Bardet-Biedl syndrome 20

Summary

Bardet-Biedl syndrome 20 (MONDO:0023670) is a disease caused by IFT172 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: IFT172 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 441

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 20
Mondo ID	MONDO:0023670
OMIM	619471
DOID	DOID:0081009
UMLS	C4310707
MedGen	934674
GARD	0025375
Is cancer (heuristic)	no

Also known as: BBS20

Data availability: 441 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 20

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 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

441 retrieved; paginated sample, class counts are floors:

271 uncertain significance, 66 conflicting classifications of pathogenicity, 45 likely benign, 24 likely pathogenic, 19 pathogenic/likely pathogenic, 13 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068458	NM_015662.3(IFT172):c.3793G>T (p.Glu1265Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075988	NM_015662.3(IFT172):c.2646C>A (p.Cys882Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1189092	NM_015662.3(IFT172):c.4428+3A>G	IFT172	Pathogenic	no assertion criteria provided
1355657	NM_015662.3(IFT172):c.1078del (p.Glu359_Val360insTer)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1394651	NM_015662.3(IFT172):c.4519C>T (p.Arg1507Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455123	NM_015662.3(IFT172):c.5044C>T (p.Arg1682Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456416	NM_015662.3(IFT172):c.2536C>T (p.Arg846Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191366	NM_015662.3(IFT172):c.4701C>A (p.His1567Gln)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191367	NM_015662.3(IFT172):c.1525-1G>A	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2019892	NM_015662.3(IFT172):c.1871_1872del (p.Thr624fs)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2083818	NM_015662.3(IFT172):c.455_462dup (p.Val155fs)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208589	NM_015662.3(IFT172):c.112C>T (p.Arg38Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2172085	NM_015662.3(IFT172):c.2584dup (p.Asp862fs)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2941237	NM_015662.3(IFT172):c.978dup (p.Glu327Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3586326	NM_015662.3(IFT172):c.2456_2457del (p.Leu818_Phe819insTer)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446697	NM_015662.3(IFT172):c.2765dup (p.Tyr922Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
816981	NM_015662.3(IFT172):c.2365C>T (p.Arg789Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
97022	NM_015662.3(IFT172):c.5179T>C (p.Cys1727Arg)	IFT172	Pathogenic	criteria provided, multiple submitters, no conflicts
97023	NM_015662.3(IFT172):c.4925_4928del (p.Arg1642fs)	IFT172	Pathogenic	criteria provided, multiple submitters, no conflicts
97024	NM_015662.3(IFT172):c.4630C>T (p.Arg1544Cys)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
97032	NM_015662.3(IFT172):c.2158del (p.Arg720fs)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073662	NM_015662.3(IFT172):c.4789dup (p.Leu1597fs)	KRTCAP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1487038	NM_015662.3(IFT172):c.402+2T>G	IFT172	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2125286	NM_015662.3(IFT172):c.4914+1G>A	IFT172	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2303199	NM_015662.3(IFT172):c.2976-2A>T	IFT172	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2927923	NM_015662.3(IFT172):c.1411+2T>C	IFT172	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3572962	NM_015662.3(IFT172):c.3397dup (p.Ser1133fs)	IFT172	Likely pathogenic	criteria provided, single submitter
3586287	NM_015662.3(IFT172):c.4280G>A (p.Trp1427Ter)	IFT172	Likely pathogenic	criteria provided, single submitter
3586289	NM_015662.3(IFT172):c.4224+1G>A	IFT172	Likely pathogenic	criteria provided, single submitter
3586293	NM_015662.3(IFT172):c.3880del (p.Arg1294fs)	IFT172	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
IFT172	Strong	Autosomal recessive	Bardet-Biedl syndrome 20	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	gencc,clinvar
KRTCAP3	HGNC:28943	ENSG00000157992	Q53RY4	Keratinocyte-associated protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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)
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
KRTCAP3	Other/Unknown	no		Beta-casein-like

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
right uterine tube	2
bronchial epithelial cell	1
left testis	1
mucosa of transverse colon	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT172	236	ubiquitous	marker	right uterine tube, bronchial epithelial cell, left testis
KRTCAP3	197	broad	marker	mucosa of transverse colon, pancreatic ductal cell, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT172	1,922
KRTCAP3	639

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
KRTCAP3	Q53RY4	76.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Intraflagellar transport	1	200.3×	0.006	IFT172
Hedgehog ‘off’ state	1	178.4×	0.006	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hindgut development	1	16852.0×	0.001	IFT172
left/right axis specification	1	1203.7×	0.005	IFT172
embryonic camera-type eye morphogenesis	1	1123.5×	0.005	IFT172
spinal cord motor neuron differentiation	1	936.2×	0.005	IFT172
intraciliary anterograde transport	1	887.0×	0.005	IFT172
negative regulation of keratinocyte proliferation	1	702.2×	0.005	IFT172
keratinocyte proliferation	1	581.1×	0.005	IFT172
intraciliary transport	1	561.7×	0.005	IFT172
negative regulation of smoothened signaling pathway	1	455.5×	0.005	IFT172
dorsal/ventral pattern formation	1	421.3×	0.005	IFT172
positive regulation of smoothened signaling pathway	1	421.3×	0.005	IFT172
limb development	1	411.0×	0.005	IFT172
cytoplasmic microtubule organization	1	343.9×	0.005	IFT172
non-motile cilium assembly	1	290.6×	0.006	IFT172
bone development	1	276.3×	0.006	IFT172
heart looping	1	267.5×	0.006	IFT172
roof of mouth development	1	247.8×	0.006	IFT172
epidermis development	1	210.7×	0.006	IFT172
neural tube closure	1	187.2×	0.007	IFT172
smoothened signaling pathway	1	181.2×	0.007	IFT172
protein processing	1	170.2×	0.007	IFT172
Notch signaling pathway	1	141.6×	0.008	IFT172
brain development	1	79.5×	0.013	IFT172
cilium assembly	1	73.6×	0.014	IFT172

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
IFT172	0	0
KRTCAP3	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	IFT172, KRTCAP3

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)
IFT172	0	—
KRTCAP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.