Joubert syndrome 37

Summary

Joubert syndrome 37 (MONDO:0030933) is a disease caused by TOGARAM1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TOGARAM1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 37
Mondo ID	MONDO:0030933
OMIM	619185
UMLS	C5543064
MedGen	1786742
GARD	0016434
Is cancer (heuristic)	no

Also known as: JBTS37 · Joubert syndrome 37

Data availability: 22 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 37

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 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

22 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 7 pathogenic, 6 likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
4689371	NM_001308120.2(TOGARAM1):c.942del (p.Gln314fs)	TOGARAM1	Pathogenic	criteria provided, single submitter
917940	NM_001308120.2(TOGARAM1):c.1102C>T (p.Arg368Trp)	TOGARAM1	Pathogenic	criteria provided, single submitter
979054	NM_001308120.2(TOGARAM1):c.3931C>T (p.Arg1311Cys)	TOGARAM1	Pathogenic	criteria provided, single submitter
979055	NM_001308120.2(TOGARAM1):c.1084C>T (p.Gln362Ter)	TOGARAM1	Pathogenic	criteria provided, single submitter
979058	NM_001308120.2(TOGARAM1):c.3248C>A (p.Ser1083Ter)	TOGARAM1	Pathogenic	criteria provided, single submitter
984438	NM_001308120.2:c.2339_3238del	TOGARAM1	Pathogenic	criteria provided, single submitter
997691	NM_001308120.2(TOGARAM1):c.3619C>T (p.Arg1207Ter)	TOGARAM1	Pathogenic	no assertion criteria provided
1703114	NM_001308120.2(TOGARAM1):c.4150C>T (p.Gln1384Ter)	TOGARAM1	Likely pathogenic	criteria provided, single submitter
1703763	NM_001308120.2(TOGARAM1):c.2338+3A>G	TOGARAM1	Likely pathogenic	criteria provided, single submitter
3362854	NM_001308120.2(TOGARAM1):c.4969+2T>A	TOGARAM1	Likely pathogenic	criteria provided, single submitter
3393417	NM_001308120.2(TOGARAM1):c.76del (p.Ser26fs)	TOGARAM1	Likely pathogenic	criteria provided, single submitter
3892694	NM_001308120.2(TOGARAM1):c.2501_2504del (p.Ile834fs)	TOGARAM1	Likely pathogenic	criteria provided, single submitter
4845913	NM_001308120.2(TOGARAM1):c.1844del (p.Ala615fs)	TOGARAM1	Likely pathogenic	criteria provided, single submitter
979053	NM_001308120.2(TOGARAM1):c.1124T>C (p.Leu375Pro)	TOGARAM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
979060	NM_001308120.2(TOGARAM1):c.5182C>T (p.Arg1728Ter)	TOGARAM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2441935	NM_001308120.2(TOGARAM1):c.2921G>T (p.Arg974Met)	TOGARAM1	Uncertain significance	criteria provided, single submitter
2664208	NM_001308120.2(TOGARAM1):c.4676G>A (p.Arg1559His)	TOGARAM1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3338419	NM_001308120.2(TOGARAM1):c.3239-13G>A	TOGARAM1	Uncertain significance	criteria provided, single submitter
3367059	NM_001308120.2(TOGARAM1):c.2923_2924delinsAA (p.Ser975Asn)	TOGARAM1	Uncertain significance	criteria provided, single submitter
3906888	NM_001308120.2(TOGARAM1):c.3329G>T (p.Gly1110Val)	TOGARAM1	Uncertain significance	criteria provided, single submitter
4080565	NM_001308120.2(TOGARAM1):c.1169C>T (p.Ser390Phe)	TOGARAM1	Uncertain significance	criteria provided, single submitter
4292392	NM_001308120.2(TOGARAM1):c.1562A>G (p.Asp521Gly)	TOGARAM1	Uncertain significance	criteria provided, single submitter

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
TOGARAM1	Strong	Autosomal recessive	Joubert syndrome 37	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TOGARAM1	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
TOGARAM1	HGNC:19959	ENSG00000198718	Q9Y4F4	TOG array regulator of axonemal microtubules protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TOGARAM1	TOG array regulator of axonemal microtubules protein 1	Involved 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)
TOGARAM1	Other/Unknown	no		ARM-like, ARM-type_fold, TOG

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
bronchial epithelial cell	1
epithelium of bronchus	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TOGARAM1	288	ubiquitous	marker	bronchial epithelial cell, tibia, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TOGARAM1	731

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TOGARAM1	Q9Y4F4	62.26

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
positive regulation of microtubule polymerization	1	674.1×	0.005	TOGARAM1
axoneme assembly	1	543.6×	0.005	TOGARAM1
non-motile cilium assembly	1	290.6×	0.006	TOGARAM1
microtubule cytoskeleton organization	1	121.2×	0.010	TOGARAM1
cilium assembly	1	73.6×	0.014	TOGARAM1

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
TOGARAM1	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	TOGARAM1

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)
TOGARAM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.