Bardet-Biedl syndrome 19

Summary

Bardet-Biedl syndrome 19 (MONDO:0014447) is a disease caused by IFT27 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: IFT27 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 19
Mondo ID	MONDO:0014447
OMIM	615996
DOID	DOID:0110141
UMLS	C3889475
MedGen	855173
GARD	0016043
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 19 · Bardet-Biedl syndrome caused by mutation in IFT27 · Bardet-Biedl syndrome type 19 · BBS19 · IFT27 Bardet-Biedl syndrome

Data availability: 8 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 19

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 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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
140462	NM_001177701.3(IFT27):c.299G>A (p.Cys100Tyr)	CACNG2-DT	Pathogenic	criteria provided, single submitter
585274	NM_001177701.3(IFT27):c.352+1G>T	CACNG2-DT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2111398	NM_001177701.3(IFT27):c.97C>T (p.Gln33Ter)	IFT27	Pathogenic	criteria provided, single submitter
585273	NM_001177701.3(IFT27):c.107A>G (p.Tyr36Cys)	IFT27	Pathogenic	criteria provided, multiple submitters, no conflicts
1319939	NM_001177701.3(IFT27):c.197C>A (p.Ala66Asp)	LOC126863139	Likely pathogenic	no assertion criteria provided
1438203	NM_001177701.3(IFT27):c.136G>T (p.Val46Leu)	IFT27	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992407	NM_001177701.3(IFT27):c.116C>G (p.Thr39Arg)	IFT27	Uncertain significance	no assertion criteria provided
1285253	NM_001177701.3(IFT27):c.174+21G>A	IFT27	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
IFT27	Strong	Autosomal recessive	Bardet-Biedl syndrome 19	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT27	Orphanet:110	Bardet-Biedl syndrome

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
IFT27	HGNC:18626	ENSG00000100360	Q9BW83	Intraflagellar transport protein 27 homolog	gencc,clinvar
CACNG2-DT	HGNC:55682	ENSG00000234688		CACNG2 divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT27	Intraflagellar transport protein 27 homolog	Small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6.

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)
IFT27	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
CACNG2-DT	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	1
cerebellar cortex	1
cerebellum	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT27	251	ubiquitous	marker	right uterine tube, epithelium of bronchus, bronchial epithelial cell
CACNG2-DT	71		yes	right hemisphere of cerebellum, cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT27	1,040
CACNG2-DT	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT27	Q9BW83	92.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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×	0.005	IFT27

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
intraciliary anterograde transport	1	887.0×	0.005	IFT27
inner ear receptor cell stereocilium organization	1	842.6×	0.005	IFT27
intraciliary transport	1	561.7×	0.005	IFT27
cochlea development	1	468.1×	0.005	IFT27
smoothened signaling pathway	1	181.2×	0.011	IFT27
kidney development	1	140.4×	0.012	IFT27
vesicle-mediated transport	1	96.3×	0.015	IFT27
cilium assembly	1	73.6×	0.017	IFT27
intracellular protein transport	1	64.8×	0.017	IFT27
spermatogenesis	1	35.2×	0.028	IFT27

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
IFT27	0	0
CACNG2-DT	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	IFT27, CACNG2-DT

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)
IFT27	0	—
CACNG2-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.