LZTFL1

Summary

LZTFL1 (leucine zipper transcription factor like 1, HGNC:6741) is a protein-coding gene on chromosome 3p21.31, encoding Leucine zipper transcription factor-like protein 1 (Q9NQ48). Regulates ciliary localization of the BBSome complex.

This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells.

Source: NCBI Gene 54585 — RefSeq curated summary.

At a glance

• Gene–disease (curated): LZTFL1-related ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 234 total — 12 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 119
• MANE Select transcript: NM_020347

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6741
Approved symbol	LZTFL1
Name	leucine zipper transcription factor like 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	BBS17
Ensembl gene	ENSG00000163818
Ensembl biotype	protein_coding
OMIM	606568
Entrez	54585

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000296135, ENST00000411866, ENST00000418700, ENST00000440576, ENST00000445698, ENST00000469874, ENST00000472635, ENST00000478551, ENST00000480156, ENST00000483279, ENST00000490463, ENST00000492333, ENST00000495864, ENST00000539217, ENST00000684620, ENST00000699186, ENST00000699187, ENST00000699188, ENST00000862871, ENST00000862872

RefSeq mRNA: 14 — MANE Select: NM_020347 NM_001276378, NM_001276379, NM_001386451, NM_001386452, NM_001405920, NM_001405921, NM_001405922, NM_001405923, NM_001405924, NM_001405925, NM_001405926, NM_001405927, NM_001405928, NM_020347

CCDS: CCDS2731, CCDS63608, CCDS63609

Canonical transcript exons

ENST00000296135 — 10 exons

Exon	Start	End
ENSE00001367650	45823316	45826332
ENSE00001875678	45841989	45842119
ENSE00003474802	45833050	45833121
ENSE00003498347	45837927	45838051
ENSE00003602970	45830913	45830990
ENSE00003640833	45828439	45828615
ENSE00003641775	45831073	45831138
ENSE00003671912	45834238	45834298
ENSE00003680782	45827356	45827459
ENSE00003790767	45835590	45835784

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0132 / max 296.9723, expressed in 1760 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41905	16.3737	1727
41913	0.6132	84
41912	0.0213	6
41914	0.0050	3

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	97.63	gold quality
sperm	CL:0000019	97.44	gold quality
epithelium of bronchus	UBERON:0002031	97.38	gold quality
bronchus	UBERON:0002185	96.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.93	gold quality
caput epididymis	UBERON:0004358	95.28	gold quality
endothelial cell	CL:0000115	95.07	gold quality
choroid plexus epithelium	UBERON:0003911	95.01	gold quality
middle temporal gyrus	UBERON:0002771	94.57	gold quality
male germ cell	CL:0000015	94.06	gold quality
left testis	UBERON:0004533	93.75	gold quality
right testis	UBERON:0004534	93.40	gold quality
tendon of biceps brachii	UBERON:0008188	93.17	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.92	gold quality
testis	UBERON:0000473	92.89	gold quality
calcaneal tendon	UBERON:0003701	92.82	gold quality
corpus epididymis	UBERON:0004359	92.77	gold quality
tendon	UBERON:0000043	91.88	gold quality
metanephric glomerulus	UBERON:0004736	91.76	gold quality
renal glomerulus	UBERON:0000074	91.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.35	gold quality
nephron tubule	UBERON:0001231	91.03	gold quality
right uterine tube	UBERON:0001302	90.90	gold quality
germinal epithelium of ovary	UBERON:0001304	90.60	gold quality
primary visual cortex	UBERON:0002436	89.91	gold quality
superior frontal gyrus	UBERON:0002661	89.86	gold quality
tibia	UBERON:0000979	89.75	gold quality
epithelium of nasopharynx	UBERON:0001951	89.60	gold quality
nasopharynx	UBERON:0001728	89.58	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.01	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting LZTFL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3686	99.90	70.53	2432

Literature-anchored findings (GeneRIF, showing 15)

