IFT57

Summary

IFT57 (intraflagellar transport 57, HGNC:17367) is a protein-coding gene on chromosome 3q13.12-q13.13, encoding Intraflagellar transport protein 57 homolog (Q9NWB7). Required for the formation of cilia.

Predicted to enable DNA binding activity. Acts upstream of or within apoptotic process and regulation of apoptotic process. Located in ciliary base and photoreceptor connecting cilium. Part of intraciliary transport particle B. Implicated in orofaciodigital syndrome XVIII.

Source: NCBI Gene 55081 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Moderate, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 272 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 22
• MANE Select transcript: NM_018010

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17367
Approved symbol	IFT57
Name	intraflagellar transport 57
Location	3q13.12-q13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10147, HIPPI, MHS4R2
Ensembl gene	ENSG00000114446
Ensembl biotype	protein_coding
OMIM	606621
Entrez	55081

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264538, ENST00000465024, ENST00000468021, ENST00000478157, ENST00000485979, ENST00000492106, ENST00000878338, ENST00000939114, ENST00000939115, ENST00000939116, ENST00000939117, ENST00000939118, ENST00000939119, ENST00000947214

RefSeq mRNA: 1 — MANE Select: NM_018010 NM_018010

CCDS: CCDS2951

Canonical transcript exons

ENST00000264538 — 11 exons

Exon	Start	End
ENSE00000967369	108165431	108165493
ENSE00000967370	108163663	108163729
ENSE00000967371	108160812	108162655
ENSE00001009792	108222111	108222424
ENSE00003484415	108167793	108167864
ENSE00003494805	108166854	108166985
ENSE00003503574	108218535	108218653
ENSE00003505630	108219410	108219572
ENSE00003510708	108213931	108214021
ENSE00003552380	108191521	108191643
ENSE00003633482	108206628	108206696

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.2218 / max 412.5167, expressed in 1804 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43667	37.8143	1801
43666	1.4506	643
202873	0.3324	149
43665	0.2044	29
43662	0.1998	35
43664	0.1351	30
43663	0.0852	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.31	gold quality
epithelium of bronchus	UBERON:0002031	99.05	gold quality
bronchus	UBERON:0002185	98.83	gold quality
sperm	CL:0000019	98.61	gold quality
male germ cell	CL:0000015	97.84	gold quality
caput epididymis	UBERON:0004358	97.84	gold quality
left testis	UBERON:0004533	97.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.54	gold quality
right testis	UBERON:0004534	97.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.15	gold quality
epithelium of nasopharynx	UBERON:0001951	96.95	gold quality
nasopharynx	UBERON:0001728	96.93	gold quality
corpus epididymis	UBERON:0004359	96.89	gold quality
testis	UBERON:0000473	96.50	gold quality
right uterine tube	UBERON:0001302	96.36	gold quality
calcaneal tendon	UBERON:0003701	95.93	gold quality
visceral pleura	UBERON:0002401	95.32	gold quality
choroid plexus epithelium	UBERON:0003911	95.28	gold quality
pigmented layer of retina	UBERON:0001782	95.12	gold quality
germinal epithelium of ovary	UBERON:0001304	95.10	gold quality
lung	UBERON:0002048	95.07	gold quality
nephron tubule	UBERON:0001231	95.06	gold quality
cervix squamous epithelium	UBERON:0006922	94.98	gold quality
lower lobe of lung	UBERON:0008949	94.95	gold quality
renal glomerulus	UBERON:0000074	94.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.79	gold quality
metanephric glomerulus	UBERON:0004736	94.63	gold quality
upper lobe of lung	UBERON:0008948	94.61	gold quality
upper lobe of left lung	UBERON:0008952	94.57	gold quality
cauda epididymis	UBERON:0004360	94.49	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	61.98
E-HCAD-5	yes	32.39
E-GEOD-134144	yes	30.19
E-HCAD-1	yes	29.42
E-MTAB-10287	yes	25.46
E-GEOD-130148	yes	13.87
E-MTAB-9388	yes	6.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting IFT57, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-944	99.82	70.85	3042

