Joubert syndrome 27

Summary

Joubert syndrome 27 (MONDO:0014927) is a disease caused by B9D1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: B9D1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 27
Mondo ID	MONDO:0014927
OMIM	617120
DOID	DOID:0110996
UMLS	C4310706
MedGen	934673
GARD	0016194
Is cancer (heuristic)	no

Also known as: B9D1 Joubert syndrome · JBTS27 · Joubert syndrome 27 · Joubert syndrome caused by mutation in B9D1 · Joubert syndrome type 27

Data availability: 18 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 27

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 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

18 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 conflicting classifications of pathogenicity, 3 benign, 2 likely pathogenic, 2 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
217554	NM_015681.6(B9D1):c.466C>T (p.Arg156Trp)	B9D1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254680	NM_015681.6(B9D1):c.517GTG[1] (p.Val174del)	B9D1	Pathogenic	no assertion criteria provided
31102	NM_015681.6(B9D1):c.341+2T>C	B9D1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1064604	NM_015681.6(B9D1):c.341G>A (p.Arg114Gln)	B9D1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687049	NM_015681.6(B9D1):c.529G>C (p.Asp177His)	B9D1	Likely pathogenic	criteria provided, single submitter
217555	NM_015681.6(B9D1):c.95A>G (p.Tyr32Cys)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
254678	NM_015681.6(B9D1):c.467G>A (p.Arg156Gln)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
376895	NM_001321218.2(B9D1):c.473-1G>C	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
663790	NM_015681.6(B9D1):c.151T>C (p.Ser51Pro)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889437	NM_015681.6(B9D1):c.568A>T (p.Thr190Ser)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033788	NM_015681.6(B9D1):c.472+107G>A	B9D1	Uncertain significance	criteria provided, single submitter
1162243	NM_015681.6(B9D1):c.341G>C (p.Arg114Pro)	B9D1	Uncertain significance	criteria provided, single submitter
1679841	NM_015681.6(B9D1):c.338G>C (p.Gly113Ala)	B9D1	Uncertain significance	criteria provided, single submitter
3391288	NM_015681.6(B9D1):c.63+3G>T	B9D1	Uncertain significance	criteria provided, single submitter
983354	NM_001321219.2(B9D1):c.425C>A (p.Ser142Ter)	B9D1	Uncertain significance	criteria provided, single submitter
1192493	NM_001321218.2(B9D1):c.*61C>T	B9D1	Benign	criteria provided, multiple submitters, no conflicts
260675	NM_015681.6(B9D1):c.472+28C>T	B9D1	Benign	criteria provided, multiple submitters, no conflicts
674719	NM_015681.6(B9D1):c.63+23G>A	LOC130060455	Benign	criteria provided, multiple submitters, no conflicts

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
B9D1	Strong	Autosomal recessive	Joubert syndrome 27	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
B9D1	Orphanet:475	Isolated Joubert syndrome
B9D1	Orphanet:564	Meckel 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
B9D1	HGNC:24123	ENSG00000108641	Q9UPM9	B9 domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
B9D1	B9 domain-containing protein 1	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.

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)
B9D1	Other/Unknown	no		C2_B9-type_dom

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
adenohypophysis	1
left testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
B9D1	224	ubiquitous	marker	right uterine tube, adenohypophysis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
B9D1	765

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
B9D1	Q9UPM9	83.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	B9D1
Cilium Assembly	1	108.8×	0.014	B9D1
Organelle biogenesis and maintenance	1	66.0×	0.015	B9D1

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
neuroepithelial cell differentiation	1	1532.0×	0.004	B9D1
vasculature development	1	1123.5×	0.004	B9D1
camera-type eye development	1	358.6×	0.007	B9D1
embryonic digit morphogenesis	1	300.9×	0.007	B9D1
regulation of protein localization	1	205.5×	0.007	B9D1
smoothened signaling pathway	1	181.2×	0.007	B9D1
cilium assembly	1	73.6×	0.014	B9D1
in utero embryonic development	1	72.0×	0.014	B9D1

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
B9D1	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	B9D1

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)
B9D1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.