CEP290-related ciliopathy

disease
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Also known as amaurosis congenita of Leber, type 10Bardet-Biedl syndrome 14Bardet-Biedl syndrome type 14BBS14CEP290 ciliopathyCEP290 Joubert syndromeCEP290 Leber congenital amaurosisCEP290 Meckel syndromeCEP290 Senior-Loken syndromeJBTS5Joubert syndrome 5Joubert syndrome caused by mutation in CEP290Joubert syndrome type 5LCA10Leber congenital amaurosis 10Leber congenital amaurosis caused by mutation in CEP290Leber congenital amaurosis type 10Meckel syndrome 4Meckel syndrome caused by mutation in CEP290Meckel syndrome, type 4

Summary

CEP290-related ciliopathy (MONDO:0100451) is a disease (an umbrella term covering 5 Mondo subtypes) with 3 cohort genes and 6 clinical trials. Top therapeutic interventions include sepofarsen and brinretigene vesgedparvovec.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 3
  • ClinVar variants: 40
  • Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameCEP290-related ciliopathy
Mondo IDMONDO:0100451
GARD0026225
Is cancer (heuristic)no

Also known as: amaurosis congenita of Leber, type 10 · Bardet-Biedl syndrome 14 · Bardet-Biedl syndrome type 14 · BBS14 · CEP290 ciliopathy · CEP290 Joubert syndrome · CEP290 Leber congenital amaurosis · CEP290 Meckel syndrome · CEP290 Senior-Loken syndrome · JBTS5 · Joubert syndrome 5 · Joubert syndrome caused by mutation in CEP290 · Joubert syndrome type 5 · LCA10 · Leber congenital amaurosis 10 · Leber congenital amaurosis caused by mutation in CEP290 · Leber congenital amaurosis type 10 · Meckel syndrome 4 · Meckel syndrome caused by mutation in CEP290 · Meckel syndrome, type 4 (+8 more)

Data availability: 40 ClinVar variants.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary diseaseciliopathyCEP290-related ciliopathy

Related subtypes (35): Alstrom syndrome, Marden-Walker syndrome, nephronophthisis 1, Bardet-Biedl syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Jeune syndrome, Joubert syndrome, Meckel syndrome, retinal ciliopathy, oculocerebrodental syndrome, 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 (5): Joubert syndrome 5, Senior-Loken syndrome 6, Meckel syndrome, type 4, Leber congenital amaurosis 10, Bardet-Biedl syndrome 14

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

40 retrieved; paginated sample, class counts are floors:

16 pathogenic, 10 uncertain significance, 8 pathogenic/likely pathogenic, 5 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
1069579NM_025114.4(CEP290):c.5235_5238del (p.Ser1745fs)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1072859NM_025114.4(CEP290):c.3922C>T (p.Gln1308Ter)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
1074486NM_025114.4(CEP290):c.4983del (p.Lys1661_Val1662insTer)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1339NM_025114.4(CEP290):c.4723A>T (p.Lys1575Ter)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
1986597NM_025114.4(CEP290):c.1616del (p.Leu538_Leu539insTer)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
2114918NM_025114.4(CEP290):c.6838A>T (p.Lys2280Ter)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
217624NM_025114.4(CEP290):c.164_167del (p.Thr55fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
4081609NM_025114.4(CEP290):c.4544_4548del (p.Arg1515fs)CEP290Pathogeniccriteria provided, single submitter
497937NM_025114.4(CEP290):c.6798G>A (p.Trp2266Ter)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
522742NM_025114.4(CEP290):c.1419_1423del (p.Ile474fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
56729NM_025114.4(CEP290):c.1219_1220del (p.Met407fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
56734NM_025114.4(CEP290):c.289G>T (p.Glu97Ter)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
572652NM_025114.4(CEP290):c.4962_4963del (p.Glu1656fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
635087NM_025114.4(CEP290):c.4792_4795del (p.Lys1598fs)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
654872NM_025114.4(CEP290):c.6869del (p.Asn2290fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
654881NM_025114.4(CEP290):c.322C>T (p.Arg108Ter)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
665410NM_025114.4(CEP290):c.3802C>T (p.Gln1268Ter)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
830333NM_025114.4(CEP290):c.7341_7344dup (p.Ser2449fs)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
855145NM_025114.4(CEP290):c.6448_6455del (p.Gln2150fs)CEP290Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
857949NM_025114.4(CEP290):c.1189+1G>ACEP290Pathogeniccriteria provided, multiple submitters, no conflicts
930681NM_025114.4(CEP290):c.7027del (p.Val2343fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
99859NM_025114.4(CEP290):c.5515_5518del (p.Glu1839fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
99860NM_025114.4(CEP290):c.5649dup (p.Leu1884fs)CEP290Pathogeniccriteria provided, multiple submitters, no conflicts
856893NM_025114.4(CEP290):c.7328_7332del (p.Glu2443fs)RLIG1Pathogeniccriteria provided, multiple submitters, no conflicts
2574041NM_020944.3(GBA2):c.715dup (p.Tyr239fs)GBA2Likely pathogeniccriteria provided, single submitter
310628NM_025114.4(CEP290):c.503G>A (p.Arg168His)CEP290Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
3575347NM_025114.4(CEP290):c.7256del (p.Ser2419fs)CEP290Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
449448NM_025114.4(CEP290):c.4438-3delCEP290Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
695268NM_025114.4(CEP290):c.2090C>G (p.Ala697Gly)CEP290Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
697728NM_025114.4(CEP290):c.2638G>T (p.Ala880Ser)CEP290Conflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
GBA2Orphanet:320391Autosomal recessive spastic paraplegia type 46
GBA2Orphanet:352641Autosomal recessive cerebellar ataxia with late-onset spasticity
CEP290Orphanet:110Bardet-Biedl syndrome
CEP290Orphanet:2318Joubert syndrome with oculorenal defect
CEP290Orphanet:3156Senior-Loken syndrome
CEP290Orphanet:564Meckel syndrome
CEP290Orphanet:65Leber congenital amaurosis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
GBA2HGNC:18986ENSG00000070610Q9HCG7Non-lysosomal glucosylceramidaseclinvar
RLIG1HGNC:25322ENSG00000133641Q8N999RNA ligase 1clinvar
CEP290HGNC:29021ENSG00000198707O15078Centrosomal protein of 290 kDaclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
GBA2Non-lysosomal glucosylceramidaseNon-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine) to free glucose and ceramides (such as N-acylsphing-4-enine).
RLIG1RNA ligase 1Functions as an RNA ligase, in vitro.
CEP290Centrosomal protein of 290 kDaInvolved in early and late steps in cilia formation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · 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.

FamilyGenesFoldFDR
Enzyme (other)14.0×0.460
Other/Unknown21.2×0.587

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
GBA2Enzyme (other)yes3.2.1.45GH116_catalytic, 6-hairpin_glycosidase_sf, 6hp_glycosidase-like_sf
RLIG1Other/UnknownnoRLIG1
CEP290Other/UnknownnoCep290, Cep209_CC5

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)3
unknown0

Top tissues across cohort

TissueCohort genes
metanephros cortex1
right hemisphere of cerebellum1
small intestine Peyer’s patch1
Brodmann (1909) area 231
endothelial cell1
oocyte1
male germ line stem cell (sensu Vertebrata) in testis1
right uterine tube1
ventricular zone1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
GBA2248ubiquitousmarkermetanephros cortex, right hemisphere of cerebellum, small intestine Peyer’s patch
RLIG1288ubiquitousmarkerendothelial cell, Brodmann (1909) area 23, oocyte
CEP290278ubiquitousmarkerright uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CEP2902,778
GBA21,709
RLIG1506

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
RLIG1Q8N99992.03
GBA2Q9HCG789.77
CEP290O1507860.90

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.