Literature-anchored findings (GeneRIF, showing 11)

• Results show that pro-apoptotic Hippi-Hip-1 heterodimers can recruit procaspase-8 into a complex of Hippi, Hip-1 and procaspase-8, and launch apoptosis through components of the ’extrinsic’ cell-death pathway. (PMID:11788820)
• critical for the death-promoting effects of mutant huntingtin protein in cultured cells (PMID:11807533)
• Hippi interacts with the viral death protein Apoptin. (PMID:12745083)
• Hippi expression induced apoptosis by releasing AIF and cytochrome c from mitochondria, activation of caspase-1 and caspase-3, and altering the expression of apoptotic genes and genes involved in mitochondrial complex I and II. (PMID:16364650)
• Crystals of the pDED of HIPPI were grown in space group P4(1), with unit-cell parameters a = b = 77.42, c = 33.31 A and a calculated Matthews coefficient of 1.88 A3 Da(-1) (33% solvent content) with two molecules per asymmetric unit. (PMID:17142908)
• In summary, we showed that HIPPI could interact with the putative promoter sequence of caspase-1 and increased the expression of the downstream gene suggesting that HIPPI could act as transcription regulator. (PMID:17173859)
• Over-expression of BLOC1S2 in presence or absence of HIPPI does not induce apoptosis. However, BLOC1S2 & HIPPI sensitize NCH89 glioblastoma cells to pro-apoptotic actions of staurosporine & death ligand TRAIL. (PMID:18188704)
• novel transcription regulatory mechanism of REST by HIPPI may contribute to the deregulation of transcription observed in the cell model of Huntington disease. (PMID:21832040)
• HIPPI-P53 interaction was necessary for HIPPI mediated up-regulation of Caspase1 gene. (PMID:21943362)
• sequencing of IFT57 in 13 OFDS subjects and 12 subjects with Ellis-Van Creveld syndrome was negative. This report identifies the implication of IFT57 in human pathology and highlights the first description of a ciliary transport defect in OFDS, extending the genetic heterogeneity of this subgroup of ciliopathies. (PMID:27060890)
• CD47 and IFT57 Are Colinear Genes That Are Highly Coexpressed in Most Cancers and Exhibit Parallel Cancer-Specific Correlations with Survival. (PMID:39201643)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ift57	ENSDARG00000021022
mus_musculus	Ift57	ENSMUSG00000032965
rattus_norvegicus	Ift57	ENSRNOG00000001958
drosophila_melanogaster	IFT57	FBGN0031550
caenorhabditis_elegans	che-13	WBGENE00000492

Protein

Protein identifiers

Intraflagellar transport protein 57 homolog — Q9NWB7 (reviewed: Q9NWB7)

Alternative names: Dermal papilla-derived protein 8, Estrogen-related receptor beta-like protein 1, HIP1-interacting protein, MHS4R2

All UniProt accessions (4): B4DQL5, C9JB84, Q9NWB7, F8WBM2

UniProt curated annotations — full annotation on UniProt →

Function. Required for the formation of cilia. Plays an indirect role in sonic hedgehog signaling, cilia being required for all activity of the hedgehog pathway. Together with RAB23 and KIF17, it is required for the localization of specific G protein-coupled receptors, such as dopamime receptor DRD1, to primary cilia. Has pro-apoptotic function via its interaction with HIP1, leading to recruit caspase-8 (CASP8) and trigger apoptosis. Has the ability to bind DNA sequence motif 5’-AAAGACATG-3’ present in the promoter of caspase genes such as CASP1, CASP8 and CASP10, suggesting that it may act as a transcription regulator; however the relevance of such function remains unclear.

