Bardet-biedl syndrome 21

Summary

Bardet-biedl syndrome 21 (MONDO:0044308) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bardet-biedl syndrome 21
Mondo ID	MONDO:0044308
OMIM	617406
DOID	DOID:0081010
UMLS	C4319932
MedGen	1374358
GARD	0016226
Is cancer (heuristic)	no

Also known as: BBS21

Data availability: 27 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bardet-Biedl syndrome › bardet-biedl syndrome 21

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 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

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

27 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 benign/likely benign, 2 pathogenic, 2 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070350	NM_177965.4(CFAP418):c.177del (p.Glu60fs)	CFAP418	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31194	NM_177965.4(CFAP418):c.529C>T (p.Arg177Trp)	CFAP418	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
417789	NM_177965.4(CFAP418):c.304A>T (p.Lys102Ter)	CFAP418	Pathogenic	no assertion criteria provided
1179152	NM_177965.4(CFAP418):c.124del (p.Arg42fs)	LOC130000784	Pathogenic	criteria provided, single submitter
684431	NM_177965.4(CFAP418):c.240del (p.Ser81fs)	CFAP418	Likely pathogenic	criteria provided, single submitter
684432	NM_177965.4(CFAP418):c.130C>T (p.Gln44Ter)	CFAP418	Likely pathogenic	criteria provided, single submitter
1045329	NM_177965.4(CFAP418):c.155+12G>A	CFAP418	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1681122	NM_177965.4(CFAP418):c.414G>A (p.Leu138=)	CFAP418	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1055937	NM_177965.4(CFAP418):c.395G>A (p.Cys132Tyr)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681114	NM_177965.4(CFAP418):c.602G>C (p.Arg201Pro)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681116	NM_177965.4(CFAP418):c.556A>G (p.Arg186Gly)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681117	NM_177965.4(CFAP418):c.530G>A (p.Arg177Gln)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681120	NM_177965.4(CFAP418):c.449C>G (p.Ser150Trp)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681121	NM_177965.4(CFAP418):c.422G>A (p.Ser141Asn)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681128	NM_177965.4(CFAP418):c.331G>A (p.Gly111Arg)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681133	NM_177965.4(CFAP418):c.254C>T (p.Ser85Phe)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681153	NM_177965.4(CFAP418):c.82G>A (p.Glu28Lys)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
3893021	NM_177965.4(CFAP418):c.130C>G (p.Gln44Glu)	CFAP418	Uncertain significance	criteria provided, single submitter
430653	NM_177965.4(CFAP418):c.533C>T (p.Ala178Val)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
939845	NM_177965.4(CFAP418):c.317C>T (p.Pro106Leu)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
957321	NM_177965.4(CFAP418):c.194G>T (p.Ser65Ile)	CFAP418	Uncertain significance	criteria provided, multiple submitters, no conflicts
1681154	NM_177965.4(CFAP418):c.65T>C (p.Leu22Pro)	CFAP418-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1047519	NM_177965.4(CFAP418):c.43A>G (p.Lys15Glu)	LOC130000784	Uncertain significance	criteria provided, multiple submitters, no conflicts
953986	NM_177965.4(CFAP418):c.134C>G (p.Ala45Gly)	LOC130000784	Uncertain significance	criteria provided, multiple submitters, no conflicts
1167428	NM_177965.4(CFAP418):c.243+20T>C	CFAP418	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1681125	NM_177965.4(CFAP418):c.375-16T>A	CFAP418	Likely benign	criteria provided, multiple submitters, no conflicts
1681144	NM_177965.4(CFAP418):c.155+20T>G	LOC130000784	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 3 · 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
CFAP418	Limited	Autosomal recessive	bardet-biedl syndrome 21	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFAP418	Orphanet:110	Bardet-Biedl syndrome
CFAP418	Orphanet:1872	Cone rod dystrophy
CFAP418	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFAP418	HGNC:27232	ENSG00000156172	Q96NL8	Cilia- and flagella-associated protein 418	gencc,clinvar
CFAP418-AS1	HGNC:50444	ENSG00000253773		CFAP418 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFAP418	Cilia- and flagella-associated protein 418	May be involved in photoreceptor outer segment disk morphogenesis.

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)
CFAP418	Other/Unknown	no		CFAP418
CFAP418-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

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
buccal mucosa cell	1
oviduct epithelium	1
secondary oocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory segment of nasal mucosa	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFAP418	201	ubiquitous	yes	secondary oocyte, oviduct epithelium, buccal mucosa cell
CFAP418-AS1	127	broad	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFAP418	635
CFAP418-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFAP418	Q96NL8	75.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
photoreceptor cell morphogenesis	1	2808.7×	4e-04	CFAP418

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
CFAP418	0	0
CFAP418-AS1	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	2	CFAP418, CFAP418-AS1

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)
CFAP418	0	—
CFAP418-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.