Joubert syndrome 17

Summary

Joubert syndrome 17 (MONDO:0013824) is a disease caused by CPLANE1 (GenCC Definitive), with 6 cohort genes.

At a glance

• Causal gene: CPLANE1 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 835

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 17
Mondo ID	MONDO:0013824
OMIM	614615
DOID	DOID:0110986
NCIT	C175702
UMLS	C3553264
MedGen	766178
GARD	0015824
Is cancer (heuristic)	no

Also known as: CPLANE1 Joubert syndrome · JBTS17 · Joubert syndrome 17 · Joubert syndrome caused by mutation in CPLANE1 · Joubert syndrome type 17

Data availability: 835 ClinVar variants · 4 GenCC gene-disease records · 4 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 17

Related subtypes (38): Joubert syndrome 1, Joubert syndrome 10, Joubert syndrome 2, Joubert syndrome 3, Joubert syndrome with renal defect, Joubert syndrome 5, Joubert syndrome 6, Joubert syndrome 7, Joubert syndrome 9, Joubert syndrome 8, Joubert syndrome 13, Joubert syndrome 14, Joubert syndrome 15, Joubert syndrome 16, Joubert syndrome 18, Joubert syndrome 20, Joubert syndrome 21, Joubert syndrome 22, Joubert syndrome 23, Joubert syndrome 24, Joubert syndrome 25, Joubert syndrome 26, Joubert syndrome 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 40, Joubert syndrome 37, Joubert syndrome 35, Joubert syndrome 36, Joubert syndrome 30, Joubert syndrome 32, Joubert syndrome 31, Joubert syndrome 33, Joubert syndrome 19, Joubert syndrome 29, Joubert syndrome 11, Joubert syndrome 34

Subtypes (1): orofaciodigital syndrome type 6

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:

339 uncertain significance, 72 conflicting classifications of pathogenicity, 40 pathogenic, 39 likely pathogenic, 31 likely benign, 29 pathogenic/likely pathogenic, 26 benign/likely benign, 24 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030823	NM_001384732.1(CPLANE1):c.9046C>T (p.Arg3016Ter)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1202647	NM_001384732.1(CPLANE1):c.6354dup (p.Ile2119fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332773	NM_001384732.1(CPLANE1):c.7020dup (p.Leu2341fs)	CPLANE1	Pathogenic	criteria provided, single submitter
1334387	NM_001384732.1(CPLANE1):c.2563C>T (p.Gln855Ter)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369735	NM_001384732.1(CPLANE1):c.6477del (p.Ser2160fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1416162	NM_001384732.1(CPLANE1):c.3599C>A (p.Ala1200Glu)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1444291	NM_001384732.1(CPLANE1):c.3829dup (p.Cys1277fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451420	NM_001384732.1(CPLANE1):c.7402C>T (p.Gln2468Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
1456393	NM_001384732.1(CPLANE1):c.7032del (p.Lys2345fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456531	NM_001384732.1(CPLANE1):c.4155dup (p.Leu1386fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
157513	NM_001384732.1(CPLANE1):c.493del (p.Ile165fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
157514	NM_001384732.1(CPLANE1):c.3290-2A>G	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
157515	NM_001384732.1(CPLANE1):c.3380C>T (p.Ser1127Leu)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723410	NM_001384732.1(CPLANE1):c.3056_3059dup (p.Trp1020fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805055	NM_001384732.1(CPLANE1):c.7378C>T (p.Gln2460Ter)	CPLANE1	Pathogenic	criteria provided, single submitter
183307	NM_001384732.1(CPLANE1):c.8150_8151del (p.Gly2717fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
1917445	NM_001384732.1(CPLANE1):c.3094_3095del (p.Val1032fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
194120	NM_001384732.1(CPLANE1):c.1819dup (p.Tyr607fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
194561	NM_001384732.1(CPLANE1):c.2624C>T (p.Ser875Phe)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217561	NM_001384732.1(CPLANE1):c.8887del (p.Ala2963fs)	CPLANE1	Pathogenic	criteria provided, single submitter
217562	NM_001384732.1(CPLANE1):c.8329C>T (p.Gln2777Ter)	CPLANE1	Pathogenic	criteria provided, single submitter
217563	NM_001384732.1(CPLANE1):c.8878G>T (p.Glu2960Ter)	CPLANE1	Pathogenic	criteria provided, single submitter
217564	NM_001384732.1(CPLANE1):c.9017+1G>A	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217565	NM_001384732.1(CPLANE1):c.8425_8426insG (p.Thr2809fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217566	NM_001384732.1(CPLANE1):c.8140C>T (p.Arg2714Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217567	NM_001384732.1(CPLANE1):c.8770G>T (p.Glu2924Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217568	NM_001384732.1(CPLANE1):c.7190del (p.Pro2397fs)	CPLANE1	Pathogenic	criteria provided, single submitter
217569	NM_001384732.1(CPLANE1):c.9220C>T (p.Arg3074Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217570	NM_001384732.1(CPLANE1):c.8425dup (p.Thr2809fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217571	NM_001384732.1(CPLANE1):c.8872C>T (p.Arg2958Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 14 · 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
CPLANE1	Definitive	Autosomal recessive	Joubert syndrome 17	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPLANE1	Orphanet:2754	Orofaciodigital syndrome type 6
CPLANE1	Orphanet:475	Isolated Joubert syndrome
CPLANE1	Orphanet:65684	Monomelic amyotrophy
COQ8A	Orphanet:139485	Autosomal recessive ataxia due to ubiquinone deficiency
CRB2	Orphanet:443988	Ventriculomegaly-cystic kidney disease
CRB2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
CR2	Orphanet:536	Systemic lupus erythematosus
CR2	Orphanet:696894	Common variable immunodeficiency phenotype due to CD21 deficiency
CRYGD	Orphanet:1377	Cataract-microcornea syndrome
CRYGD	Orphanet:441452	Early-onset lamellar cataract
CRYGD	Orphanet:98984	Pulverulent cataract
CRYGD	Orphanet:98989	Cerulean cataract
CRYGD	Orphanet:98990	Coralliform cataract
CRYGD	Orphanet:98991	Early-onset nuclear cataract

