Bardet-Biedl syndrome 4

Summary

Bardet-Biedl syndrome 4 (MONDO:0014433) is a disease caused by BBS4 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BBS4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 275

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 4
Mondo ID	MONDO:0014433
MeSH	C537912
OMIM	615982
DOID	DOID:0110126
UMLS	C2936864
MedGen	423627
GARD	0000823
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 4 · Bardet-Biedl syndrome type 4 · BBS4

Data availability: 275 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 4

Related subtypes (21): Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 3, Bardet-Biedl syndrome 6, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome 5, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome 9, 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

275 retrieved; paginated sample, class counts are floors:

118 uncertain significance, 54 likely pathogenic, 32 pathogenic/likely pathogenic, 24 conflicting classifications of pathogenicity, 16 likely benign, 14 pathogenic, 13 benign, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012856	NM_033028.5(BBS4):c.332+2_332+3insTT	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068712	NM_033028.5(BBS4):c.1248+2T>C	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075982	NM_033028.5(BBS4):c.929del (p.Leu310fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172704	NM_033028.5(BBS4):c.187C>T (p.Gln63Ter)	BBS4	Pathogenic	criteria provided, multiple submitters, no conflicts
1179101	NM_033028.5(BBS4):c.1375C>T (p.Gln459Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179106	NM_033028.5(BBS4):c.1318_1321del (p.Val440fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1209985	NM_033028.5(BBS4):c.777_778del (p.Tyr259_Arg260delinsTer)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324345	NM_033028.5(BBS4):c.1311_1312insT (p.Lys438Ter)	BBS4	Pathogenic	criteria provided, single submitter
1700584	NM_033028.5(BBS4):c.220G>A (p.Ala74Thr)	BBS4	Pathogenic	criteria provided, single submitter
1964049	NM_033028.5(BBS4):c.67C>T (p.Gln23Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2014919	NM_033028.5(BBS4):c.1248+1G>A	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2058675	NM_033028.5(BBS4):c.76+2T>C	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2099641	NM_033028.5(BBS4):c.1294dup (p.Glu432fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137734	NM_033028.5(BBS4):c.1180C>T (p.Gln394Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21730	NM_033028.5(BBS4):c.406-2A>C	BBS4	Pathogenic	criteria provided, single submitter
217435	NM_033028.5(BBS4):c.406-2A>G	BBS4	Pathogenic	no assertion criteria provided
2185519	NM_033028.5(BBS4):c.1264C>T (p.Gln422Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2192610	NM_033028.5(BBS4):c.616dup (p.Thr206fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2197130	NM_033028.5(BBS4):c.10G>T (p.Glu4Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2198631	NM_033028.5(BBS4):c.220+1G>A	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2200217	NM_033028.5(BBS4):c.514dup (p.Ile172fs)	BBS4	Pathogenic	criteria provided, multiple submitters, no conflicts
236484	NM_033028.5(BBS4):c.712-1G>A	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
266087	NM_033028.5(BBS4):c.1226del (p.Ser409fs)	BBS4	Pathogenic	criteria provided, multiple submitters, no conflicts
266089	NM_033028.5(BBS4):c.172C>T (p.Gln58Ter)	BBS4	Pathogenic	criteria provided, single submitter
2680035	NM_033028.5(BBS4):c.406G>T (p.Glu136Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680037	NM_033028.5(BBS4):c.642+2T>G	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680040	NM_033028.5(BBS4):c.55C>T (p.Gln19Ter)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680041	NM_033028.5(BBS4):c.1389dup (p.Ser464fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680049	NM_033028.5(BBS4):c.87del (p.Pro30fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680052	NM_033028.5(BBS4):c.276_277del (p.Ala94fs)	BBS4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
BBS4	Definitive	Autosomal recessive	Bardet-Biedl syndrome 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS4	Orphanet:110	Bardet-Biedl 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
BBS4	HGNC:969	ENSG00000140463	Q96RK4	BBSome complex member BBS4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS4	BBSome complex member BBS4	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: 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)
BBS4	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt

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
oocyte	1
right uterine tube	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS4	278	ubiquitous	marker	right uterine tube, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS4	2,544

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BBS4	Q96RK4	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.008	BBS4
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	BBS4
Cilium Assembly	1	108.8×	0.012	BBS4
Organelle biogenesis and maintenance	1	66.0×	0.015	BBS4

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
regulation of non-motile cilium assembly	1	16852.0×	0.003	BBS4
sensory processing	1	5617.3×	0.003	BBS4
negative regulation of appetite by leptin-mediated signaling pathway	1	4213.0×	0.003	BBS4
protein localization to photoreceptor outer segment	1	2407.4×	0.003	BBS4
regulation of cilium beat frequency involved in ciliary motility	1	1872.4×	0.003	BBS4
retinal rod cell development	1	1685.2×	0.003	BBS4
fat pad development	1	1685.2×	0.003	BBS4
microtubule anchoring at centrosome	1	1404.3×	0.003	BBS4
erythrocyte homeostasis	1	1296.3×	0.003	BBS4
retina homeostasis	1	1123.5×	0.003	BBS4
striatum development	1	1123.5×	0.003	BBS4
maintenance of protein location in nucleus	1	1123.5×	0.003	BBS4
negative regulation of systemic arterial blood pressure	1	1053.2×	0.003	BBS4
photoreceptor cell outer segment organization	1	1053.2×	0.003	BBS4
regulation of stress fiber assembly	1	991.3×	0.003	BBS4
negative regulation of actin filament polymerization	1	936.2×	0.003	BBS4
ventricular system development	1	842.6×	0.003	BBS4
face development	1	802.5×	0.003	BBS4
melanosome transport	1	766.0×	0.003	BBS4
positive regulation of cilium assembly	1	766.0×	0.003	BBS4
brain morphogenesis	1	732.7×	0.003	BBS4
protein localization to centrosome	1	674.1×	0.003	BBS4
sperm flagellum assembly	1	674.1×	0.003	BBS4
B cell homeostasis	1	561.7×	0.004	BBS4
positive regulation of multicellular organism growth	1	495.6×	0.004	BBS4
adult behavior	1	468.1×	0.004	BBS4
regulation of lipid metabolic process	1	432.1×	0.004	BBS4
regulation of cytokinesis	1	421.3×	0.004	BBS4
protein localization to cilium	1	401.2×	0.004	BBS4
dendrite development	1	391.9×	0.004	BBS4

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
BBS4	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	BBS4

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)
BBS4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.