Joubert syndrome 15

Summary

Joubert syndrome 15 (MONDO:0013763) is a disease caused by CEP41 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CEP41 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 393

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 15
Mondo ID	MONDO:0013763
OMIM	614464
DOID	DOID:0110984
UMLS	C3280897
MedGen	482527
GARD	0015806
Is cancer (heuristic)	no

Also known as: CEP41 Joubert syndrome · JBTS15 · Joubert syndrome 15 · Joubert syndrome caused by mutation in CEP41 · Joubert syndrome type 15

Data availability: 393 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 ocular defect › Joubert syndrome 15

Related subtypes (4): Joubert syndrome 3, Joubert syndrome 14, Joubert syndrome 20, Joubert syndrome 28

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

393 retrieved; paginated sample, class counts are floors:

219 uncertain significance, 118 likely benign, 18 benign, 15 conflicting classifications of pathogenicity, 14 pathogenic, 5 likely pathogenic, 3 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029717	NM_018718.3(CEP41):c.34-2A>G	CEP41	Pathogenic	criteria provided, single submitter
1457092	NM_018718.3(CEP41):c.7del (p.Leu3fs)	CEP41	Pathogenic	criteria provided, single submitter
1878640	NM_018718.3(CEP41):c.856C>T (p.Arg286Ter)	CEP41	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2131693	NM_018718.3(CEP41):c.477del (p.Glu160fs)	CEP41	Pathogenic	criteria provided, single submitter
2740806	NM_018718.3(CEP41):c.880del (p.Leu294fs)	CEP41	Pathogenic	criteria provided, single submitter
280165	NM_018718.3(CEP41):c.418C>T (p.Gln140Ter)	CEP41	Pathogenic	criteria provided, multiple submitters, no conflicts
30838	NM_018718.3(CEP41):c.33+2T>G	CEP41	Pathogenic	no assertion criteria provided
30839	NM_018718.3(CEP41):c.97+3_97+5del	CEP41	Pathogenic	no assertion criteria provided
30840	NM_018718.3(CEP41):c.423-2A>C	CEP41	Pathogenic	criteria provided, multiple submitters, no conflicts
30844	NM_018718.3(CEP41):c.83C>A (p.Ser28Ter)	CEP41	Pathogenic	no assertion criteria provided
3621567	NM_018718.3(CEP41):c.55C>T (p.Gln19Ter)	CEP41	Pathogenic	criteria provided, single submitter
3650399	NM_018718.3(CEP41):c.542_545del (p.Arg181fs)	CEP41	Pathogenic	criteria provided, single submitter
3708774	NM_018718.3(CEP41):c.156del (p.Arg51_Tyr52insTer)	CEP41	Pathogenic	criteria provided, single submitter
4725805	NM_018718.3(CEP41):c.313_314dup (p.Thr106fs)	CEP41	Pathogenic	criteria provided, single submitter
954659	NM_018718.3(CEP41):c.423-2A>G	CEP41	Pathogenic	criteria provided, single submitter
1471398	NM_018718.3(CEP41):c.278-1G>A	CEP41	Likely pathogenic	criteria provided, single submitter
1958588	NM_018718.3(CEP41):c.757+2T>A	CEP41	Likely pathogenic	criteria provided, single submitter
2752461	NM_018718.3(CEP41):c.98-2A>G	CEP41	Likely pathogenic	criteria provided, single submitter
4739999	NM_018718.3(CEP41):c.643-1G>A	CEP41	Likely pathogenic	criteria provided, single submitter
692046	NM_018718.3(CEP41):c.942_943del (p.Glu315fs)	CEP41	Likely pathogenic	criteria provided, single submitter
235611	NM_018718.3(CEP41):c.320C>G (p.Ala107Gly)	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358935	NM_018718.3(CEP41):c.*593G>A	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358939	NM_018718.3(CEP41):c.1009T>C (p.Ser337Pro)	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358941	NM_018718.3(CEP41):c.988G>C (p.Ala330Pro)	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358942	NM_018718.3(CEP41):c.616C>G (p.Pro206Ala)	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
384130	NM_018718.3(CEP41):c.278-15A>T	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
390041	NM_018718.3(CEP41):c.422+7G>A	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
508800	NM_018718.3(CEP41):c.278-15A>C	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
631996	NM_018718.3(CEP41):c.976C>T (p.Arg326Ter)	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
707167	NM_018718.3(CEP41):c.20T>C (p.Ile7Thr)	CEP41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
CEP41	Definitive	Autosomal recessive	Joubert syndrome 15	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP41	Orphanet:220493	Joubert syndrome with ocular defect
CEP41	Orphanet:475	Isolated Joubert syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CEP41	HGNC:12370	ENSG00000106477	Q9BYV8	Centrosomal protein of 41 kDa	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP41	Centrosomal protein of 41 kDa	Required during ciliogenesis for tubulin glutamylation in cilium.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP41	Other/Unknown	no		Rhodanese-like_dom, Rhodanese-like_dom_sf, CEP41

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP41	237	ubiquitous	marker	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP41	944

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP41	Q9BYV8	71.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 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×	0.013	CEP41
Loss of Nlp from mitotic centrosomes	1	158.6×	0.013	CEP41
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.013	CEP41
AURKA Activation by TPX2	1	152.3×	0.013	CEP41
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.013	CEP41
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.013	CEP41
Mitotic G2-G2/M phases	1	126.9×	0.013	CEP41
G2/M Transition	1	126.9×	0.013	CEP41
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.013	CEP41
Anchoring of the basal body to the plasma membrane	1	113.1×	0.013	CEP41
Cilium Assembly	1	108.8×	0.013	CEP41
Mitotic Prometaphase	1	69.2×	0.017	CEP41
Organelle biogenesis and maintenance	1	66.0×	0.017	CEP41
M Phase	1	66.0×	0.017	CEP41
Cell Cycle, Mitotic	1	48.2×	0.022	CEP41
Cell Cycle	1	36.0×	0.028	CEP41

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein polyglutamylation	1	2808.7×	0.001	CEP41
cilium assembly	1	73.6×	0.020	CEP41
protein transport	1	43.9×	0.023	CEP41

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
CEP41	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	CEP41

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP41	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.