IFT46

Summary

IFT46 (intraflagellar transport 46, HGNC:26146) is a protein-coding gene on chromosome 11q23.3, encoding Intraflagellar transport protein 46 homolog (Q9NQC8). Forms part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia.

Predicted to be involved in cilium assembly; intraciliary transport; and protein stabilization. Predicted to act upstream of or within smoothened signaling pathway. Located in cytoplasm. Part of intraciliary transport particle B.

Source: NCBI Gene 56912 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001168618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26146
Approved symbol	IFT46
Name	intraflagellar transport 46
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	C11orf2, FLJ21827, FAP32, CFAP32
Ensembl gene	ENSG00000118096
Ensembl biotype	protein_coding
OMIM	620506
Entrez	56912

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264020, ENST00000264021, ENST00000525060, ENST00000527868, ENST00000528378, ENST00000530185, ENST00000530872, ENST00000531201, ENST00000531939, ENST00000533918, ENST00000534114, ENST00000534156, ENST00000672656

RefSeq mRNA: 2 — MANE Select: NM_001168618 NM_001168618, NM_020153

CCDS: CCDS53718, CCDS8399

Canonical transcript exons

ENST00000264021 — 12 exons

Exon	Start	End
ENSE00001053493	118564965	118565061
ENSE00001269870	118544543	118545011
ENSE00002150985	118565790	118565931
ENSE00003458344	118551786	118551852
ENSE00003477024	118554990	118555083
ENSE00003477432	118545409	118545494
ENSE00003494040	118552214	118552335
ENSE00003549761	118554459	118554587
ENSE00003578770	118545793	118545853
ENSE00003597191	118559785	118559864
ENSE00003609498	118555248	118555322
ENSE00003788341	118556906	118557045

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.9409 / max 310.2371, expressed in 1767 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122608	9.4049	1706
122609	6.5360	1629

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.51	gold quality
bronchial epithelial cell	CL:0002328	95.15	gold quality
epithelium of bronchus	UBERON:0002031	95.04	gold quality
bronchus	UBERON:0002185	94.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.61	gold quality
calcaneal tendon	UBERON:0003701	93.36	gold quality
adenohypophysis	UBERON:0002196	92.76	gold quality
islet of Langerhans	UBERON:0000006	92.73	gold quality
cerebellar hemisphere	UBERON:0002245	92.26	gold quality
cerebellar cortex	UBERON:0002129	92.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.09	gold quality
pituitary gland	UBERON:0000007	91.79	gold quality
cerebellum	UBERON:0002037	91.23	gold quality
nucleus accumbens	UBERON:0001882	90.95	gold quality
right frontal lobe	UBERON:0002810	90.94	gold quality
right testis	UBERON:0004534	90.87	gold quality
caput epididymis	UBERON:0004358	90.78	gold quality
left testis	UBERON:0004533	90.71	gold quality
caudate nucleus	UBERON:0001873	90.58	gold quality
anterior cingulate cortex	UBERON:0009835	90.58	gold quality
endocervix	UBERON:0000458	90.57	gold quality
cingulate cortex	UBERON:0003027	90.50	gold quality
ventricular zone	UBERON:0003053	90.47	gold quality
prefrontal cortex	UBERON:0000451	90.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.08	gold quality
hypothalamus	UBERON:0001898	90.06	gold quality
right adrenal gland	UBERON:0001233	89.93	gold quality
right lobe of thyroid gland	UBERON:0001119	89.92	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.07
E-ENAD-17	no	350.34
E-GEOD-75367	no	93.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting IFT46, 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-3163	100.00	77.23	8605
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-3680-5P	98.06	66.20	394
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-2276-5P	96.27	65.85	937

Literature-anchored findings (GeneRIF, showing 1)

• the ciliary protein IFT46 has a specific function in chondrocytes and is also essential for normal development of vertebrates. (PMID:17720815)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ift46	ENSDARG00000011240
mus_musculus	Ift46	ENSMUSG00000002031
rattus_norvegicus	Ift46	ENSRNOG00000013919
drosophila_melanogaster	IFT46	FBGN0032692
caenorhabditis_elegans		WBGENE00001122

Protein

Protein identifiers

Intraflagellar transport protein 46 homolog — Q9NQC8 (reviewed: Q9NQC8)

All UniProt accessions (8): Q9NQC8, A0A5F9ZH13, E9PIM8, E9PKW0, E9PMR8, E9PR06, E9PRT0, E9PSB9

UniProt curated annotations — full annotation on UniProt →

Function. Forms part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia. May play a role in chondrocyte maturation and skeletogenesis.

