BBS1-related ciliopathy

Summary

BBS1-related ciliopathy (MONDO:1040043) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	BBS1-related ciliopathy
Mondo ID	MONDO:1040043
GARD	0027245
Is cancer (heuristic)	no

Also known as: BBS1-related ciliopathy

Data availability: 7 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › BBS1-related ciliopathy

Related subtypes (35): Alstrom syndrome, Marden-Walker syndrome, nephronophthisis 1, Bardet-Biedl syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Jeune syndrome, Joubert syndrome, Meckel syndrome, retinal ciliopathy, oculocerebrodental syndrome, CEP290-related ciliopathy, IFT140-related recessive ciliopathy, BBS9-related ciliopathy, BBS10-related ciliopathy, CEP164-related ciliopathy, CFAP418-related ciliopathy, WDPCP-related ciliopathy, SDCCAG8-related ciliopathy, KIF7-related ciliopathy, Alsahan-Harris syndrome, OFD1-related ciliopathy, BBS7-related ciliopathy, BBS4-related ciliopathy, BBS12-related ciliopathy, LZTFL1-related ciliopathy, BBS5-related ciliopathy, BBS2-related ciliopathy, TTC8-related ciliopathy, MKKS-related ciliopathy, ARL6-related ciliopathy, MKS1-related ciliopathy, TUBB4B-related ciliopathy, INTU-related skeletal ciliopathy, ciliopathy-IFT74

Subtypes (1): Bardet-Biedl syndrome 1

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

7 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
698700	NM_024649.5(BBS1):c.1634A>G (p.Asn545Ser)	ZDHHC24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
100591	NM_024649.5(BBS1):c.316C>G (p.Leu106Val)	BBS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2076488	NM_024649.5(BBS1):c.1033G>T (p.Ala345Ser)	BBS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2140380	NM_024649.5(BBS1):c.1244T>G (p.Val415Gly)	BBS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3600125	NM_024649.5(BBS1):c.1345C>T (p.His449Tyr)	BBS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
840005	NM_024649.5(BBS1):c.1310A>T (p.Gln437Leu)	BBS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
12148	NM_024649.5(BBS1):c.700G>A (p.Glu234Lys)	BBS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS1	Orphanet:110	Bardet-Biedl syndrome
BBS1	Orphanet:791	Retinitis pigmentosa

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
ZDHHC24	HGNC:27387	ENSG00000174165	Q6UX98	Probable palmitoyltransferase ZDHHC24	clinvar
BBS1	HGNC:966	ENSG00000174483	Q8NFJ9	BBSome complex member BBS1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZDHHC24	Probable palmitoyltransferase ZDHHC24	Probable palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates.
BBS1	BBSome complex member BBS1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

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)
ZDHHC24	Other/Unknown	no		Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like
BBS1	Other/Unknown	no		Quinoprotein_ADH-like_sf, BBS1, BBS1_N

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
parotid gland	1
triceps brachii	1
left ovary	1
ovary	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZDHHC24	232	ubiquitous	marker	parotid gland, diaphragm, triceps brachii
BBS1	134	ubiquitous	yes	right uterine tube, left ovary, ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS1	2,189
ZDHHC24	567

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BBS1	Q8NFJ9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZDHHC24	Q6UX98	89.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.008	BBS1
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	BBS1
Cilium Assembly	1	108.8×	0.012	BBS1
Organelle biogenesis and maintenance	1	66.0×	0.015	BBS1

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
photoreceptor cell morphogenesis	1	1404.3×	0.010	BBS1
olfactory behavior	1	936.2×	0.010	BBS1
regulation of cilium beat frequency involved in ciliary motility	1	936.2×	0.010	BBS1
striatum development	1	561.7×	0.010	BBS1
hormone metabolic process	1	443.5×	0.010	BBS1
ventricular system development	1	421.3×	0.010	BBS1
brain morphogenesis	1	366.4×	0.010	BBS1
neural precursor cell proliferation	1	337.0×	0.010	BBS1
Golgi to plasma membrane protein transport	1	263.3×	0.012	BBS1
adult behavior	1	234.1×	0.012	BBS1
protein localization to cilium	1	200.6×	0.012	BBS1
dendrite development	1	195.9×	0.012	BBS1
photoreceptor cell maintenance	1	179.3×	0.012	BBS1
fertilization	1	156.0×	0.012	BBS1
protein targeting to membrane	1	147.8×	0.012	ZDHHC24
non-motile cilium assembly	1	145.3×	0.012	BBS1
retina development in camera-type eye	1	127.7×	0.012	BBS1
cartilage development	1	125.8×	0.012	BBS1
hippocampus development	1	115.4×	0.013	BBS1
cerebral cortex development	1	102.8×	0.014	BBS1
fat cell differentiation	1	90.6×	0.015	BBS1
response to endoplasmic reticulum stress	1	83.4×	0.015	BBS1
sensory perception of smell	1	78.0×	0.016	BBS1
neuron migration	1	66.9×	0.017	BBS1
microtubule cytoskeleton organization	1	60.6×	0.018	BBS1
lipid metabolic process	1	45.8×	0.023	BBS1
visual perception	1	39.8×	0.026	BBS1
cilium assembly	1	36.8×	0.027	BBS1

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
ZDHHC24	0	0
BBS1	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	ZDHHC24, BBS1

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)
ZDHHC24	0	—
BBS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.