• LZTFL1 may inhibit tumorigenesis by stabilizing E-cadherin-mediated adherens junction formation and promoting epithelial cell differentiation. (PMID:20233871)
• Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling (PMID:22072986)
• The absence of LZTFL1 leads to a BBS phenotype with enhanced developmental abnormalities associated with cellular Shh dysfunction. LZTFL1 is a novel BBS gene (BBS17). (PMID:22510444)
• This special subtype of polydactyly in BBS patients is easily identified on clinical examination and prompts for priority sequencing of LZTFL1 (BBS17). (PMID:23692385)
• LZTFL1 binds beta-catenin in the cytoplasm of the cell and inhibited its nuclear translocation (PMID:25005785)
• LZTFL1 inhibits lung tumorigenesis (PMID:26364604)
• these data indicate that LZTFL1 modulates T cell activation and IL-5 levels. (PMID:26700766)
• LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of epithelial-mesenchymal transition markers in breast cancer cells. (PMID:31351450)
• Limited time window for retinal gene therapy in a preclinical model of ciliopathy. (PMID:32568387)
• lncRNA SNHG6 promotes hepatocellular carcinoma progression by interacting with HNRNPL/PTBP1 to facilitate SETD7/LZTFL1 mRNA destabilization. (PMID:34252487)
• Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus. (PMID:34737427)
• CRISPRi links COVID-19 GWAS loci to LZTFL1 and RAVER1. (PMID:34998241)
• Host genetic loci LZTFL1 and CCL2 associated with SARS-CoV-2 infection and severity of COVID-19. (PMID:35753602)
• LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway. (PMID:36966254)
• Association of 3p21.31 Locus (CXCR6 and LZTFL1) with COVID-19 Outcomes in Brazilian Hospitalyzed Subjects. (PMID:37578643)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lztfl1	ENSDARG00000105010
mus_musculus	Lztfl1	ENSMUSG00000025245
rattus_norvegicus	Lztfl1	ENSRNOG00000006244

Protein

Protein identifiers

Leucine zipper transcription factor-like protein 1 — Q9NQ48 (reviewed: Q9NQ48)

All UniProt accessions (8): A0A7P0TA24, A0A7P0TAT3, A0A7P0TBA5, A0A8V8TP88, C9J0R9, Q9NQ48, F8VR53, H7C488

UniProt curated annotations — full annotation on UniProt →

Function. Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function.

Subunit / interactions. Self-associates. Interacts with BBS9; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in prostate, ovary, stomach, pancreas, esophagus, breast, liver, bladder, kidney, thyroid, colon and lung (at protein level). Down-regulated in multiple primary tumors (at protein level). Detected in testis, heart, skeletal muscle, thymus, spleen, small intestine, and peripheral blood leukocytes.

Disease relevance. Bardet-Biedl syndrome 17 (BBS17) [MIM:615994] A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. The disease is caused by variants affecting the gene represented in this entry. Patients carrying LZTFL1 mutations manifest mesoaxial polydactyly, a clinical feature very uncommon for Bardet-Biedl syndrome. Some patients manifest situs inversus.

Similarity. Belongs to the LZTFL1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQ48-1	1	yes
Q9NQ48-2	2
Q9NQ48-3	3

RefSeq proteins (14): NP_001263307, NP_001263308, NP_001373380, NP_001373381, NP_001392849, NP_001392850, NP_001392851, NP_001392852, NP_001392853, NP_001392854, NP_001392855, NP_001392856, NP_001392857, NP_065080* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026157	LZTFL1	Family

Pfam: PF15294

UniProt features (13 total): sequence variant 4, splice variant 3, sequence conflict 2, chain 1, region of interest 1, mutagenesis site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ48-F1	83.74	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
24–25	increases bbs4, bbs8 and bbs9 ciliary localization.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5620922	BBSome-mediated cargo-targeting to cilium
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane

MSigDB gene sets: 491 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, KANG_FLUOROURACIL_RESISTANCE_UP, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, FOXO4_01, GOBP_MALE_GAMETE_GENERATION, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, KIM_GERMINAL_CENTER_T_HELPER_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (4): spermatogenesis (GO:0007283), flagellated sperm motility (GO:0030317), negative regulation of protein localization to cilium (GO:1903565), negative regulation of protein localization to ciliary membrane (GO:1903568)

