Joubert syndrome 10

Summary

Joubert syndrome 10 (MONDO:0010431) is a disease caused by OFD1 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: OFD1 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 154

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 10
Mondo ID	MONDO:0010431
MeSH	C567582
OMIM	300804
DOID	DOID:0110981
UMLS	C2749019
MedGen	440688
GARD	0015265
Is cancer (heuristic)	no

Also known as: JBTS10 · Joubert syndrome 10 · Joubert syndrome 10, X-linked recessive · Joubert syndrome caused by mutation in OFD1 · Joubert syndrome type 10 · OFD1 Joubert syndrome

Data availability: 154 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 10

Related subtypes (38): Joubert syndrome 1, 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 17, 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

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

154 retrieved; paginated sample, class counts are floors:

85 uncertain significance, 22 conflicting classifications of pathogenicity, 19 benign/likely benign, 11 pathogenic, 6 likely pathogenic, 6 likely benign, 3 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
982095	NM_001378615.1(CC2D2A):c.4555T>C (p.Trp1519Arg)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11544	NM_003611.3(OFD1):c.2844_2850del (p.Lys948fs)	OFD1	Pathogenic	no assertion criteria provided
11545	NM_003611.3(OFD1):c.2767del (p.Glu923fs)	OFD1	Pathogenic	criteria provided, single submitter
1179099	NM_003611.3(OFD1):c.1411+1G>A	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
217685	NM_003611.3(OFD1):c.277G>T (p.Val93Phe)	OFD1	Pathogenic	criteria provided, single submitter
217686	NM_003611.3(OFD1):c.2668C>T (p.Arg890Ter)	OFD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35485	NM_003611.3(OFD1):c.689_706del (p.Ile230_Lys235del)	OFD1	Pathogenic	no assertion criteria provided
3598083	NM_003611.3(OFD1):c.1604dup (p.Leu535fs)	OFD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41065	NM_003611.3(OFD1):c.1193_1196del (p.Gln398fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
41066	NM_003611.3(OFD1):c.121C>T (p.Arg41Ter)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
41117	NM_003611.3(OFD1):c.400_403del (p.Glu134fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
41143	NM_003611.3(OFD1):c.710dup (p.Tyr238fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
4819659	NM_003611.3(OFD1):c.721G>T (p.Glu241Ter)	OFD1	Pathogenic	criteria provided, single submitter
978060	NM_003611.3(OFD1):c.599T>C (p.Leu200Pro)	OFD1	Pathogenic	criteria provided, single submitter
1331351	NM_003611.3(OFD1):c.2484dup (p.Glu829Ter)	OFD1	Likely pathogenic	criteria provided, single submitter
2584778	NM_003611.3(OFD1):c.1972A>T (p.Lys658Ter)	OFD1	Likely pathogenic	no assertion criteria provided
3382813	NM_003611.3(OFD1):c.1597_1598del (p.Lys533fs)	OFD1	Likely pathogenic	criteria provided, single submitter
3598070	NM_003611.3(OFD1):c.1055+1G>T	OFD1	Likely pathogenic	criteria provided, single submitter
430297	NM_003611.3(OFD1):c.538GAT[1] (p.Asp181del)	OFD1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
976442	NM_003611.3(OFD1):c.2387+1G>A	OFD1	Likely pathogenic	no assertion criteria provided
1106239	NM_003611.3(OFD1):c.1015G>A (p.Glu339Lys)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1167595	NM_003611.3(OFD1):c.494C>T (p.Ser165Leu)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1298390	NM_003611.3(OFD1):c.1030C>T (p.Arg344Ter)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1336345	NM_003611.3(OFD1):c.2726G>A (p.Arg909Gln)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1630578	NM_003611.3(OFD1):c.3027C>G (p.Asp1009Glu)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1911357	NM_003611.3(OFD1):c.2672G>A (p.Arg891Lys)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2083669	NM_003611.3(OFD1):c.2928+7G>A	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211787	NM_003611.3(OFD1):c.2584T>G (p.Ser862Ala)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2142621	NM_003611.3(OFD1):c.2940G>C (p.Lys980Asn)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217687	NM_003611.3(OFD1):c.149A>G (p.His50Arg)	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 13 · 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
OFD1	Definitive	X-linked	Joubert syndrome 10	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa
CC2D2A	Orphanet:1454	Joubert syndrome with hepatic defect
CC2D2A	Orphanet:2318	Joubert syndrome with oculorenal defect
CC2D2A	Orphanet:564	Meckel syndrome
CC2D2A	Orphanet:791	Retinitis pigmentosa
PKD1	Orphanet:730	Autosomal dominant polycystic kidney disease
PKD1	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
PRKD1	Orphanet:276145	Malignant epithelial tumor of salivary glands
PRKD1	Orphanet:708019	Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	gencc,clinvar
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	clinvar
PRKD1	HGNC:9407	ENSG00000184304	Q15139	Serine/threonine-protein kinase D1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.
CC2D2A	Coiled-coil and C2 domain-containing protein 2A	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
PKD1	Polycystin-1	Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B.
PRKD1	Serine/threonine-protein kinase D1	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr…