Subunit / interactions. Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88. Interacts with IFT20. Interacts with IFT88. Interacts with IFT80, IFT-81, IFT74, IFT172, IFT70B and KIF17. Interacts with BLOC1S2. Interacts with RYBP. Interacts with HOMER1; the interaction possibly prevents the pro-apoptotic effects of IFT57. Interacts with HIP1. In normal conditions, it poorly interacts with HIP1, HIP1 being strongly associated with HTT. However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57, leading to apoptosis. Interacts with BFAR. Interacts with TTC25. Interacts with USH1G. Interacts with chicken anemia virus protein apoptin.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium basal body.

Tissue specificity. Present in many tissues such as brain, thymus, lymph node, lung, liver, skin and kidney (at protein level).

Disease relevance. Orofaciodigital syndrome 18 (OFD18) [MIM:617927] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD18 is an autosomal recessive form characterized by short stature, brachymesophalangy, pre- and postaxial polysyndactyly, and stocky femoral necks, as well as oral anomalies and dysmorphic facial features. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The pseudo DED region (pDED) mediates the interaction with HIP1.

Similarity. Belongs to the IFT57 family.

RefSeq proteins (1): NP_060480* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019530	Intra-flagellar_transport_57	Family

Pfam: PF10498

UniProt features (5 total): chain 1, region of interest 1, coiled-coil region 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWB7-F1	76.92	0.36

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
409	impairs the interaction with hip1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 343 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOCC_MICROTUBULE_ORGANIZING_CENTER, CREB_Q4, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, FOSTER_TOLERANT_MACROPHAGE_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS

GO Biological Process (13): neural tube closure (GO:0001843), heart looping (GO:0001947), apoptotic process (GO:0006915), smoothened signaling pathway (GO:0007224), negative regulation of keratinocyte proliferation (GO:0010839), intraciliary anterograde transport (GO:0035720), intraciliary transport (GO:0042073), regulation of apoptotic process (GO:0042981), keratinocyte proliferation (GO:0043616), motile cilium assembly (GO:0044458), cilium assembly (GO:0060271), non-motile cilium assembly (GO:1905515), left/right pattern formation (GO:0060972)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (15): Golgi apparatus (GO:0005794), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cilium (GO:0005929), axoneme (GO:0005930), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), photoreceptor connecting cilium (GO:0032391), ciliary basal body (GO:0036064), dendrite terminus (GO:0044292), ciliary tip (GO:0097542), ciliary base (GO:0097546), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Hedgehog	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	7
cilium	4
intraciliary transport particle	3
cilium organization	2
cilium assembly	2
microtubule organizing center	2
protein-containing complex	2
ciliary transition zone	2
primary neural tube formation	1
tube closure	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell surface receptor signaling pathway	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
negative regulation of epithelial cell proliferation	1
intraciliary transport	1
transport along microtubule	1
apoptotic process	1
regulation of programmed cell death	1
epithelial cell proliferation	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
regionalization	1
nucleic acid binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule cytoskeleton	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

1332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT57	IFT52	Q9Y366	997
IFT57	IFT88	Q13099	996
IFT57	IFT20	Q8IY31	996
IFT57	IFT54	Q8TDR0	995
IFT57	IFT38	Q96AJ1	995
IFT57	IFT80	Q9P2H3	995
IFT57	IFT172	Q9UG01	988
IFT57	IFT27	Q9BW83	986
IFT57	IFT46	Q9NQC8	982
IFT57	IFT25	Q9Y547	979
IFT57	IFT81	Q8WYA0	979
IFT57	IFT74	Q96LB3	972
IFT57	IFT22	Q9H7X7	959
IFT57	IFT70B	Q8N4P2	937
IFT57	IFT56	A0AVF1	884

IntAct

96 interactions, top by confidence:

A	B	Type	Score
IFT57	CORO1A	psi-mi:“MI:0914”(association)	0.790
IFT70A	IFT56	psi-mi:“MI:0914”(association)	0.790
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT22	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT172	IFT56	psi-mi:“MI:0914”(association)	0.590
EXOC5	IFT57	psi-mi:“MI:0915”(physical association)	0.560
SKA2	IFT57	psi-mi:“MI:0915”(physical association)	0.560
	IFT57	psi-mi:“MI:0915”(physical association)	0.560
YAF2	IFT57	psi-mi:“MI:0915”(physical association)	0.560
IFT20	IFT57	psi-mi:“MI:0915”(physical association)	0.560
HTT	IFT57	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (195): IFT57 (Two-hybrid), IFT57 (Affinity Capture-Western), IFT172 (Affinity Capture-MS), TTC26 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS), EHBP1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), CLUAP1 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), HOMER1 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER3 (Affinity Capture-MS), IFT88 (Affinity Capture-MS), STX18 (Affinity Capture-MS)

ESM2 similar proteins: A0A5G2QD80, A8E5U3, A9ULY7, O75934, Q13503, Q13561, Q16891, Q1HQF2, Q28DG8, Q28HX4, Q28Y46, Q2TBU8, Q3ZCF0, Q4R6N3, Q4V909, Q5EA95, Q5FW42, Q5PPY2, Q5R561, Q5RAX7, Q5RE46, Q5REX6, Q5RKQ0, Q5U1Z0, Q5ZKJ4, Q66J30, Q6AYH5, Q6DF11, Q6DFL5, Q6IRB3, Q6IVW0, Q6NY52, Q6PBE2, Q6TA25, Q7K2D2, Q7PZ25, Q7T3H1, Q7ZXA8, Q8BMG7, Q8BXG3

Diamond homologs: A9ULY7, Q28HX4, Q2XQY7, Q5EA95, Q6IVW0, Q8BXG3, Q93833, Q9NWB7, Q9VQS5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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
Intraflagellar transport	12	58.6×	1e-16

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	11	171.2×	4e-21
intraciliary transport	8	78.8×	9e-12
non-motile cilium assembly	7	35.7×	1e-07
cilium assembly	20	25.8×	4e-21
smoothened signaling pathway	7	22.2×	3e-06
kidney development	5	12.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	152
Likely benign	85
Benign	19

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
506288	NM_018010.4(IFT57):c.777G>A (p.Lys259=)	Pathogenic
592142	NM_018010.4(IFT57):c.585+3A>G	Likely pathogenic

SpliceAI

1279 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108162652:GGAG:G	acceptor_gain	1.0000
3:108162653:GAG:G	acceptor_gain	1.0000
3:108162656:C:CC	acceptor_gain	1.0000
3:108162657:T:A	acceptor_loss	1.0000
3:108163657:ACT:A	donor_loss	1.0000
3:108163658:CT:C	donor_loss	1.0000
3:108163659:TTACC:T	donor_loss	1.0000
3:108163661:ACC:A	donor_loss	1.0000
3:108163662:CCA:C	donor_gain	1.0000
3:108163728:ACC:A	acceptor_loss	1.0000
3:108163729:CC:C	acceptor_loss	1.0000
3:108163730:C:A	acceptor_loss	1.0000
3:108163731:T:A	acceptor_loss	1.0000
3:108163734:CA:C	acceptor_gain	1.0000
3:108163735:A:C	acceptor_gain	1.0000
3:108166862:G:C	donor_gain	1.0000
3:108188130:T:TA	donor_gain	1.0000
3:108191519:A:C	donor_loss	1.0000
3:108191639:ATATC:A	acceptor_gain	1.0000
3:108191640:TATC:T	acceptor_gain	1.0000
3:108191641:ATC:A	acceptor_gain	1.0000
3:108191641:ATCC:A	acceptor_loss	1.0000
3:108191642:TC:T	acceptor_gain	1.0000
3:108191643:CC:C	acceptor_gain	1.0000
3:108191643:CCTA:C	acceptor_loss	1.0000
3:108191644:C:CC	acceptor_gain	1.0000
3:108191645:T:C	acceptor_loss	1.0000
3:108206698:T:C	acceptor_gain	1.0000
3:108213927:ATAC:A	donor_loss	1.0000
3:108213928:TA:T	donor_loss	1.0000