GO Molecular Function (3): identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (5): manchette (GO:0002177), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), ciliary transition zone (GO:0035869)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
developmental process involved in reproduction	1
male gamete generation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
protein localization to cilium	1
regulation of protein localization to cilium	1
negative regulation of protein localization	1
protein localization to ciliary membrane	1
negative regulation of protein localization to cilium	1
regulation of protein localization to ciliary membrane	1
negative regulation of protein localization to cell periphery	1
negative regulation of protein localization to membrane	1
protein binding	1
microtubule cytoskeleton	1
intracellular anatomical structure	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

1259 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LZTFL1	SLC6A20	Q9NP91	840
LZTFL1	BBS9	P78514	833
LZTFL1	BBS7	Q8IWZ6	812
LZTFL1	FYCO1	Q9BQS8	805
LZTFL1	BBS2	Q9BXC9	798
LZTFL1	IFT27	Q9BW83	749
LZTFL1	BBS1	Q8NFJ9	745
LZTFL1	BBS12	Q6ZW61	732
LZTFL1	BBS4	Q96RK4	728
LZTFL1	BBS10	Q8TAM1	722
LZTFL1	BBS5	Q8N3I7	687
LZTFL1	CCR9	P51686	680
LZTFL1	CXCR6	O00574	670
LZTFL1	XCR1	P46094	662
LZTFL1	TTC8	Q8TAM2	630

IntAct

85 interactions, top by confidence:

A	B	Type	Score
LZTFL1	LZTFL1	psi-mi:“MI:0915”(physical association)	0.850
LZTFL1	BBS9	psi-mi:“MI:0914”(association)	0.850
LZTFL1	BBS9	psi-mi:“MI:0915”(physical association)	0.850
LZTFL1	BBS9	psi-mi:“MI:2364”(proximity)	0.850
BBS9	LZTFL1	psi-mi:“MI:0403”(colocalization)	0.850
BBS9	LZTFL1	psi-mi:“MI:0915”(physical association)	0.850
SDCBP	LZTFL1	psi-mi:“MI:0915”(physical association)	0.720
LZTFL1	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
NTAQ1	LZTFL1	psi-mi:“MI:0915”(physical association)	0.670
LZTFL1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.670
TRIM68	LZTFL1	psi-mi:“MI:0915”(physical association)	0.560
PSMA1	LZTFL1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (84): LZTFL1 (Two-hybrid), LZTFL1 (Two-hybrid), WDYHV1 (Two-hybrid), BBS2 (Affinity Capture-MS), BBS4 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), BBS7 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS9 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), LZTFL1 (Co-fractionation), SH3PXD2B (Co-fractionation), BBS5 (Affinity Capture-MS), BBS9 (Affinity Capture-MS)

ESM2 similar proteins: A5DPN3, A6ZML8, G2K449, O06636, O06637, O14043, O14468, O29209, O42062, P03421, P06101, P07533, P0CA98, P0CAA0, P0DJO8, P12579, P14503, P15630, P24567, P27383, P38413, P47453, P75353, P75481, Q28D79, Q37887, Q3ZBL4, Q4R6V9, Q4UJT1, Q54ID4, Q562C6, Q573D9, Q57780, Q58304, Q5PQN7, Q5RBR4, Q5ZKW2, Q6DHH7, Q6FS52, Q722M0

Diamond homologs: Q3ZBL4, Q4R6V9, Q562C6, Q5RBR4, Q9JHQ5, Q9NQ48

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
BBSome-mediated cargo-targeting to cilium	6	102.7×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
fat cell differentiation	5	25.9×	5e-04
cilium assembly	6	12.6×	8e-04
visual perception	5	11.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

234 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	9
Uncertain significance	104
Likely benign	94
Benign	1