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 IFT57, IFT88 and DAW1. Interacts with IFT56. Interacts with ARL13B. Interacts with TTC25. Interacts with IFT70B.

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

Similarity. Belongs to the IFT46 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQC8-1	1	yes
Q9NQC8-2	2

RefSeq proteins (2): NP_001162089, NP_064538 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022088	Intraflagellar_transp_cmplxB	Family

Pfam: PF12317

UniProt features (12 total): sequence conflict 3, compositionally biased region 3, region of interest 2, chain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQC8-F1	70.24	0.07

Functional residue map

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

Post-translational modifications (1): 286

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 141 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, YANG_BREAST_CANCER_ESR1_LASER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, EFC_Q6, UEDA_PERIFERAL_CLOCK, MARTINEZ_RB1_TARGETS_DN, KOYAMA_SEMA3B_TARGETS_UP, GOBP_CILIUM_ORGANIZATION, GOBP_PROTEIN_STABILIZATION, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_STABILITY, DOUGLAS_BMI1_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (5): smoothened signaling pathway (GO:0007224), intraciliary anterograde transport (GO:0035720), intraciliary transport (GO:0042073), protein stabilization (GO:0050821), cilium assembly (GO:0060271)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (12): cytoplasm (GO:0005737), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cilium (GO:0005929), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), motile cilium (GO:0031514), ciliary tip (GO:0097542), cytoskeleton (GO:0005856), ciliary basal body (GO:0036064), cell projection (GO:0042995), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cilium	4
cellular anatomical structure	4
intraciliary transport particle	3
cilium organization	2
microtubule organizing center	2
protein-containing complex	2
cell surface receptor signaling pathway	1
intraciliary transport	1
transport along microtubule	1
regulation of protein stability	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
binding	1
intracellular anatomical structure	1
centriole	1
microtubule cytoskeleton	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular membraneless organelle	1
cell projection	1
plasma membrane region	1

Protein interactions and networks

STRING

2355 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT46	IFT70B	Q8N4P2	997
IFT46	IFT52	Q9Y366	997
IFT46	IFT81	Q8WYA0	996
IFT46	IFT88	Q13099	996
IFT46	IFT74	Q96LB3	996
IFT46	IFT27	Q9BW83	995
IFT46	IFT56	A0AVF1	993
IFT46	IFT25	Q9Y547	992
IFT46	IFT22	Q9H7X7	992
IFT46	DAW1	Q8N136	983
IFT46	IFT57	Q9NWB7	982
IFT46	IFT54	Q8TDR0	977
IFT46	IFT20	Q8IY31	965
IFT46	IFT80	Q9P2H3	963
IFT46	IFT172	Q9UG01	944

IntAct

71 interactions, top by confidence:

A	B	Type	Score
IFT56	IFT70A	psi-mi:“MI:0914”(association)	0.790
IFT70A	IFT56	psi-mi:“MI:0914”(association)	0.790
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT46	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT22	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT81	NDC80	psi-mi:“MI:0914”(association)	0.640
IFT172	IFT56	psi-mi:“MI:0914”(association)	0.590

BioGRID (75): IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Proximity Label-MS), UBXN10 (Reconstituted Complex), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), IFT46 (Affinity Capture-MS)

ESM2 similar proteins: A1A4M2, A3KN28, A4VCH4, A5D8P8, A5PJA8, A6QLP7, A7E2M3, A9JRA0, O13097, O43237, O70585, O88597, P16967, P43307, P53815, P83094, Q0IHY5, Q14165, Q14457, Q1LZB4, Q4A1L3, Q4A1L4, Q4A1L5, Q4KUS2, Q4R5P6, Q4R5V2, Q5JSJ4, Q5R4X4, Q5R878, Q5RE09, Q5UCC4, Q5XI83, Q5ZKS6, Q62698, Q62768, Q68FJ8, Q68FW3, Q6DFL2, Q6GP52, Q6PDL0

Diamond homologs: A2T2X4, A7MBP4, Q0G838, Q1LZB4, Q5DHJ5, Q6AXQ9, Q9DB07, Q9NQC8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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	14	100.2×	6e-24