AlphaMissense

2836 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:108167861:A:G	W261R	1.000
3:108167861:A:T	W261R	1.000
3:108166927:C:G	R303P	0.999
3:108167859:C:A	W261C	0.999
3:108167859:C:G	W261C	0.999
3:108191549:A:G	L250P	0.999
3:108191564:C:G	R245P	0.999
3:108191583:A:G	W239R	0.999
3:108191583:A:T	W239R	0.999
3:108191581:C:A	W239C	0.998
3:108191581:C:G	W239C	0.998
3:108218613:C:T	G139D	0.998
3:108218622:A:G	L136S	0.998
3:108222171:A:G	L51P	0.997
3:108191582:C:G	W239S	0.996
3:108167856:T:A	R262S	0.995
3:108167856:T:G	R262S	0.995
3:108167860:C:G	W261S	0.995
3:108191549:A:T	L250Q	0.995
3:108218574:G:T	A152D	0.995
3:108191558:A:G	L247P	0.994
3:108218589:A:T	V147D	0.994
3:108219564:A:G	F74S	0.994
3:108166903:A:G	L311P	0.993
3:108219508:A:G	W93R	0.993
3:108219508:A:T	W93R	0.993
3:108167857:C:G	R262T	0.992
3:108191576:A:G	L241P	0.992
3:108218575:C:G	A152P	0.992
3:108218586:A:G	L148P	0.992

dbSNP variants (sampled 300 via entrez): RS1000001123 (3:108214895 T>C), RS1000011441 (3:108171937 G>A), RS1000029312 (3:108201721 A>G), RS1000066187 (3:108192736 A>G,T), RS1000101273 (3:108215647 A>T), RS1000121323 (3:108177756 C>T), RS1000159594 (3:108214757 A>C), RS1000165633 (3:108206083 A>C,T), RS1000201000 (3:108165867 G>A), RS1000318983 (3:108169949 T>C), RS1000380290 (3:108191046 C>T), RS1000382043 (3:108162047 A>T), RS1000466694 (3:108205414 C>T), RS1000479254 (3:108218933 G>A), RS1000485040 (3:108184258 T>C)

Disease associations

OMIM: gene MIM:606621 | disease phenotypes: MIM:617927, MIM:209900

GenCC curated gene-disease

Disease	Classification	Inheritance
orofaciodigital syndrome 18	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Moderate	AR

Mondo (2): orofaciodigital syndrome 18 (MONDO:0054770), Bardet-Biedl syndrome (MONDO:0015229)

Orphanet (2): Orofaciodigital syndrome type 18 (Orphanet:508501), Bardet-Biedl syndrome (Orphanet:110)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000191	Accessory oral frenulum
HP:0000321	Square face
HP:0000322	Short philtrum
HP:0000350	Small forehead
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000582	Upslanted palpebral fissure
HP:0000699	Diastema
HP:0000891	Cervical ribs
HP:0000954	Single transverse palmar crease
HP:0001156	Brachydactyly
HP:0001852	Sandal gap
HP:0002750	Delayed skeletal maturation
HP:0002857	Genu valgum
HP:0004322	Short stature
HP:0005819	Short middle phalanx of finger
HP:0009882	Short distal phalanx of finger
HP:0100258	Preaxial polydactyly
HP:0100259	Postaxial polydactyly
HP:0410030	Cleft lip

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006922_10	Regular attendance at a religious group	8.000000e-12
GCST008103_22	Bipolar disorder	2.000000e-08
GCST010988_109	Adult body size	3.000000e-10
GCST90000047_55	Age at first sexual intercourse	3.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment, increases expression	6
Tobacco Smoke Pollution	affects expression, decreases expression	3
trichostatin A	affects expression, decreases expression	2
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
arsenite	affects expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
pentanal	decreases expression	1
arsenic disulfide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression, increases reaction	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Carbamazepine	affects expression	1

Clinical trials (associated diseases)

17 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
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
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