Senior-Loken syndrome 6

Summary

Senior-Loken syndrome 6 (MONDO:0012433) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 797

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Senior-Loken syndrome 6
Mondo ID	MONDO:0012433
MeSH	C565708
OMIM	610189
DOID	DOID:0061280
UMLS	C1857779
MedGen	387907
GARD	0015476
Is cancer (heuristic)	no

Also known as: CEP290 Senior-Loken syndrome · Senior-Loken syndrome 6 · Senior-Loken syndrome caused by mutation in CEP290 · Senior-Loken syndrome type 6 · SLSN6

Data availability: 797 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 6

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

600 retrieved; paginated sample, class counts are floors:

316 uncertain significance, 76 conflicting classifications of pathogenicity, 63 pathogenic/likely pathogenic, 63 likely pathogenic, 34 likely benign, 31 pathogenic, 9 benign, 8 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
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
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
1073200	NM_025114.4(CEP290):c.1060C>T (p.Gln354Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074481	NM_025114.4(CEP290):c.1258dup (p.Thr420fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074486	NM_025114.4(CEP290):c.4983del (p.Lys1661_Val1662insTer)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074543	NM_025114.4(CEP290):c.5788_5792del (p.Lys1930fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074952	NM_025114.4(CEP290):c.2213del (p.Asn737_Leu738insTer)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075280	NM_025114.4(CEP290):c.583_584del (p.Leu195fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075391	NM_025114.4(CEP290):c.5941G>T (p.Glu1981Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075924	NM_025114.4(CEP290):c.7282_7283dup (p.Tyr2429fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1185813	NM_025114.4(CEP290):c.712G>T (p.Glu238Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
126260	NM_025114.4(CEP290):c.4621del (p.Thr1541fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333	NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1336	NM_025114.4(CEP290):c.2218_2222del (p.Ile740fs)	CEP290	Pathogenic	no assertion criteria provided
1337	NM_025114.4(CEP290):c.2991+1655A>G	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339	NM_025114.4(CEP290):c.4723A>T (p.Lys1575Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1339724	NM_025114.4(CEP290):c.7198C>T (p.Gln2400Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342	NM_025114.4(CEP290):c.613C>T (p.Arg205Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1367157	NM_025114.4(CEP290):c.254dup (p.Asn85fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381343	NM_025114.4(CEP290):c.4737del (p.Asp1580fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1385952	NM_025114.4(CEP290):c.3240T>A (p.Tyr1080Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1387697	NM_025114.4(CEP290):c.7263dup (p.Glu2422Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1400998	NM_025114.4(CEP290):c.1750del (p.Ser584fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1405608	NM_025114.4(CEP290):c.3285del (p.Phe1095fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1417087	NM_025114.4(CEP290):c.584del (p.Leu195fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1447314	NM_025114.4(CEP290):c.4677T>G (p.Tyr1559Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
DDHD2	Orphanet:320380	Autosomal recessive spastic paraplegia type 54

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
RLIG1	HGNC:25322	ENSG00000133641	Q8N999	RNA ligase 1	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
DDHD2	HGNC:29106	ENSG00000085788	O94830	Triacylglycerol hydrolase DDHD2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RLIG1	RNA ligase 1	Functions as an RNA ligase, in vitro.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
DDHD2	Triacylglycerol hydrolase DDHD2	Diacylglycerol (DAG) and triacylglycerol (TAG) lipase required for proper lipid homeostasis in the central nervous system.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RLIG1	Other/Unknown	no		RLIG1
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
DDHD2	Other/Unknown	no		SAM, WWE_dom, DDHD_dom

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
Brodmann (1909) area 23	2
endothelial cell	2
oocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
ventricular zone	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RLIG1	288	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, oocyte
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
DDHD2	294	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
DDHD2	1,153
RLIG1	506

Structural data

PDB: 0 · AlphaFold-only: 3 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RLIG1	Q8N999	92.03
DDHD2	O94830	74.70
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 3 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
Synthesis of PA	1	146.4×	0.031	DDHD2
Centrosome maturation	1	126.9×	0.031	CEP290
Loss of Nlp from mitotic centrosomes	1	79.3×	0.031	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.031	CEP290
AURKA Activation by TPX2	1	76.1×	0.031	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.031	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.031	CEP290
Mitotic G2-G2/M phases	1	63.4×	0.031	CEP290
G2/M Transition	1	63.4×	0.031	CEP290
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.031	CEP290
Anchoring of the basal body to the plasma membrane	1	56.5×	0.031	CEP290
Cilium Assembly	1	54.4×	0.031	CEP290
Mitotic Prometaphase	1	34.6×	0.040	CEP290
Organelle biogenesis and maintenance	1	33.0×	0.040	CEP290
M Phase	1	33.0×	0.040	CEP290
Cell Cycle, Mitotic	1	24.1×	0.051	CEP290
Cell Cycle	1	18.0×	0.064	CEP290
Innate Immune System	1	12.8×	0.085	CEP290
Neutrophil degranulation	1	11.5×	0.089	CEP290
Immune System	1	6.5×	0.148	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
RNA repair	1	1872.4×	0.004	RLIG1
ciliary transition zone assembly	1	1872.4×	0.004	CEP290
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
hindbrain development	1	374.5×	0.007	CEP290
mitochondrial fission	1	351.1×	0.007	DDHD2
response to reactive oxygen species	1	351.1×	0.007	RLIG1
lipid droplet organization	1	312.1×	0.007	DDHD2
eye photoreceptor cell development	1	280.9×	0.007	CEP290
triglyceride catabolic process	1	267.5×	0.007	DDHD2
positive regulation of mitochondrial fission	1	255.3×	0.007	DDHD2
positive regulation of intracellular protein transport	1	224.7×	0.007	CEP290
camera-type eye development	1	119.5×	0.013	CEP290
visual learning	1	102.1×	0.014	DDHD2
non-motile cilium assembly	1	96.8×	0.014	CEP290
hematopoietic progenitor cell differentiation	1	79.1×	0.016	RLIG1
locomotory behavior	1	59.8×	0.020	DDHD2
kidney development	1	46.8×	0.024	CEP290
cilium assembly	1	24.5×	0.044	CEP290
protein transport	1	14.6×	0.070	CEP290
positive regulation of DNA-templated transcription	1	9.3×	0.104	CEP290

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
RLIG1	0	0
CEP290	0	0
DDHD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DDHD2	2	Functional:2

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	0
E	Difficult family or no structure, no drug	3	RLIG1, CEP290, DDHD2

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)
RLIG1	0	—
CEP290	0	—
DDHD2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.