Bardet-Biedl syndrome 9

Summary

Bardet-Biedl syndrome 9 (MONDO:0014437) is a disease caused by BBS9 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: BBS9 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 385

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 9
Mondo ID	MONDO:0014437
MeSH	C565918
OMIM	615986
DOID	DOID:0110131
UMLS	C1859567
MedGen	347182
GARD	0010208
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 9 · Bardet-Biedl syndrome caused by mutation in BBS9 · Bardet-Biedl syndrome type 9 · BBS9 · BBS9 Bardet-Biedl syndrome

Data availability: 385 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bardet-Biedl syndrome › Bardet-Biedl syndrome 9

Related subtypes (21): Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 3, Bardet-Biedl syndrome 6, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome 4, Bardet-Biedl syndrome 5, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome 10, Bardet-Biedl syndrome 11, Bardet-Biedl syndrome 12, Bardet-Biedl syndrome 13, Bardet-Biedl syndrome 14, Bardet-Biedl syndrome 15, Bardet-Biedl syndrome 16, Bardet-Biedl syndrome 17, Bardet-Biedl syndrome 18, Bardet-Biedl syndrome 19, Bardet-Biedl syndrome 22, Bardet-Biedl syndrome 20, bardet-biedl syndrome 21

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

385 retrieved; paginated sample, class counts are floors:

199 uncertain significance, 47 likely pathogenic, 29 conflicting classifications of pathogenicity, 23 pathogenic/likely pathogenic, 23 pathogenic, 22 likely benign, 22 benign/likely benign, 20 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073367	NM_198428.3(BBS9):c.1474A>T (p.Lys492Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074680	NM_198428.3(BBS9):c.2007_2008dup (p.Ala670fs)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
1074830	NM_198428.3(BBS9):c.1789C>T (p.Gln597Ter)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
1342593	NM_198428.3(BBS9):c.1540C>T (p.Arg514Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1344653	NM_198428.3(BBS9):c.542C>G (p.Pro181Arg)	BBS9	Pathogenic	no assertion criteria provided
1375465	NM_198428.3(BBS9):c.1175del (p.Ile392fs)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456527	NM_198428.3(BBS9):c.1561C>T (p.Arg521Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685565	NM_198428.3(BBS9):c.702+1G>A	BBS9	Pathogenic	criteria provided, single submitter
1696049	NM_198428.3(BBS9):c.1277_1280del	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1701520	NM_198428.3(BBS9):c.1120C>T (p.Arg374Ter)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
1984986	NM_198428.3(BBS9):c.1022T>A (p.Leu341Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2055946	NM_198428.3(BBS9):c.966G>A (p.Trp322Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2158610	NM_198428.3(BBS9):c.358C>T (p.Gln120Ter)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
216144	NM_198428.3(BBS9):c.1370T>A (p.Leu457Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216145	NM_198428.3(BBS9):c.1423G>T (p.Glu475Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217437	NM_198428.3(BBS9):c.104_112+4del	BBS9	Pathogenic	no assertion criteria provided
2656	NM_198428.3(BBS9):c.1789+1G>A	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2657	NM_198428.3(BBS9):c.1792C>T (p.Arg598Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265771	NM_198428.3(BBS9):c.1759C>T (p.Arg587Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2658	NM_198428.3(BBS9):c.2045dup (p.Arg683fs)	BBS9	Pathogenic	criteria provided, single submitter
2660	NM_198428.3(BBS9):c.1063C>T (p.Gln355Ter)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
2661	NM_198428.3(BBS9):c.442+1G>C	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
266106	NM_198428.3(BBS9):c.223C>T (p.Arg75Ter)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
2662	NM_198428.3(BBS9):c.1877_1880del (p.Lys626fs)	BBS9	Pathogenic	criteria provided, multiple submitters, no conflicts
2680091	NM_198428.3(BBS9):c.434del (p.Gly145fs)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680101	NM_198428.3(BBS9):c.1789+1G>C	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680103	NM_198428.3(BBS9):c.196G>T (p.Glu66Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2754550	NM_198428.3(BBS9):c.2503_2504dup (p.Gln835fs)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2920611	NM_198428.3(BBS9):c.2297T>A (p.Leu766Ter)	BBS9	Pathogenic	no assertion criteria provided
2995997	NM_198428.3(BBS9):c.1099C>T (p.Gln367Ter)	BBS9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 10 · 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
BBS9	Definitive	Autosomal recessive	Bardet-Biedl syndrome 9	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS9	Orphanet:110	Bardet-Biedl syndrome
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BBS9	HGNC:30000	ENSG00000122507	Q3SYG4	Protein PTHB1	gencc,clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS9	Protein PTHB1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BBS9	Other/Unknown	no		PTHB1, PHTB1_N_dom, PHTB1_GAE_dom
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
oocyte	1
secondary oocyte	1
adrenal tissue	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS9	279	ubiquitous	marker	oocyte, secondary oocyte, calcaneal tendon
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540
BBS9	132

