Bardet-Biedl syndrome 3

Summary

Bardet-Biedl syndrome 3 (MONDO:0010832) is a disease caused by ARL6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ARL6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 239

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 3
Mondo ID	MONDO:0010832
MeSH	C537911
OMIM	600151
DOID	DOID:0110125
UMLS	C1859564
MedGen	347179
GARD	0000822
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 3 · Bardet-Biedl syndrome type 3 · BBS3

Data availability: 239 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 3

Related subtypes (21): Bardet-Biedl syndrome 1, 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 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

239 retrieved; paginated sample, class counts are floors:

105 likely benign, 78 uncertain significance, 23 pathogenic, 14 likely pathogenic, 8 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 3 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028925	NM_001278293.3(ARL6):c.228C>G (p.Tyr76Ter)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075539	NM_001278293.3(ARL6):c.4G>T (p.Gly2Ter)	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
1076146	NC_000003.11:g.(?97194196)(97510809_?)del	ARL6	Pathogenic	criteria provided, single submitter
1446585	NM_001278293.3(ARL6):c.1A>G (p.Met1Val)	ARL6	Pathogenic	criteria provided, single submitter
1457182	NC_000003.11:g.(?97498983)(97516893_?)del	ARL6	Pathogenic	criteria provided, single submitter
1459992	NC_000003.11:g.(?97486952)(97516893_?)del	ARL6	Pathogenic	criteria provided, single submitter
1805423	NM_001278293.3(ARL6):c.534A>G (p.Gln178=)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2040	NM_001278293.3(ARL6):c.364C>T (p.Arg122Ter)	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
2041	NM_001278293.3(ARL6):c.506G>C (p.Gly169Ala)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2042	NM_001278293.3(ARL6):c.92C>T (p.Thr31Met)	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
2043	NM_001278293.3(ARL6):c.509T>G (p.Leu170Trp)	ARL6	Pathogenic	no assertion criteria provided
2044	NM_001278293.3(ARL6):c.92C>G (p.Thr31Arg)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2071999	NM_001278293.3(ARL6):c.469del (p.Trp157fs)	ARL6	Pathogenic	criteria provided, single submitter
2102573	NM_001278293.3(ARL6):c.262C>T (p.Gln88Ter)	ARL6	Pathogenic	criteria provided, single submitter
2115026	NM_001278293.3(ARL6):c.127C>T (p.Gln43Ter)	ARL6	Pathogenic	criteria provided, single submitter
2920654	NM_001278293.3(ARL6):c.377T>G (p.Leu126Ter)	ARL6	Pathogenic	no assertion criteria provided
2940871	NM_001278293.3(ARL6):c.228C>A (p.Tyr76Ter)	ARL6	Pathogenic	criteria provided, single submitter
2942834	NM_001278293.3(ARL6):c.406_409del (p.Asp136fs)	ARL6	Pathogenic	criteria provided, single submitter
2943163	NM_001278293.3(ARL6):c.188T>A (p.Leu63Ter)	ARL6	Pathogenic	criteria provided, single submitter
2950730	NM_001278293.3(ARL6):c.66C>A (p.Cys22Ter)	ARL6	Pathogenic	criteria provided, single submitter
2950809	NM_001278293.3(ARL6):c.252T>G (p.Tyr84Ter)	ARL6	Pathogenic	criteria provided, single submitter
3246908	NC_000003.11:g.(?97486952)(97487094_?)del	ARL6	Pathogenic	criteria provided, single submitter
370033	NM_001278293.3(ARL6):c.351_353delinsGAAAA (p.Asp117fs)	ARL6	Pathogenic	no assertion criteria provided
438186	NM_001278293.3(ARL6):c.281T>C (p.Ile94Thr)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
576069	NM_001278293.3(ARL6):c.185+1G>C	ARL6	Pathogenic	criteria provided, multiple submitters, no conflicts
68064	NM_001278293.3(ARL6):c.272T>C (p.Ile91Thr)	ARL6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
832088	NC_000003.12:g.(?97768108)(97768230_?)del	ARL6	Pathogenic	criteria provided, single submitter
861499	NM_001278293.3(ARL6):c.506del (p.Gly169fs)	ARL6	Pathogenic	criteria provided, single submitter
977510	NM_001278293.3(ARL6):c.373dup (p.Ile125fs)	ARL6	Pathogenic	criteria provided, single submitter
1180769	NM_001278293.3(ARL6):c.349+1G>A	ARL6	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
ARL6	Definitive	Autosomal recessive	Bardet-Biedl syndrome 3	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARL6	Orphanet:110	Bardet-Biedl syndrome
ARL6	Orphanet:791	Retinitis pigmentosa

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
ARL6	HGNC:13210	ENSG00000113966	Q9H0F7	ADP-ribosylation factor-like protein 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARL6	ADP-ribosylation factor-like protein 6	Involved in membrane protein trafficking at the base of the ciliary organelle.

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)
ARL6	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF

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
Brodmann (1909) area 23	1
endothelial cell	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARL6	228	ubiquitous	marker	oviduct epithelium, Brodmann (1909) area 23, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARL6	1,811

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARL6	Q9H0F7	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	ARL6
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	ARL6
Cilium Assembly	1	108.8×	0.012	ARL6
Organelle biogenesis and maintenance	1	66.0×	0.015	ARL6

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
protein transport from ciliary membrane to plasma membrane	1	5617.3×	0.002	ARL6
protein localization to non-motile cilium	1	4213.0×	0.002	ARL6
protein polymerization	1	991.3×	0.004	ARL6
melanosome transport	1	766.0×	0.004	ARL6
retina layer formation	1	648.1×	0.004	ARL6
regulation of smoothened signaling pathway	1	624.1×	0.004	ARL6
protein localization to cilium	1	401.2×	0.006	ARL6
protein targeting to membrane	1	295.6×	0.007	ARL6
determination of left/right symmetry	1	255.3×	0.007	ARL6
fat cell differentiation	1	181.2×	0.009	ARL6
Wnt signaling pathway	1	99.7×	0.014	ARL6
vesicle-mediated transport	1	96.3×	0.014	ARL6
brain development	1	79.5×	0.014	ARL6
visual perception	1	79.5×	0.014	ARL6
cilium assembly	1	73.6×	0.014	ARL6
intracellular protein transport	1	64.8×	0.015	ARL6

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
ARL6	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	ARL6

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)
ARL6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.