	1e-04	SDCCAG8, CEP290, CEP164
Loss of proteins required for interphase microtubule organization from the centrosome	3	43.3×	1e-04	SDCCAG8, CEP290, CEP164
AURKA Activation by TPX2	3	41.5×	1e-04	SDCCAG8, CEP290, CEP164
Recruitment of mitotic centrosome proteins and complexes	3	37.1×	1e-04	SDCCAG8, CEP290, CEP164
Regulation of PLK1 Activity at G2/M Transition	3	34.6×	1e-04	SDCCAG8, CEP290, CEP164
Mitotic G2-G2/M phases	3	34.6×	1e-04	SDCCAG8, CEP290, CEP164
G2/M Transition	3	34.6×	1e-04	SDCCAG8, CEP290, CEP164
Recruitment of NuMA to mitotic centrosomes	3	31.8×	2e-04	SDCCAG8, CEP290, CEP164
Mitotic Prometaphase	3	18.9×	7e-04	SDCCAG8, CEP290, CEP164
M Phase	3	18.0×	8e-04	SDCCAG8, CEP290, CEP164
Cell Cycle, Mitotic	3	13.1×	0.002	SDCCAG8, CEP290, CEP164
Hedgehog ‘off’ state	2	32.4×	0.002	WDR19, TTC21B
Cell Cycle	3	9.8×	0.004	SDCCAG8, CEP290, CEP164
Trafficking of myristoylated proteins to the cilium	1	207.6×	0.006	NPHP3
Signaling by Hippo	1	49.4×	0.023	NPHP4
Innate Immune System	1	2.3×	0.390	CEP290
Neutrophil degranulation	1	2.1×	0.403	CEP290
Immune System	1	1.2×	0.587	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 12 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	8	49.1×	5e-11	WDR19, IQCB1, CEP290, CEP164, IFT54, TTC21B, SCLT1, NPHP3
kidney development	4	46.8×	6e-05	CEP290, IFT54, INVS, NPHP3
maintenance of animal organ identity	2	561.7×	1e-04	IQCB1, NPHP3
photoreceptor cell maintenance	3	89.6×	1e-04	NPHP4, IQCB1, NPHP3
visual behavior	2	468.1×	1e-04	NPHP4, NPHP1
positive regulation of bicellular tight junction assembly	2	280.9×	4e-04	NPHP4, NPHP1
embryonic camera-type eye development	2	200.6×	6e-04	WDR19, IFT54
intraciliary retrograde transport	2	187.2×	6e-04	WDR19, TTC21B
negative regulation of canonical Wnt signaling pathway	3	29.5×	0.001	NPHP4, INVS, NPHP3
cell projection organization	2	62.4×	0.005	SDCCAG8, NPHP1
determination of intestine left/right asymmetry	1	1404.3×	0.005	NPHP3
determination of stomach left/right asymmetry	1	1404.3×	0.005	NPHP3
protein localization to ciliary inversin compartment	1	1404.3×	0.005	INVS
non-motile cilium assembly	2	48.4×	0.005	CEP290, NPHP3
retina development in camera-type eye	2	42.6×	0.007	NPHP4, NPHP1
convergent extension involved in gastrulation	1	702.2×	0.008	NPHP3
obsolete ciliary basal body-plasma membrane docking	1	702.2×	0.008	CEP290
regulation of intraciliary retrograde transport	1	702.2×	0.008	TTC21B
convergent extension	1	468.1×	0.010	NPHP3
protein localization involved in establishment of planar polarity	1	468.1×	0.010	NPHP1
ciliary transition zone assembly	1	468.1×	0.010	CEP290
morphogenesis of a polarized epithelium	1	351.1×	0.011	IFT54
ear morphogenesis	1	351.1×	0.011	WDR19
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	1	351.1×	0.011	WDR19
myotome development	1	351.1×	0.011	WDR19
protein localization to non-motile cilium	1	351.1×	0.011	TTC21B
determination of pancreatic left/right asymmetry	1	280.9×	0.012	NPHP3
digestive system development	1	280.9×	0.012	WDR19
cytosolic ciliogenesis	1	280.9×	0.012	IQCB1
protein localization to ciliary membrane	1	280.9×	0.012	WDR19

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 13

Druggability breadth: 0 of 13 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SDCCAG8	0	0
WDR19	0	0
NPHP4	0	0
IQCB1	0	0
CEP290	0	0
CEP164	0	0
IFT54	0	0
INVS	0	0
SCLT1	0	0
NPHP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; 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	0
E	Difficult family or no structure, no drug	13	SDCCAG8, WDR19, NPHP4, IQCB1, CEP290, CEP164, IFT54, INVS, SCLT1, NPHP1 (+3 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SDCCAG8	0	—
WDR19	0	—
NPHP4	0	—
IQCB1	0	—
CEP290	0	—
CEP164	0	—
IFT54	0	—
INVS	0	—
SCLT1	0	—
NPHP1	0	—
NPHP3	0	—
TTC21B	0	—
NPHP3-ACAD11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)