Joubert syndrome 5

Summary

Joubert syndrome 5 (MONDO:0012432) is a disease caused by CEP290 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CEP290 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 843

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 5
Mondo ID	MONDO:0012432
MeSH	C537688
OMIM	610188
DOID	DOID:0111000
UMLS	C1857780
MedGen	347545
GARD	0015475
Is cancer (heuristic)	no

Also known as: CEP290 Joubert syndrome · JBTS5 · Joubert syndrome 5 · Joubert syndrome caused by mutation in CEP290 · Joubert syndrome type 5

Data availability: 843 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome with oculorenal defect › Joubert syndrome 5

Related subtypes (4): Joubert syndrome 2, Joubert syndrome 9, Joubert syndrome 14, Joubert syndrome 16

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:

310 uncertain significance, 73 conflicting classifications of pathogenicity, 66 pathogenic/likely pathogenic, 63 likely pathogenic, 38 pathogenic, 33 likely benign, 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
1071036	NM_025114.4(CEP290):c.3708dup (p.Arg1237fs)	CEP290	Pathogenic/Likely 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
1335	NM_025114.4(CEP290):c.21G>T (p.Trp7Cys)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
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
1345	NM_025114.4(CEP290):c.5704G>T (p.Glu1902Ter)	CEP290	Pathogenic/Likely 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

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · 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
CEP290	Definitive	Autosomal recessive	Joubert syndrome 5	10

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

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
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	gencc,clinvar
RLIG1	HGNC:25322	ENSG00000133641	Q8N999	RNA ligase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
RLIG1	RNA ligase 1	Functions as an RNA ligase, in vitro.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

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

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 line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
ventricular zone	1
Brodmann (1909) area 23	1
endothelial cell	1
oocyte	1

Per-gene tissue summary (top 30)

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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
RLIG1	506

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RLIG1	Q8N999	92.03
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (1 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 1 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	253.8×	0.016	CEP290
Loss of Nlp from mitotic centrosomes	1	158.6×	0.016	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.016	CEP290
AURKA Activation by TPX2	1	152.3×	0.016	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.016	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.016	CEP290
Mitotic G2-G2/M phases	1	126.9×	0.016	CEP290
G2/M Transition	1	126.9×	0.016	CEP290
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.016	CEP290
Anchoring of the basal body to the plasma membrane	1	113.1×	0.016	CEP290
Cilium Assembly	1	108.8×	0.016	CEP290
Mitotic Prometaphase	1	69.2×	0.021	CEP290
Organelle biogenesis and maintenance	1	66.0×	0.021	CEP290
M Phase	1	66.0×	0.021	CEP290
Cell Cycle, Mitotic	1	48.2×	0.026	CEP290
Cell Cycle	1	36.0×	0.033	CEP290
Innate Immune System	1	25.5×	0.044	CEP290
Neutrophil degranulation	1	23.1×	0.046	CEP290
Immune System	1	13.0×	0.077	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 2 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	4213.0×	0.002	CEP290
RNA repair	1	2808.7×	0.002	RLIG1
ciliary transition zone assembly	1	2808.7×	0.002	CEP290
pronephros development	1	1203.7×	0.003	CEP290
regulation of establishment of protein localization	1	1203.7×	0.003	CEP290
otic vesicle formation	1	1053.2×	0.003	CEP290
hindbrain development	1	561.7×	0.004	CEP290
response to reactive oxygen species	1	526.6×	0.004	RLIG1
eye photoreceptor cell development	1	421.3×	0.004	CEP290
positive regulation of intracellular protein transport	1	337.0×	0.005	CEP290
camera-type eye development	1	179.3×	0.009	CEP290
non-motile cilium assembly	1	145.3×	0.010	CEP290
hematopoietic progenitor cell differentiation	1	118.7×	0.011	RLIG1
kidney development	1	70.2×	0.017	CEP290
cilium assembly	1	36.8×	0.031	CEP290
protein transport	1	21.9×	0.048	CEP290
positive regulation of DNA-templated transcription	1	14.0×	0.070	CEP290

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
CEP290	0	0
RLIG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	2	CEP290, RLIG1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP290	0	—
RLIG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.