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	gencc,clinvar
COQ8A	HGNC:16812	ENSG00000163050	Q8NI60	Atypical kinase COQ8A, mitochondrial	clinvar
CRB2	HGNC:18688	ENSG00000148204	Q5IJ48	Protein crumbs homolog 2	clinvar
CR2	HGNC:2336	ENSG00000117322	P20023	Complement receptor type 2	clinvar
CRYGD	HGNC:2411	ENSG00000118231	P07320	Gamma-crystallin D	clinvar
CPLANE1-AS1	HGNC:56117	ENSG00000286193		CPLANE1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.
COQ8A	Atypical kinase COQ8A, mitochondrial	Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.
CRB2	Protein crumbs homolog 2	Apical polarity protein that plays a central role during the epithelial-to-mesenchymal transition (EMT) at gastrulation, when newly specified mesodermal cells move inside the embryo.
CR2	Complement receptor type 2	Serves as a receptor for various ligands including complement component CD3d, HNRNPU OR IFNA1.
CRYGD	Gamma-crystallin D	Crystallins are the dominant structural components of the vertebrate eye lens.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · 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.

Family	Genes	Fold	FDR
Complement	1	44.7×	0.089
Kinase	1	4.6×	0.396
Scaffold/PPI	1	2.9×	0.401
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
COQ8A	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK3_dom
CRB2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
CR2	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
CRYGD	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CPLANE1-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

5 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	4
sural nerve	2
ventricular zone	2
calcaneal tendon	1
gastrocnemius	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1
ganglionic eminence	1
oocyte	1
secondary oocyte	1
spleen	1
primordial germ cell in gonad	1
bone marrow cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
COQ8A	134	ubiquitous	marker	gastrocnemius, skeletal muscle tissue, hindlimb stylopod muscle
CRB2	99	broad	marker	ventricular zone, ganglionic eminence, male germ line stem cell (sensu Vertebrata) in testis
CR2	150	broad	marker	secondary oocyte, oocyte, spleen
CRYGD	60	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, ventricular zone
CPLANE1-AS1	132		yes	sural nerve, bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COQ8A	1,765
CRB2	1,640
CR2	1,484
CRYGD	500
CPLANE1	439
CPLANE1-AS1	0

