Joubert syndrome 32

Summary

Joubert syndrome 32 (MONDO:0033309) is a disease caused by SUFU (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SUFU (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 47

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 32
Mondo ID	MONDO:0033309
OMIM	617757
DOID	DOID:0080278
UMLS	C4540342
MedGen	1626697
GARD	0025792
Is cancer (heuristic)	no

Also known as: JBTS32 · Joubert syndrome 32

Data availability: 47 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 32

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 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

47 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 18 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 benign, 1 likely pathogenic, 1 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
446157	NM_016169.4(SUFU):c.527A>G (p.His176Arg)	SUFU	Pathogenic	no assertion criteria provided
406381	NM_016169.4(SUFU):c.1023-2A>T	SUFU	Likely pathogenic	criteria provided, multiple submitters, no conflicts
524666	NM_016169.4(SUFU):c.26C>T (p.Ala9Val)	LOC130004614	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
802631	NM_016169.4(SUFU):c.37A>C (p.Thr13Pro)	LOC130004614	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1319742	NM_016169.4(SUFU):c.31G>C (p.Gly11Arg)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135283	NM_016169.4(SUFU):c.1045A>G (p.Ser349Gly)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135285	NM_016169.4(SUFU):c.1028G>A (p.Arg343His)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135286	NM_016169.4(SUFU):c.1105G>A (p.Val369Ile)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241078	NM_016169.4(SUFU):c.1015C>T (p.Arg339Trp)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241083	NM_016169.4(SUFU):c.169A>G (p.Ile57Val)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406377	NM_016169.4(SUFU):c.992G>A (p.Arg331Gln)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406392	NM_016169.4(SUFU):c.275G>C (p.Ser92Thr)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406398	NM_016169.4(SUFU):c.1058C>T (p.Thr353Met)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406400	NM_016169.4(SUFU):c.1429G>A (p.Val477Met)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
413911	NM_016169.4(SUFU):c.1445C>T (p.Pro482Leu)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
413912	NM_016169.4(SUFU):c.600C>T (p.Ile200=)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
453960	NM_016169.4(SUFU):c.1379A>G (p.Lys460Arg)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
453966	NM_016169.4(SUFU):c.529A>G (p.Met177Val)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
486528	NM_016169.4(SUFU):c.1232C>T (p.Thr411Met)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
860533	NM_016169.4(SUFU):c.664C>G (p.Leu222Val)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
453965	NM_016169.4(SUFU):c.43C>A (p.Pro15Thr)	LOC130004614	Uncertain significance	criteria provided, multiple submitters, no conflicts
582859	NM_016169.4(SUFU):c.32G>A (p.Gly11Asp)	LOC130004614	Uncertain significance	criteria provided, multiple submitters, no conflicts
802630	NM_016169.4(SUFU):c.37_42del (p.Thr13_Ala14del)	LOC130004614	Uncertain significance	criteria provided, multiple submitters, no conflicts
2928584	NM_016169.4(SUFU):c.1372C>A (p.Leu458Ile)	SUFU	Uncertain significance	criteria provided, multiple submitters, no conflicts
2946584	NM_016169.4(SUFU):c.1295A>C (p.Gln432Pro)	SUFU	Uncertain significance	criteria provided, multiple submitters, no conflicts
3236173	NM_016169.4(SUFU):c.1365+5G>C	SUFU	Uncertain significance	criteria provided, single submitter
3377181	NM_016169.4(SUFU):c.122GCC[2] (p.Arg43del)	SUFU	Uncertain significance	criteria provided, single submitter
3377754	NM_016169.4(SUFU):c.164C>T (p.Thr55Ile)	SUFU	Uncertain significance	criteria provided, single submitter
3590249	NM_016169.4(SUFU):c.9G>C (p.Glu3Asp)	SUFU	Uncertain significance	criteria provided, multiple submitters, no conflicts
3590286	NM_016169.4(SUFU):c.1085G>C (p.Arg362Pro)	SUFU	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 7 · 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
SUFU	Strong	Autosomal recessive	Joubert syndrome 32	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome
SUFU	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
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.

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)
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain

Expression context

Cohort genes with no expression data: 0.

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
kidney epithelium	1
upper arm skin	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SUFU	2,188

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SUFU	Q9UMX1	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Degradation of GLI1 by the proteasome	1	223.9×	0.007	SUFU
Degradation of GLI2 by the proteasome	1	223.9×	0.007	SUFU
GLI3 is processed to GLI3R by the proteasome	1	223.9×	0.007	SUFU
Signaling by Hedgehog	1	184.2×	0.007	SUFU
Hedgehog ‘off’ state	1	178.4×	0.007	SUFU
Hedgehog ‘on’ state	1	158.6×	0.007	SUFU
Signal Transduction	1	10.2×	0.098	SUFU

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
positive regulation of cellular response to drug	1	16852.0×	6e-04	SUFU
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	8426.0×	6e-04	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	8426.0×	6e-04	SUFU
maintenance of protein localization in organelle	1	8426.0×	6e-04	SUFU
negative regulation of protein import into nucleus	1	936.2×	0.003	SUFU
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.003	SUFU
dorsal/ventral neural tube patterning	1	802.5×	0.003	SUFU
coronary vasculature development	1	624.1×	0.004	SUFU
aorta development	1	561.7×	0.004	SUFU
ventricular septum development	1	495.6×	0.004	SUFU
negative regulation of smoothened signaling pathway	1	455.5×	0.004	SUFU
skin development	1	443.5×	0.004	SUFU
negative regulation of osteoblast differentiation	1	295.6×	0.005	SUFU
heart looping	1	267.5×	0.005	SUFU
neural tube closure	1	187.2×	0.007	SUFU
spermatid development	1	145.3×	0.008	SUFU
regulation of DNA-templated transcription	1	31.6×	0.035	SUFU
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	SUFU
signal transduction	1	16.1×	0.062	SUFU

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SUFU	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SUFU	1	Binding:1

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	SUFU

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)
SUFU	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.