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
126380	NM_020347.4(LZTFL1):c.260T>C (p.Leu87Pro)	Pathogenic
126381	NM_020347.4(LZTFL1):c.778G>T (p.Glu260Ter)	Pathogenic
1960140	NM_020347.4(LZTFL1):c.256C>T (p.Gln86Ter)	Pathogenic
196497	NM_020347.4(LZTFL1):c.322C>T (p.Arg108Ter)	Pathogenic
2038470	NM_020347.4(LZTFL1):c.561_563delinsTT (p.Lys187fs)	Pathogenic
2048577	NM_020347.4(LZTFL1):c.606dup (p.Ile203fs)	Pathogenic
2426538	NC_000003.11:g.(?45867806)(45877296_?)del	Pathogenic
2498317	NM_020347.4(LZTFL1):c.415dup (p.Ala139fs)	Pathogenic
2709040	NM_020347.4(LZTFL1):c.109C>T (p.Gln37Ter)	Pathogenic
3234009	NM_020347.4(LZTFL1):c.505A>T (p.Lys169Ter)	Pathogenic
3355445	NM_020347.4(LZTFL1):c.264del (p.Phe88fs)	Pathogenic
39770	NM_020347.4(LZTFL1):c.402_406del (p.Pro136fs)	Pathogenic
1333226	NM_020347.4(LZTFL1):c.457-1G>T	Likely pathogenic
1345900	NM_020347.4(LZTFL1):c.778-1G>A	Likely pathogenic
2780021	NM_020347.4(LZTFL1):c.384G>A (p.Lys128=)	Likely pathogenic
3589175	NM_020347.4(LZTFL1):c.745_746del (p.Arg249fs)	Likely pathogenic
3589184	NM_020347.4(LZTFL1):c.523-1G>A	Likely pathogenic
3589189	NM_020347.4(LZTFL1):c.4-2A>G	Likely pathogenic
504369	NM_020347.4(LZTFL1):c.214G>T (p.Glu72Ter)	Likely pathogenic
828163	NM_001276379.2(LZTFL1):c.3G>A (p.Met1Ile)	Likely pathogenic
950068	NM_020347.4(LZTFL1):c.385-2del	Likely pathogenic

SpliceAI

1939 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45826328:CATAT:C	acceptor_gain	1.0000
3:45826330:TAT:T	acceptor_gain	1.0000
3:45826331:ATC:A	acceptor_loss	1.0000
3:45826332:TC:T	acceptor_loss	1.0000
3:45826333:C:CA	acceptor_loss	1.0000
3:45826333:C:CC	acceptor_gain	1.0000
3:45826339:A:AC	acceptor_gain	1.0000
3:45827354:A:AC	donor_gain	1.0000
3:45827355:C:CC	donor_gain	1.0000
3:45828433:TCTGA:T	donor_loss	1.0000
3:45828434:CTGAC:C	donor_loss	1.0000
3:45828435:TGAC:T	donor_loss	1.0000
3:45828436:GAC:G	donor_loss	1.0000
3:45828438:CCTT:C	donor_loss	1.0000
3:45828615:CCTA:C	acceptor_gain	1.0000
3:45828616:C:CC	acceptor_gain	1.0000
3:45828617:T:C	acceptor_loss	1.0000
3:45830907:TTTCA:T	donor_loss	1.0000
3:45830908:TTCA:T	donor_loss	1.0000
3:45830909:TCA:T	donor_loss	1.0000
3:45830910:CA:C	donor_loss	1.0000
3:45830911:A:AG	donor_loss	1.0000
3:45830912:C:CA	donor_loss	1.0000
3:45831138:CCTT:C	acceptor_gain	1.0000
3:45831141:T:C	acceptor_gain	1.0000
3:45831141:T:TC	acceptor_gain	1.0000
3:45833044:TATTA:T	donor_loss	1.0000
3:45833046:TTAC:T	donor_loss	1.0000
3:45833047:TA:T	donor_loss	1.0000
3:45833048:ACC:A	donor_loss	1.0000