PathwayCohort genesFoldFDRSample cohort genes
Glycosphingolipid catabolism1146.4×0.031GBA2
Centrosome maturation1126.9×0.031CEP290
Loss of Nlp from mitotic centrosomes179.3×0.031CEP290
Loss of proteins required for interphase microtubule organization from the centrosome179.3×0.031CEP290
AURKA Activation by TPX2176.1×0.031CEP290
Recruitment of mitotic centrosome proteins and complexes168.0×0.031CEP290
Regulation of PLK1 Activity at G2/M Transition163.4×0.031CEP290
Mitotic G2-G2/M phases163.4×0.031CEP290
G2/M Transition163.4×0.031CEP290
Recruitment of NuMA to mitotic centrosomes158.3×0.031CEP290
Anchoring of the basal body to the plasma membrane156.5×0.031CEP290
Cilium Assembly154.4×0.031CEP290
Mitotic Prometaphase134.6×0.040CEP290
Organelle biogenesis and maintenance133.0×0.040CEP290
M Phase133.0×0.040CEP290
Cell Cycle, Mitotic124.1×0.051CEP290
Cell Cycle118.0×0.064CEP290
Innate Immune System112.8×0.085CEP290
Neutrophil degranulation111.5×0.089CEP290
Immune System16.5×0.148CEP290

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 termCohort genesFoldFDRSample cohort genes
obsolete ciliary basal body-plasma membrane docking12808.7×0.004CEP290
glucosylceramide catabolic process11872.4×0.004GBA2
RNA repair11872.4×0.004RLIG1
ciliary transition zone assembly11872.4×0.004CEP290
glycoside catabolic process1936.2×0.005GBA2
regulation of membrane lipid distribution1936.2×0.005GBA2
pronephros development1802.5×0.005CEP290
regulation of establishment of protein localization1802.5×0.005CEP290
otic vesicle formation1702.2×0.005CEP290
glycosphingolipid catabolic process1510.7×0.006GBA2
glycolipid biosynthetic process1468.1×0.006GBA2
hindbrain development1374.5×0.006CEP290
regulation of microtubule polymerization1374.5×0.006GBA2
response to reactive oxygen species1351.1×0.006RLIG1
bile acid metabolic process1330.4×0.006GBA2
eye photoreceptor cell development1280.9×0.006CEP290
central nervous system neuron development1267.5×0.006GBA2
positive regulation of intracellular protein transport1224.7×0.007CEP290
regulation of actin filament polymerization1193.7×0.008GBA2
camera-type eye development1119.5×0.012CEP290
non-motile cilium assembly196.8×0.014CEP290
hematopoietic progenitor cell differentiation179.1×0.017RLIG1
cholesterol metabolic process165.3×0.019GBA2
kidney development146.8×0.025CEP290
carbohydrate metabolic process145.3×0.025GBA2
central nervous system development138.5×0.029GBA2
cilium assembly124.5×0.043CEP290
protein transport114.6×0.069CEP290
positive regulation of DNA-templated transcription19.3×0.104CEP290

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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.

SymbolExample approved molecule
GBA2MIGLUSTAT

Top cohort targets by molecule count

SymbolMoleculesMax phase
GBA264
RLIG100
CEP29000

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MIGLUSTAT4GBA2
MIGALASTAT4GBA2
LUCERASTAT3GBA2
AFEGOSTAT2GBA2
DUVOGLUSTAT2GBA2
NIZUBAGLUSTAT2GBA2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
GBA238Binding:38

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
GBA23.2.1.45glucosylceramidase

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

6 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.

CompoundMax phaseCohort target (bioactivity)
MIGLUSTAT4GBA2
MIGALASTAT4GBA2
LUCERASTAT3GBA2
AFEGOSTAT2GBA2
DUVOGLUSTAT2GBA2
NIZUBAGLUSTAT2GBA2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1GBA2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug2RLIG1, CEP290

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
RLIG10
CEP2900

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE2/PHASE32
PHASE1/PHASE22
PHASE31
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03913143PHASE2/PHASE3ACTIVE_NOT_RECRUITINGA Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT06891443PHASE3RECRUITINGStudy to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT04855045PHASE2/PHASE3UNKNOWNAn Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479PHASE1/PHASE2UNKNOWNSingle Ascending Dose Study in Participants With LCA10
NCT03913130PHASE1/PHASE2TERMINATEDExtension Study to Study PQ-110-001 (NCT03140969)
NCT03396042Not specifiedCOMPLETEDNatural History Study of CEP290-Related Retinal Degeneration

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
SEPOFARSEN24
BRINRETIGENE VESGEDPARVOVEC21