Bardet-Biedl syndrome 17

Summary

Bardet-Biedl syndrome 17 (MONDO:0014445) is a disease caused by LZTFL1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: LZTFL1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 17
Mondo ID	MONDO:0014445
OMIM	615994
DOID	DOID:0110139
UMLS	C3714980
MedGen	811538
GARD	0016041
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 17 · Bardet-Biedl syndrome caused by mutation in LZTFL1 · Bardet-Biedl syndrome type 17 · BBS17 · LZTFL1 Bardet-Biedl syndrome

Data availability: 50 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 17

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 18, Bardet-Biedl syndrome 19, 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

50 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 6 benign/likely benign, 5 likely pathogenic, 4 pathogenic, 3 conflicting classifications of pathogenicity, 2 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
126380	NM_020347.4(LZTFL1):c.260T>C (p.Leu87Pro)	LZTFL1	Pathogenic	no assertion criteria provided
126381	NM_020347.4(LZTFL1):c.778G>T (p.Glu260Ter)	LZTFL1	Pathogenic	no assertion criteria provided
2573036	NM_020347.4(LZTFL1):c.253C>T (p.Arg85Ter)	LZTFL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3234009	NM_020347.4(LZTFL1):c.505A>T (p.Lys169Ter)	LZTFL1	Pathogenic	no assertion criteria provided
39770	NM_020347.4(LZTFL1):c.402_406del (p.Pro136fs)	LZTFL1	Pathogenic	no assertion criteria provided
1333226	NM_020347.4(LZTFL1):c.457-1G>T	LZTFL1	Likely pathogenic	criteria provided, single submitter
3589175	NM_020347.4(LZTFL1):c.745_746del (p.Arg249fs)	LZTFL1	Likely pathogenic	criteria provided, single submitter
3589184	NM_020347.4(LZTFL1):c.523-1G>A	LZTFL1	Likely pathogenic	criteria provided, single submitter
3589189	NM_020347.4(LZTFL1):c.4-2A>G	LZTFL1	Likely pathogenic	criteria provided, single submitter
828163	NM_001276379.2(LZTFL1):c.3G>A (p.Met1Ile)	LZTFL1	Likely pathogenic	criteria provided, single submitter
2584608	NM_031200.3(CCR9):c.40G>T (p.Ala14Ser)	CCR9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1584603	NM_020347.4(LZTFL1):c.645C>T (p.Val215=)	LZTFL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3589182	NM_020347.4(LZTFL1):c.601-20C>T	LZTFL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1014254	NM_020347.4(LZTFL1):c.361G>A (p.Glu121Lys)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1018200	NM_020347.4(LZTFL1):c.625A>T (p.Ser209Cys)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1019150	NM_020347.4(LZTFL1):c.56G>A (p.Arg19His)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1026239	NM_020347.4(LZTFL1):c.812A>G (p.Tyr271Cys)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1058140	NM_020347.4(LZTFL1):c.401C>T (p.Thr134Ile)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1058235	NM_020347.4(LZTFL1):c.815G>A (p.Arg272Gln)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1314341	NM_020347.4(LZTFL1):c.324-3A>G	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1348088	NM_020347.4(LZTFL1):c.701A>G (p.Lys234Arg)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1356804	NM_020347.4(LZTFL1):c.766A>G (p.Met256Val)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1400857	NM_020347.4(LZTFL1):c.55C>A (p.Arg19Ser)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1426450	NM_020347.4(LZTFL1):c.281G>C (p.Trp94Ser)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1978297	NM_020347.4(LZTFL1):c.254G>T (p.Arg85Leu)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3061855	NM_020347.4(LZTFL1):c.778-3C>T	LZTFL1	Uncertain significance	criteria provided, single submitter
3352787	NM_020347.4(LZTFL1):c.323+6A>C	LZTFL1	Uncertain significance	criteria provided, single submitter
3352941	NM_020347.4(LZTFL1):c.289A>G (p.Lys97Glu)	LZTFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3354337	NM_020347.4(LZTFL1):c.324A>G (p.Arg108=)	LZTFL1	Uncertain significance	criteria provided, single submitter
3589176	NM_020347.4(LZTFL1):c.745A>G (p.Arg249Gly)	LZTFL1	Uncertain significance	criteria provided, single submitter

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
LZTFL1	Strong	Autosomal recessive	Bardet-Biedl syndrome 17	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LZTFL1	Orphanet:110	Bardet-Biedl syndrome

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
LZTFL1	HGNC:6741	ENSG00000163818	Q9NQ48	Leucine zipper transcription factor-like protein 1	gencc,clinvar
CCR9	HGNC:1610	ENSG00000173585	P51686	C-C chemokine receptor type 9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LZTFL1	Leucine zipper transcription factor-like protein 1	Regulates ciliary localization of the BBSome complex.
CCR9	C-C chemokine receptor type 9	Receptor for chemokine SCYA25/TECK.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LZTFL1	Other/Unknown	no		LZTFL1
CCR9	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR9

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
sperm	1
duodenum	1
small intestine Peyer’s patch	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LZTFL1	282	ubiquitous	marker	bronchial epithelial cell, sperm, epithelium of bronchus
CCR9	106	tissue_specific	yes	thymus, duodenum, small intestine Peyer’s patch

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCR9	1,479
LZTFL1	1,428

Intra-cohort edges

A	B	Sources
CCR9	LZTFL1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCR9	P51686	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LZTFL1	Q9NQ48	83.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
BBSome-mediated cargo-targeting to cilium	1	248.3×	0.043	LZTFL1
Cargo trafficking to the periciliary membrane	1	124.1×	0.043	LZTFL1
Chemokine receptors bind chemokines	1	93.6×	0.043	CCR9
Cilium Assembly	1	54.4×	0.046	LZTFL1
Class A/1 (Rhodopsin-like receptors)	1	37.1×	0.046	CCR9
Peptide ligand-binding receptors	1	37.1×	0.046	CCR9
Organelle biogenesis and maintenance	1	33.0×	0.046	LZTFL1
GPCR ligand binding	1	32.1×	0.046	CCR9
GPCR downstream signalling	1	21.7×	0.055	CCR9
Signaling by GPCR	1	20.0×	0.055	CCR9
G alpha (i) signalling events	1	19.5×	0.055	CCR9
Signal Transduction	1	5.1×	0.187	CCR9

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
negative regulation of protein localization to ciliary membrane	1	8426.0×	0.001	LZTFL1
CD8-positive, gamma-delta intraepithelial T cell differentiation	1	2808.7×	0.001	CCR9
negative regulation of protein localization to cilium	1	2808.7×	0.001	LZTFL1
cellular defense response	1	159.0×	0.019	CCR9
cell chemotaxis	1	92.6×	0.022	CCR9
calcium-mediated signaling	1	91.6×	0.022	CCR9
chemotaxis	1	68.0×	0.023	CCR9
positive regulation of cytosolic calcium ion concentration	1	58.5×	0.023	CCR9
flagellated sperm motility	1	58.5×	0.023	LZTFL1
immune response	1	23.5×	0.050	CCR9
G protein-coupled receptor signaling pathway	1	18.1×	0.056	CCR9
spermatogenesis	1	17.6×	0.056	LZTFL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCR9	1	3
LZTFL1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VERCIRNON	3	CCR9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CCR9	30	Binding:17, Functional:13

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
VERCIRNON	3	CCR9

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	1	CCR9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LZTFL1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LZTFL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.