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF1	P21359	26
BBS9	Q3SYG4	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAS signaling downstream of NF1 loss-of-function variants	1	815.7×	0.012	NF1
BBSome-mediated cargo-targeting to cilium	1	248.3×	0.020	BBS9
Oncogenic MAPK signaling	1	124.1×	0.026	NF1
Regulation of RAS by GAPs	1	96.8×	0.026	NF1
MAPK1/MAPK3 signaling	1	65.6×	0.030	NF1
MAPK family signaling cascades	1	51.4×	0.032	NF1
RAF/MAP kinase cascade	1	30.5×	0.044	NF1
Diseases of signal transduction by growth factor receptors and second messengers	1	28.4×	0.044	NF1
Disease	1	6.5×	0.163	NF1
Signal Transduction	1	5.1×	0.187	NF1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 mast cell apoptotic process	1	8426.0×	0.003	NF1
regulation of glial cell differentiation	1	8426.0×	0.003	NF1
observational learning	1	8426.0×	0.003	NF1
gamma-aminobutyric acid secretion, neurotransmission	1	4213.0×	0.003	NF1
Schwann cell proliferation	1	2808.7×	0.003	NF1
forebrain astrocyte development	1	2808.7×	0.003	NF1
Schwann cell migration	1	2808.7×	0.003	NF1
glutamate secretion, neurotransmission	1	2808.7×	0.003	NF1
negative regulation of mast cell proliferation	1	2808.7×	0.003	NF1
negative regulation of Schwann cell migration	1	2808.7×	0.003	NF1
vascular associated smooth muscle cell migration	1	2808.7×	0.003	NF1
mast cell apoptotic process	1	2106.5×	0.003	NF1
negative regulation of Rac protein signal transduction	1	2106.5×	0.003	NF1
myeloid leukocyte migration	1	2106.5×	0.003	NF1
mast cell proliferation	1	1685.2×	0.004	NF1
amygdala development	1	1404.3×	0.004	NF1
regulation of blood vessel endothelial cell migration	1	1404.3×	0.004	NF1
vascular associated smooth muscle cell proliferation	1	1404.3×	0.004	NF1
negative regulation of Schwann cell proliferation	1	1203.7×	0.004	NF1
negative regulation of neurotransmitter secretion	1	1203.7×	0.004	NF1
hair follicle maturation	1	1053.2×	0.005	NF1
negative regulation of leukocyte migration	1	842.6×	0.005	NF1
negative regulation of vascular associated smooth muscle cell migration	1	842.6×	0.005	NF1
regulation of bone resorption	1	766.0×	0.005	NF1
negative regulation of astrocyte differentiation	1	766.0×	0.005	NF1
regulation of long-term synaptic potentiation	1	766.0×	0.005	NF1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	766.0×	0.005	NF1
forebrain morphogenesis	1	702.2×	0.005	NF1
regulation of cell-matrix adhesion	1	648.1×	0.005	NF1
negative regulation of neuroblast proliferation	1	601.9×	0.006	NF1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
BBS9	0	0
NF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	BBS9, NF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BBS9	0	—
NF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.