AlphaMissense

1969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45835642:C:G	A91P	0.998
3:45827370:C:A	R289S	0.997
3:45827370:C:G	R289S	0.997
3:45827404:A:G	L278P	0.997
3:45827426:A:C	Y271D	0.997
3:45827374:A:G	L288P	0.996
3:45827428:G:T	A270D	0.996
3:45835641:G:T	A91D	0.996
3:45835695:A:G	L73P	0.996
3:45835719:A:T	V65D	0.996
3:45837995:A:C	F20L	0.996
3:45837995:A:T	F20L	0.996
3:45837997:A:G	F20L	0.996
3:45835626:A:G	L96P	0.995
3:45827371:C:G	R289T	0.994
3:45827394:C:A	K281N	0.994
3:45827394:C:G	K281N	0.994
3:45828455:A:G	L254P	0.994
3:45828476:A:G	L247P	0.994
3:45835599:A:G	L105P	0.994
3:45835662:A:G	L84P	0.994
3:45837994:C:G	A21P	0.994
3:45831125:A:G	L157P	0.993
3:45827362:A:G	L292P	0.992
3:45827396:T:C	K281E	0.992
3:45827434:G:A	T268I	0.992
3:45827443:A:G	F265S	0.992
3:45828447:C:G	A257P	0.992
3:45835620:A:G	L98P	0.992
3:45835653:A:G	L87P	0.992

dbSNP variants (sampled 300 via entrez): RS1000001111 (3:45836534 A>C,G), RS1000066873 (3:45861637 TG>T), RS1000073794 (3:45872159 A>G), RS1000099454 (3:45870056 T>C,G), RS1000146887 (3:45913514 T>C), RS1000247122 (3:45889107 A>G), RS1000298349 (3:45902442 C>T), RS1000311685 (3:45843154 G>T), RS1000400834 (3:45850532 A>C), RS1000402559 (3:45910354 A>G), RS1000410940 (3:45850269 G>C), RS1000482923 (3:45882526 A>G), RS1000501224 (3:45865269 T>C), RS1000514644 (3:45867288 G>A,C), RS1000587285 (3:45873811 C>T)

Disease associations

OMIM: gene MIM:606568 | disease phenotypes: MIM:615994, MIM:209900

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 17	Strong	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
LZTFL1-related ciliopathy	Definitive	AR

Mondo (4): Bardet-Biedl syndrome 17 (MONDO:0014445), Bardet-Biedl syndrome 1 (MONDO:0008854), Bardet-Biedl syndrome (MONDO:0015229), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Bardet-Biedl syndrome (Orphanet:110), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

119 total (30 of 119 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000103	Polyuria
HP:0000107	Renal cyst
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000458	Anosmia
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_7	Acne (severe)	3.000000e-06
GCST004136_8	Methadone dose in opioid dependence	3.000000e-06
GCST009597_243	Multiple sclerosis	4.000000e-07
GCST90000255_22	Severe COVID-19 infection with respiratory failure (analysis I)	1.000000e-10
GCST90000256_1	Severe COVID-19 infection with respiratory failure (analysis II)	9.000000e-12
GCST90002382_563	Eosinophil percentage of white cells	4.000000e-09
GCST90013414_1	COVID-19 (critical illness vs population)	2.000000e-28

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007907	methadone dose measurement
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D058499	Retinal Dystrophies	C11.768.585.658
C537909	Bardet-Biedl syndrome 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
Air Pollutants	affects methylation, increases abundance, affects expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
Estradiol	affects expression, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
geraniol	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
corosolic acid	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	decreases expression, affects reaction	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases response to substance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

57 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00078091	Not specified	TERMINATED	Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
NCT00213811	Not specified	COMPLETED	Bardet-Biedl Syndrome Study: Clinical and Genetic Epidemiology Study in Adults
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT02329210	Not specified	RECRUITING	Clinical Registry Investigating Bardet-Biedl Syndrome
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04461444	Not specified	RECRUITING	COhort for Bardet-Bield Syndrome and Alström Syndrome for Translational Research Monocentric Interventional Study
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05183802	Not specified	APPROVED_FOR_MARKETING	An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS)
NCT05400278	Not specified	COMPLETED	Characterizing the Genotype and Phenotype in Adults With Bardet-Biedl Syndrome
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06615011	Not specified	NOT_YET_RECRUITING	Bardet Beidle Syndrome in a Syrian Adolescent : a Rare Case Report
NCT07602803	Not specified	COMPLETED	The Effect of GLP1 Agonists on Weight Loss in BBS Cohort in the UK
NCT07269665	EARLY_PHASE1	NOT_YET_RECRUITING	First-in-Human, Dose Escalation Trial of AXV-101 in BBS1-Related Retinal Degeneration
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging