BBS1 - dismech genes

Normal function · from ai-gene-review (Q8NFJ9, commit 79fe13b38970) · AI-generated, not KB evidence

BBS1 (Bardet-Biedl syndrome 1 protein) is a core subunit of the BBSome, an octameric, coat-like protein complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP1/BBIP10) that is structurally related to COPI, COPII and clathrin coats. The BBSome acts as a cargo adaptor that sorts specific transmembrane proteins, notably ciliary G-protein-coupled receptors and Hedgehog-pathway components such as Smoothened, into and out of the primary cilium by coupling them to intraflagellar transport. BBS1 contributes a seven-bladed beta-propeller that provides a principal cargo-recognition surface and binds the GTP-loaded Arf-like GTPase ARL6/BBS3, which recruits the BBSome to the ciliary membrane. The BBSome cooperates with the Rab8 guanine-nucleotide exchange factor RAB3IP/Rabin8 to promote ciliary membrane biogenesis. BBS1 is predominantly found at the ciliary membrane and in the cytoplasm, with pools at the centrosome/basal body and centriolar satellites. Loss of BBS1 function causes Bardet-Biedl syndrome, an autosomal recessive ciliopathy featuring retinal degeneration, obesity, polydactyly, renal malformation, hypogenitalism and intellectual disability; BBS1 is the most commonly mutated BBS gene, with M390R the most frequent allele.

BBS1 is a constitutive core subunit of the BBSome, an octameric coat-like complex that assembles in the cytoplasm and acts at the ciliary membrane to sort transmembrane cargo to and from the primary cilium.

BBS1 mediates membrane targeting of the BBSome by binding the GTP-loaded small GTPase ARL6/BBS3 through its beta-propeller, recruiting the cargo-laden coat to the ciliary membrane.

molecular function: small GTPase binding

As part of the BBSome, BBS1 drives localization of membrane proteins (ciliary GPCRs such as SSTR3, Hedgehog component Smoothened, leptin receptor, polycystin-1) to and from the cilium, coupling cargo recognition to intraflagellar transport.

BBS1/BBSome is required for assembly and maintenance of non-motile (primary/sensory) cilia, including the photoreceptor connecting cilium; loss of BBS1 disrupts ciliogenesis and ciliary cargo homeostasis.

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Bardet-Biedl syndrome	untyped Pathogenic biallelic variants	mechanism: BBSome subunit deficiency; Pathogenic BBS gene defects
BBSome-related retinitis pigmentosa	untyped Pathogenic biallelic variants at the mild end of the BBS1 allelic spectrum	mechanism: Partial or retina-selective BBSome dysfunction subtype: BBS1 isolated RP scoped to subtype: BBS1 isolated RP

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
BBS1-related ciliopathy MONDO:1040043	AR	Definitive 2023-12-07	no dismech entry

Mechanism modules · computed from kb/

bbsome_trafficking via Bardet-Biedl syndrome, BBSome-related retinitis pigmentosa