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	13	295.6×	4e-29
intraciliary transport	10	144.0×	4e-18
negative regulation of keratinocyte proliferation	5	90.0×	1e-07
keratinocyte proliferation	5	74.5×	2e-07
non-motile cilium assembly	7	52.1×	3e-09
smoothened signaling pathway	9	41.8×	4e-11
cilium assembly	16	30.2×	3e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1579 predictions. Top by Δscore:

Variant	Effect	Δscore
11:118545007:AAATG:A	acceptor_gain	1.0000
11:118545008:AATG:A	acceptor_gain	1.0000
11:118545009:ATG:A	acceptor_gain	1.0000
11:118545010:TG:T	acceptor_gain	1.0000
11:118545011:GC:G	acceptor_loss	1.0000
11:118545012:C:CC	acceptor_gain	1.0000
11:118545012:C:T	acceptor_loss	1.0000
11:118545516:A:T	acceptor_gain	1.0000
11:118545786:AACTC:A	donor_loss	1.0000
11:118545787:ACT:A	donor_loss	1.0000
11:118545788:CTC:C	donor_loss	1.0000
11:118545789:TCA:T	donor_loss	1.0000
11:118545790:CA:C	donor_loss	1.0000
11:118545791:ACCAC:A	donor_loss	1.0000
11:118545792:C:CT	donor_loss	1.0000
11:118545792:CCA:C	donor_gain	1.0000
11:118545849:CTTAC:C	acceptor_gain	1.0000
11:118545854:C:CG	acceptor_loss	1.0000
11:118552331:TGTTG:T	acceptor_gain	1.0000
11:118552333:TTG:T	acceptor_gain	1.0000
11:118552334:TG:T	acceptor_gain	1.0000
11:118552336:C:CC	acceptor_gain	1.0000
11:118554457:A:AC	donor_gain	1.0000
11:118554458:C:CT	donor_gain	1.0000
11:118554458:CT:C	donor_gain	1.0000
11:118554985:TATA:T	donor_loss	1.0000
11:118554986:ATAC:A	donor_loss	1.0000
11:118554987:TACC:T	donor_loss	1.0000
11:118554988:ACCT:A	donor_loss	1.0000
11:118555082:ACC:A	acceptor_loss	1.0000

AlphaMissense

2037 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:118552275:A:G	W182R	0.999
11:118552275:A:T	W182R	0.999
11:118554496:A:G	L149P	0.999
11:118555012:C:A	G111V	0.999
11:118555012:C:T	G111E	0.999
11:118555013:C:A	G111W	0.999
11:118555013:C:G	G111R	0.999
11:118555013:C:T	G111R	0.999
11:118555015:A:T	V110D	0.999
11:118555018:G:T	A109D	0.999
11:118555019:C:G	A109P	0.999
11:118545434:A:G	L265P	0.998
11:118551818:A:G	W214R	0.998
11:118551818:A:T	W214R	0.998
11:118552273:C:A	W182C	0.998
11:118552273:C:G	W182C	0.998
11:118554553:C:T	G130D	0.998
11:118554554:C:G	G130R	0.998
11:118554586:A:T	V119D	0.997
11:118555038:G:C	F102L	0.997
11:118555038:G:T	F102L	0.997
11:118555040:A:G	F102L	0.997
11:118555266:A:G	L81P	0.997
11:118551829:A:G	L210P	0.996
11:118552274:C:G	W182S	0.996
11:118554490:A:G	L151S	0.996
11:118554502:A:G	L147P	0.996
11:118554553:C:A	G130V	0.996
11:118554990:C:A	K118N	0.996
11:118554990:C:G	K118N	0.996

dbSNP variants (sampled 300 via entrez): RS1000130676 (11:118553382 G>A), RS1000219480 (11:118550217 G>A), RS1000243255 (11:118556650 C>T), RS1000289841 (11:118550010 G>A), RS1000373287 (11:118564677 A>G), RS1000375857 (11:118570493 C>A,G), RS1000823802 (11:118562819 A>G), RS1000993213 (11:118575183 T>A), RS1001315245 (11:118565154 C>T), RS1001339403 (11:118571540 C>T), RS1001388557 (11:118564781 G>A), RS1001456622 (11:118569019 G>A), RS1001545999 (11:118550860 C>G), RS1001578541 (11:118544165 C>G), RS1001620372 (11:118556759 T>C)

Disease associations

OMIM: gene MIM:620506 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010204_64	Low density lipoprotein cholesterol levels	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, affects expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
corosolic acid	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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