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

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
Protease	1	9.2×	0.182
Antibody/Immunoglobulin	1	7.3×	0.182
Kinase	1	6.9×	0.182
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OFD1	Other/Unknown	no		LisH, OFD1
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
cervix squamous epithelium	1
sperm	1
bronchus	1
right uterine tube	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
seminal vesicle	1
thoracic aorta	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OFD1	2,878
PRKD1	2,131
PKD1	1,370
CC2D2A	899

Intra-cohort edges

A	B	Sources
CC2D2A	OFD1	biogrid_interaction, intact, string_interaction
PKD1	PRKD1	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PKD1	P98161	13

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CC2D2A	Q9P2K1	69.46
PRKD1	Q15139	68.99
OFD1	O75665	68.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	2	56.5×	0.007	OFD1, CC2D2A
VxPx cargo-targeting to cilium	1	129.8×	0.045	PKD1
Sphingolipid de novo biosynthesis	1	71.4×	0.045	PRKD1
Hedgehog ‘off’ state	1	44.6×	0.045	OFD1
Sphingolipid metabolism	1	42.0×	0.045	PRKD1
Loss of Nlp from mitotic centrosomes	1	39.6×	0.045	OFD1
Loss of proteins required for interphase microtubule organization from the centrosome	1	39.6×	0.045	OFD1
AURKA Activation by TPX2	1	38.1×	0.045	OFD1
Recruitment of mitotic centrosome proteins and complexes	1	34.0×	0.045	OFD1
Regulation of PLK1 Activity at G2/M Transition	1	31.7×	0.045	OFD1
Recruitment of NuMA to mitotic centrosomes	1	29.1×	0.045	OFD1
Cilium Assembly	1	27.2×	0.045	CC2D2A
Organelle biogenesis and maintenance	1	16.5×	0.068	CC2D2A
Metabolism of lipids	1	7.9×	0.130	PRKD1
Metabolism	1	2.9×	0.302	PRKD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
axoneme assembly	2	271.8×	0.002	OFD1, CC2D2A
metanephric distal tubule morphogenesis	1	4213.0×	0.007	PKD1
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	2106.5×	0.007	PRKD1
nitrogen cycle metabolic process	1	2106.5×	0.007	PKD1
mesonephric tubule development	1	2106.5×	0.007	PKD1
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	2106.5×	0.007	OFD1
kidney development	2	70.2×	0.007	CC2D2A, PKD1
lymph vessel morphogenesis	1	1404.3×	0.008	PKD1
metanephric proximal tubule development	1	1404.3×	0.008	PKD1
calcium-independent cell-matrix adhesion	1	1053.2×	0.008	PKD1
cellular response to norepinephrine stimulus	1	1053.2×	0.008	PRKD1
metanephric ascending thin limb development	1	1053.2×	0.008	PKD1
heart development	2	39.4×	0.008	CC2D2A, PKD1
cilium assembly	2	36.8×	0.008	OFD1, CC2D2A
mesonephric duct development	1	842.6×	0.008	PKD1
positive regulation of sarcomere organization	1	702.2×	0.009	PRKD1
mitocytosis	1	702.2×	0.009	PKD1
protein localization to ciliary transition zone	1	601.9×	0.009	CC2D2A
embryonic body morphogenesis	1	526.6×	0.009	OFD1
lung epithelium development	1	526.6×	0.009	PKD1
cellular response to hydroperoxide	1	526.6×	0.009	PRKD1
regulation of integrin-mediated signaling pathway	1	526.6×	0.009	PRKD1
response to fluid shear stress	1	468.1×	0.010	PKD1
genitalia development	1	421.3×	0.010	PKD1
metanephric collecting duct development	1	421.3×	0.010	PKD1
regulation of keratinocyte proliferation	1	383.0×	0.010	PRKD1
Golgi vesicle transport	1	383.0×	0.010	PRKD1
positive regulation of peptide hormone secretion	1	383.0×	0.010	PRKD1
placenta blood vessel development	1	351.1×	0.010	PKD1
cellular response to endothelin	1	351.1×	0.010	PRKD1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKD1	26	4
OFD1	0	0
CC2D2A	0	0
PKD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRKD1	660	Binding:650, Functional:10
PKD1	27	Binding:27

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKD1	2.7.11.13	protein kinase C

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

26 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)
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PKD1
D	Druggable family + AlphaFold only, no drug	1	CC2D2A
E	Difficult family or no structure, no drug	1	OFD1

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)
PKD1	27	PRKD1
OFD1	0	—
CC2D2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.