Bardet-Biedl syndrome 22

Summary

Bardet-Biedl syndrome 22 (MONDO:0014926) is a disease caused by IFT74 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: IFT74 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 22
Mondo ID	MONDO:0014926
OMIM	617119
DOID	DOID:0081011
UMLS	C5561936
MedGen	1794146
GARD	0016193
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 20; BBS20 · Bardet-Biedl syndrome caused by mutation in IFT74 · Bardet-Biedl syndrome type 20 · BBS20 · IFT74 Bardet-Biedl syndrome

Data availability: 16 ClinVar variants · 2 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 22

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 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

16 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 3 benign, 3 pathogenic/likely pathogenic, 2 pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1192529	NM_025103.4(IFT74):c.371_372del (p.Gln124fs)	IFT74	Pathogenic	no assertion criteria provided
1925311	NM_025103.4(IFT74):c.358G>T (p.Glu120Ter)	IFT74	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254276	NM_025103.4(IFT74):c.1685-1G>T	IFT74	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4082009	NM_025103.4(IFT74):c.727G>T (p.Glu243Ter)	IFT74	Pathogenic	no assertion criteria provided
431748	GRCh38/hg38 9p21.2(chr9:27040565-27060992)	IFT74	Pathogenic/Likely pathogenic	no assertion criteria provided
3068540	NM_025103.4(IFT74):c.909dup (p.Glu304fs)	IFT74	Likely pathogenic	no assertion criteria provided
684551	NM_025103.4(IFT74):c.163A>T (p.Ile55Leu)	IFT74	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
849763	NM_015662.3(IFT172):c.1478T>G (p.Leu493Arg)	IFT172	Uncertain significance	criteria provided, multiple submitters, no conflicts
869114	NM_015662.3(IFT172):c.2155C>T (p.His719Tyr)	IFT172	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028870	NM_025103.4(IFT74):c.94T>C (p.Ser32Pro)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
2170750	NM_025103.4(IFT74):c.1343G>A (p.Arg448His)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
2267201	NM_025103.4(IFT74):c.1492A>G (p.Ile498Val)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242550	NM_025103.4(IFT74):c.1624-1G>A	IFT74	Uncertain significance	criteria provided, single submitter
1246135	NM_025103.4(IFT74):c.1790C>T (p.Thr597Ile)	IFT74	Benign	criteria provided, multiple submitters, no conflicts
1247882	NM_025103.4(IFT74):c.165A>G (p.Ile55Met)	IFT74	Benign	criteria provided, multiple submitters, no conflicts
1265179	NM_025103.4(IFT74):c.254A>G (p.Lys85Arg)	IFT74	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 7 · 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
IFT74	Definitive	Autosomal recessive	Bardet-Biedl syndrome 22	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT74	Orphanet:110	Bardet-Biedl syndrome
IFT74	Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa
IFT74	Orphanet:475	Isolated Joubert syndrome
IFT172	Orphanet:110	Bardet-Biedl syndrome
IFT172	Orphanet:140969	Saldino-Mainzer syndrome
IFT172	Orphanet:474	Jeune syndrome
IFT172	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
IFT74	HGNC:21424	ENSG00000096872	Q96LB3	Intraflagellar transport protein 74 homolog	gencc,clinvar
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT74	Intraflagellar transport protein 74 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.
IFT172	Intraflagellar transport protein 172 homolog	Required for the maintenance and formation of cilia.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFT74	Other/Unknown	no		IFT74
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
bronchial epithelial cell	2
right uterine tube	2
caput epididymis	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT74	272	ubiquitous	marker	bronchial epithelial cell, caput epididymis, right uterine tube
IFT172	236	ubiquitous	marker	right uterine tube, bronchial epithelial cell, left testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT74	1,937
IFT172	1,922

Intra-cohort edges

A	B	Sources
IFT172	IFT74	biogrid_interaction, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFT172	Q9UG01	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT74	Q96LB3	81.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Intraflagellar transport	2	200.3×	5e-05	IFT74, IFT172
Hedgehog ‘off’ state	1	89.2×	0.011	IFT172

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
intraciliary anterograde transport	2	887.0×	3e-05	IFT74, IFT172
negative regulation of keratinocyte proliferation	2	702.2×	3e-05	IFT74, IFT172
keratinocyte proliferation	2	581.1×	3e-05	IFT74, IFT172
non-motile cilium assembly	2	290.6×	9e-05	IFT74, IFT172
Notch signaling pathway	2	141.6×	3e-04	IFT74, IFT172
hindgut development	1	8426.0×	6e-04	IFT172
cilium assembly	2	73.6×	8e-04	IFT74, IFT172
intraciliary transport involved in cilium assembly	1	1203.7×	0.003	IFT74
keratinocyte development	1	766.0×	0.004	IFT74
left/right axis specification	1	601.9×	0.005	IFT172
embryonic camera-type eye morphogenesis	1	561.7×	0.005	IFT172
positive regulation of cell adhesion mediated by integrin	1	526.6×	0.005	IFT74
spinal cord motor neuron differentiation	1	468.1×	0.005	IFT172
intraciliary transport	1	280.9×	0.008	IFT172
negative regulation of smoothened signaling pathway	1	227.7×	0.008	IFT172
dorsal/ventral pattern formation	1	210.7×	0.008	IFT172
positive regulation of smoothened signaling pathway	1	210.7×	0.008	IFT172
limb development	1	205.5×	0.008	IFT172
cytoplasmic microtubule organization	1	172.0×	0.009	IFT172
bone development	1	138.1×	0.011	IFT172
heart looping	1	133.8×	0.011	IFT172
determination of left/right symmetry	1	127.7×	0.011	IFT74
roof of mouth development	1	123.9×	0.011	IFT172
epidermis development	1	105.3×	0.012	IFT172
neural tube closure	1	93.6×	0.013	IFT172
smoothened signaling pathway	1	90.6×	0.013	IFT172
protein processing	1	85.1×	0.013	IFT172
brain development	1	39.8×	0.026	IFT172
heart development	1	39.4×	0.026	IFT74
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	IFT74

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
IFT74	0	0
IFT172	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	IFT74, IFT172

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)
IFT74	0	—
IFT172	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.