Joubert syndrome 36

Summary

Joubert syndrome 36 (MONDO:0032902) is a disease caused by FAM149B1 (GenCC Strong), with 4 cohort genes.

At a glance

• Causal gene: FAM149B1 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 36
Mondo ID	MONDO:0032902
OMIM	618763
UMLS	C5231493
MedGen	1684786
GARD	0016376
Is cancer (heuristic)	no

Also known as: JBTS36

Data availability: 16 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 36

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 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

16 retrieved; paginated sample, class counts are floors:

7 likely pathogenic, 4 uncertain significance, 4 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3237481	NM_173348.2(FAM149B1):c.1198C>T (p.Arg400Ter)	DNAJC9	Pathogenic	criteria provided, single submitter
3237515	NM_173348.2(FAM149B1):c.1127+1G>A	FAM149B1	Pathogenic	criteria provided, single submitter
4291085	NM_173348.2(FAM149B1):c.574dup (p.Ser192fs)	FAM149B1	Pathogenic	criteria provided, single submitter
810830	NM_173348.2(FAM149B1):c.439C>T (p.Gln147Ter)	FAM149B1	Pathogenic	no assertion criteria provided
2505233	NM_173348.2(FAM149B1):c.1183C>T (p.Arg395Ter)	DNAJC9	Likely pathogenic	criteria provided, single submitter
3065140	NM_173348.2(FAM149B1):c.1402C>T (p.Arg468Ter)	DNAJC9	Likely pathogenic	criteria provided, single submitter
3597261	NM_173348.2(FAM149B1):c.898+1del	FAM149B1	Likely pathogenic	criteria provided, single submitter
4291084	NM_173348.2(FAM149B1):c.279T>A (p.Tyr93Ter)	FAM149B1	Likely pathogenic	criteria provided, single submitter
810829	NM_173348.2(FAM149B1):c.356_357del (p.Lys119fs)	FAM149B1	Likely pathogenic	criteria provided, single submitter
996338	NM_016199.3(LSM7):c.206G>C (p.Arg69Pro)	LSM7	Likely pathogenic	criteria provided, single submitter
3220914	NM_152730.6(TBC1D32):c.3724C>T (p.Arg1242Ter)	TBC1D32	Likely pathogenic	criteria provided, single submitter
2689040	NM_173348.2(FAM149B1):c.1189T>G (p.Trp397Gly)	DNAJC9	Uncertain significance	criteria provided, single submitter
2689041	NM_173348.2(FAM149B1):c.1563_1567del (p.Asp522fs)	DNAJC9	Uncertain significance	criteria provided, single submitter
3891686	NM_173348.2(FAM149B1):c.1654C>T (p.Arg552Ter)	DNAJC9	Uncertain significance	criteria provided, single submitter
3148839	NM_173348.2(FAM149B1):c.2T>G (p.Met1Arg)	FAM149B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891687	NM_173348.2(FAM149B1):c.1714_1728del (p.Gly572_Ser576del)	DNAJC9	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
FAM149B1	Strong	Autosomal recessive	Joubert syndrome 36	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FAM149B1	Orphanet:2754	Orofaciodigital syndrome type 6
TBC1D32	Orphanet:141007	Orofaciodigital syndrome type 9

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
FAM149B1	HGNC:29162	ENSG00000138286	Q96BN6	Primary cilium assembly protein FAM149B1	gencc,clinvar
DNAJC9	HGNC:19123	ENSG00000213551	Q8WXX5	DnaJ homolog subfamily C member 9	clinvar
LSM7	HGNC:20470	ENSG00000130332	Q9UK45	U6 snRNA-associated Sm-like protein LSm7	clinvar
TBC1D32	HGNC:21485	ENSG00000146350	Q96NH3	Protein broad-minded	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FAM149B1	Primary cilium assembly protein FAM149B1	Involved in the localization of proteins to the cilium and cilium assembly.
DNAJC9	DnaJ homolog subfamily C member 9	Acts as a dual histone chaperone and heat shock co-chaperone.
LSM7	U6 snRNA-associated Sm-like protein LSm7	Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).
TBC1D32	Protein broad-minded	Required for high-level Shh responses in the developing neural tube.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FAM149B1	Other/Unknown	no		DUF3719, FAM149
DNAJC9	Other/Unknown	no		DnaJ_domain, DnaJ_domain_CS, J_dom_sf
LSM7	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm7
TBC1D32	Other/Unknown	no		BROMI_M, Rab-GAP_TBC_sf, PHAF1/BROMI

Expression context

Cohort genes with no expression data: 0.

3 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
ventricular zone	2
ganglionic eminence	2
C1 segment of cervical spinal cord	1
calcaneal tendon	1
secondary oocyte	1
granulocyte	1
mucosa of transverse colon	1
adrenal tissue	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FAM149B1	265	ubiquitous	marker	C1 segment of cervical spinal cord, ventricular zone, calcaneal tendon
DNAJC9	267	ubiquitous	marker	secondary oocyte, ganglionic eminence, ventricular zone
LSM7	287	ubiquitous	marker	mucosa of transverse colon, granulocyte, ganglionic eminence
TBC1D32	208	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAJC9	3,291
LSM7	2,516
TBC1D32	919
FAM149B1	903

Intra-cohort edges

A	B	Sources
DNAJC9	FAM149B1	string_interaction
FAM149B1	TBC1D32	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LSM7	Q9UK45	20
DNAJC9	Q8WXX5	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBC1D32	Q96NH3	80.84
FAM149B1	Q96BN6	52.50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 4 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
Deadenylation-dependent mRNA decay	1	878.5×	0.004	LSM7
mRNA decay by 5’ to 3’ exoribonuclease	1	761.3×	0.004	LSM7
mRNA Splicing	1	109.8×	0.018	LSM7
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.018	LSM7
mRNA Splicing - Major Pathway	1	54.6×	0.022	LSM7
Metabolism of RNA	1	41.7×	0.024	LSM7

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
protein localization to cilium	2	200.6×	5e-04	FAM149B1, TBC1D32
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	1	1053.2×	0.007	TBC1D32
retinal pigment epithelium development	1	421.3×	0.011	TBC1D32
positive regulation of ATP-dependent activity	1	351.1×	0.011	DNAJC9
nuclear-transcribed mRNA catabolic process	1	191.5×	0.016	LSM7
lens development in camera-type eye	1	93.6×	0.024	TBC1D32
embryonic digit morphogenesis	1	75.2×	0.024	TBC1D32
non-motile cilium assembly	1	72.6×	0.024	TBC1D32
determination of left/right symmetry	1	63.8×	0.024	TBC1D32
roof of mouth development	1	62.0×	0.024	TBC1D32
kidney development	1	35.1×	0.035	TBC1D32
nucleosome assembly	1	35.1×	0.035	DNAJC9
mRNA splicing, via spliceosome	1	22.9×	0.050	LSM7
heart development	1	19.7×	0.053	TBC1D32
cilium assembly	1	18.4×	0.053	FAM149B1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FAM149B1	0	0
DNAJC9	0	0
LSM7	0	0
TBC1D32	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
DNAJC9	7	Binding:7

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

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	4	FAM149B1, DNAJC9, LSM7, TBC1D32

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FAM149B1	0	—
DNAJC9	7	—
LSM7	0	—
TBC1D32	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.