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYGD	P07320	16
CR2	P20023	9
COQ8A	Q8NI60	4
CRB2	Q5IJ48	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPLANE1	Q9H799

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 6 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
Ubiquinol biosynthesis	1	439.2×	0.005	COQ8A
Regulation of Complement cascade	1	116.5×	0.009	CR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ingression involved in gastrulation with mouth forming second	1	3370.4×	0.010	CRB2
notochord formation	1	1123.5×	0.011	CRB2
regulation of gastrulation	1	561.7×	0.011	CRB2
maintenance of epithelial cell apical/basal polarity	1	481.5×	0.011	CRB2
negative regulation of complement activation, classical pathway	1	481.5×	0.011	CR2
visual perception	2	31.8×	0.011	CRB2, CRYGD
negative regulation of endopeptidase activity	1	337.0×	0.012	CRB2
retinal cone cell development	1	280.9×	0.012	CRB2
circulatory system development	1	280.9×	0.012	CRB2
phosphorylation	1	259.3×	0.012	COQ8A
retina homeostasis	1	224.7×	0.012	CRB2
lens fiber cell differentiation	1	210.7×	0.012	CRYGD
T cell mediated immunity	1	198.3×	0.012	CR2
complement activation, alternative pathway	1	198.3×	0.012	CR2
ubiquinone biosynthetic process	1	187.2×	0.012	COQ8A
establishment or maintenance of epithelial cell apical/basal polarity	1	116.2×	0.017	CRB2
complement activation, classical pathway	1	108.7×	0.017	CR2
mesoderm formation	1	99.1×	0.017	CRB2
B cell proliferation	1	96.3×	0.017	CR2
positive regulation of BMP signaling pathway	1	91.1×	0.017	CRB2
B cell activation	1	91.1×	0.017	CR2
cellular response to reactive oxygen species	1	82.2×	0.017	CRYGD
symbiont entry into host cell	1	80.2×	0.017	CR2
establishment of cell polarity	1	76.6×	0.017	CRB2
somitogenesis	1	74.9×	0.017	CRB2
lens development in camera-type eye	1	74.9×	0.017	CRYGD
photoreceptor cell maintenance	1	71.7×	0.017	CRB2
type I interferon-mediated signaling pathway	1	68.8×	0.017	CR2
heterophilic cell-cell adhesion	1	67.4×	0.017	CRB2
positive regulation of epithelial to mesenchymal transition	1	63.6×	0.017	CRB2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 2 of 6 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.

Symbol	Example approved molecule
COQ8A	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COQ8A	14	4
CPLANE1	0	0
CRB2	0	0
CR2	0	0
CRYGD	0	0
CPLANE1-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	COQ8A
VANDETANIB	4	COQ8A
DASATINIB	4	COQ8A
ERLOTINIB	4	COQ8A
SARACATINIB	3	COQ8A
CANERTINIB	3	COQ8A
TG100-115	2	COQ8A
GALUNISERTIB	2	COQ8A
OSI-632	2	COQ8A
R-406	2	COQ8A
MILCICLIB	2	COQ8A
R-1487	1	COQ8A
CYC-116	1	COQ8A
AEW-541	1	COQ8A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
COQ8A	93	Binding:93
CRYGD	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

14 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	COQ8A
VANDETANIB	4	COQ8A
DASATINIB	4	COQ8A
ERLOTINIB	4	COQ8A
SARACATINIB	3	COQ8A
CANERTINIB	3	COQ8A
TG100-115	2	COQ8A
GALUNISERTIB	2	COQ8A
OSI-632	2	COQ8A
R-406	2	COQ8A
MILCICLIB	2	COQ8A
R-1487	1	COQ8A
CYC-116	1	COQ8A
AEW-541	1	COQ8A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	COQ8A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	CR2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	CPLANE1, CRB2, CRYGD, CPLANE1-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CPLANE1	0	—
CRB2	0	—
CR2	0	—
CRYGD	9	—
CPLANE1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.