Joubert syndrome 33

Summary

Joubert syndrome 33 (MONDO:0033311) is a disease caused by PIBF1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PIBF1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 33
Mondo ID	MONDO:0033311
OMIM	617767
DOID	DOID:0080279
UMLS	C4540389
MedGen	1615779
GARD	0025793
Is cancer (heuristic)	no

Also known as: JBTS33 · Joubert syndrome 33

Data availability: 33 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 33

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 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 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

33 retrieved; paginated sample, class counts are floors:

8 conflicting classifications of pathogenicity, 7 likely pathogenic, 5 uncertain significance, 5 pathogenic, 3 benign, 3 benign/likely benign, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
446198	NM_006346.4(PIBF1):c.1910A>C (p.Asp637Ala)	PIBF1	Pathogenic	no assertion criteria provided
446200	NM_006346.4:c.(672+1_673-1)_(1322+1_1323-1)del	PIBF1	Pathogenic	no assertion criteria provided
599034	NM_006346.4(PIBF1):c.1453C>T (p.Gln485Ter)	PIBF1	Pathogenic	no assertion criteria provided
632607	NM_006346.4(PIBF1):c.1918A>T (p.Ile640Phe)	PIBF1	Pathogenic/Likely pathogenic	no assertion criteria provided
807653	NM_006346.4(PIBF1):c.1801C>T (p.Arg601Ter)	PIBF1	Pathogenic	criteria provided, single submitter
981932	NM_006346.4(PIBF1):c.1181_1182insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA (p.Arg385_Arg396dup)	PIBF1	Pathogenic	no assertion criteria provided
1324895	NM_006346.4(PIBF1):c.1213C>T (p.Arg405Ter)	PIBF1	Likely pathogenic	criteria provided, single submitter
1332798	NM_006346.4(PIBF1):c.1150_1151insCAGATTGAAAACCAACCAAGAAATTGATCAGCTTCG (p.Ile384delinsThrAspTer)	PIBF1	Likely pathogenic	criteria provided, single submitter
1687224	NM_006346.4(PIBF1):c.597_598insAAGAAAGGAATCCATTAAGAAAG (p.Glu200delinsLysLysGlyIleHisTer)	PIBF1	Likely pathogenic	criteria provided, single submitter
2412732	NM_006346.4(PIBF1):c.1056_1068del (p.Lys353fs)	PIBF1	Likely pathogenic	criteria provided, single submitter
2691411	NM_006346.4(PIBF1):c.1731-1G>A	PIBF1	Likely pathogenic	criteria provided, single submitter
3338618	NM_006346.4(PIBF1):c.2076_2100del (p.Val693fs)	PIBF1	Likely pathogenic	criteria provided, single submitter
598934	NM_006346.4(PIBF1):c.1508A>G (p.Tyr503Cys)	PIBF1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1572001	NM_006346.4(PIBF1):c.1888A>G (p.Ile630Val)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217689	NM_006346.4(PIBF1):c.1214G>A (p.Arg405Gln)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2396608	NM_006346.4(PIBF1):c.1974_1977del (p.Asn658fs)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2399309	NM_006346.4(PIBF1):c.1124A>G (p.Asn375Ser)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3350966	NM_006346.4(PIBF1):c.1642G>A (p.Glu548Lys)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
770994	NM_006346.4(PIBF1):c.1793T>G (p.Leu598Arg)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
807652	NM_006346.4(PIBF1):c.1133A>C (p.His378Pro)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
996096	NM_006346.4(PIBF1):c.1971_1973delinsT (p.Leu657fs)	PIBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032433	NM_006346.4(PIBF1):c.2113C>A (p.Leu705Ile)	PIBF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2362254	NM_006346.4(PIBF1):c.1931C>T (p.Thr644Met)	PIBF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2574136	NM_006346.4(PIBF1):c.2050-8245_2223+758del	PIBF1	Uncertain significance	criteria provided, single submitter
3418145	NM_006346.4(PIBF1):c.875A>G (p.His292Arg)	PIBF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3777026	NM_006346.4(PIBF1):c.1204A>T (p.Met402Leu)	PIBF1	Uncertain significance	criteria provided, single submitter
1327011	NM_006346.4(PIBF1):c.499A>G (p.Ile167Val)	PIBF1	Benign	criteria provided, multiple submitters, no conflicts
1327012	NM_006346.4(PIBF1):c.672+38G>A	PIBF1	Benign	criteria provided, multiple submitters, no conflicts
1532801	NM_006346.4(PIBF1):c.1223+14_1223+15dup	PIBF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1570235	NM_006346.4(PIBF1):c.1965-4dup	PIBF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
PIBF1	Definitive	Autosomal recessive	Joubert syndrome 33	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PIBF1	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
PIBF1	HGNC:23352	ENSG00000083535	Q8WXW3	Progesterone-induced-blocking factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PIBF1	Progesterone-induced-blocking factor 1	Plays a role in ciliogenesis.

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)
PIBF1	Other/Unknown	no		PIBF1

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
calcaneal tendon	1
sural nerve	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PIBF1	273	ubiquitous	marker	calcaneal tendon, ventricular zone, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIBF1	1,706

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PIBF1	Q8WXW3	77.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
negative regulation of prostaglandin biosynthetic process	1	8426.0×	0.001	PIBF1
negative regulation of tyrosine phosphorylation of STAT protein	1	5617.3×	0.001	PIBF1
activation of Janus kinase activity	1	4213.0×	0.001	PIBF1
negative regulation of natural killer cell activation	1	2106.5×	0.002	PIBF1
negative regulation of interleukin-12 production	1	1053.2×	0.002	PIBF1
positive regulation of tyrosine phosphorylation of STAT protein	1	732.7×	0.003	PIBF1
protein localization to centrosome	1	674.1×	0.003	PIBF1
positive regulation of interleukin-10 production	1	401.2×	0.003	PIBF1
immune system process	1	391.9×	0.003	PIBF1
mitotic metaphase chromosome alignment	1	383.0×	0.003	PIBF1
mitotic spindle assembly	1	343.9×	0.003	PIBF1
non-motile cilium assembly	1	290.6×	0.004	PIBF1
cilium assembly	1	73.6×	0.014	PIBF1

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
PIBF1	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	PIBF1

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)
PIBF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.