IFT140

Summary

IFT140 (intraflagellar transport 140, HGNC:29077) is a protein-coding gene on chromosome 16p13.3, encoding Intraflagellar transport protein 140 homolog (Q96RY7). Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).

This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease.

Source: NCBI Gene 9742 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant polycystic kidney disease (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 2,258 total — 97 pathogenic, 101 likely-pathogenic
• Phenotypes (HPO): 245
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_014714

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29077
Approved symbol	IFT140
Name	intraflagellar transport 140
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	gs114, KIAA0590
Ensembl gene	ENSG00000187535
Ensembl biotype	protein_coding
OMIM	614620
Entrez	9742

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000361339, ENST00000397417, ENST00000426508, ENST00000439987, ENST00000561954, ENST00000565298, ENST00000566052, ENST00000566818, ENST00000568837, ENST00000569646, ENST00000569812, ENST00000889168, ENST00000889169, ENST00000889170, ENST00000914239, ENST00000962400, ENST00000962401, ENST00000962402

RefSeq mRNA: 1 — MANE Select: NM_014714 NM_014714

CCDS: CCDS10439

Canonical transcript exons

ENST00000426508 — 31 exons

Exon	Start	End
ENSE00001528613	1510427	1511150
ENSE00001739109	1611968	1612072
ENSE00001798630	1610664	1610853
ENSE00003465457	1592467	1592588
ENSE00003468624	1563997	1564162
ENSE00003479805	1557935	1558134
ENSE00003499823	1602370	1602591
ENSE00003505531	1589605	1589780
ENSE00003514742	1584217	1584420
ENSE00003519271	1561985	1562116
ENSE00003552357	1568217	1568334
ENSE00003563621	1518216	1518357
ENSE00003563738	1566161	1566291
ENSE00003566403	1571407	1571534
ENSE00003567173	1520602	1520808
ENSE00003577717	1525231	1525326
ENSE00003578613	1525887	1526077
ENSE00003582581	1607120	1607297
ENSE00003585732	1519881	1520047
ENSE00003586071	1524552	1524695
ENSE00003586558	1592176	1592318
ENSE00003590291	1524784	1524916
ENSE00003599003	1520131	1520343
ENSE00003602254	1523518	1523700
ENSE00003621672	1523828	1523956
ENSE00003626926	1587198	1587304
ENSE00003648176	1580759	1580850
ENSE00003649211	1586130	1586275
ENSE00003656632	1583314	1583386
ENSE00003656970	1587933	1588024
ENSE00003659131	1526619	1526796

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 95.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5788 / max 122.2440, expressed in 1725 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155856	5.8803	1582
155857	2.9573	1145
155855	0.6544	411
155854	0.0867	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.10	gold quality
right lobe of thyroid gland	UBERON:0001119	90.90	gold quality
left lobe of thyroid gland	UBERON:0001120	90.13	gold quality
left testis	UBERON:0004533	89.82	gold quality
right testis	UBERON:0004534	89.67	gold quality
ventricular zone	UBERON:0003053	89.52	gold quality
thyroid gland	UBERON:0002046	89.33	gold quality
testis	UBERON:0000473	87.55	gold quality
adenohypophysis	UBERON:0002196	87.18	gold quality
cortical plate	UBERON:0005343	86.53	gold quality
stromal cell of endometrium	CL:0002255	86.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.23	gold quality
pituitary gland	UBERON:0000007	86.07	gold quality
bronchial epithelial cell	CL:0002328	85.54	gold quality
left ovary	UBERON:0002119	85.24	gold quality
sural nerve	UBERON:0015488	85.15	gold quality
right ovary	UBERON:0002118	84.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.42	gold quality
epithelium of bronchus	UBERON:0002031	84.32	gold quality
ganglionic eminence	UBERON:0004023	83.96	gold quality
cerebellar hemisphere	UBERON:0002245	83.82	gold quality
body of uterus	UBERON:0009853	83.73	gold quality
endocervix	UBERON:0000458	83.67	gold quality
cerebellar cortex	UBERON:0002129	83.59	gold quality
bronchus	UBERON:0002185	83.53	gold quality
metanephros cortex	UBERON:0010533	83.26	gold quality
right adrenal gland	UBERON:0001233	82.88	gold quality
right adrenal gland cortex	UBERON:0035827	82.65	gold quality
right lung	UBERON:0002167	82.39	gold quality
upper lobe of left lung	UBERON:0008952	82.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.79
E-MTAB-6142	no	96.68
E-GEOD-75367	no	71.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting IFT140, 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-3064-3P	100.00	70.09	1254
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-4703-3P	96.68	68.61	545
HSA-MIR-4791	96.51	67.76	659
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-4259	95.68	65.25	582
HSA-MIR-1538	85.86	60.08	75

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression. (PMID:22282595)
• IFT140 mutations were identified in Mainzer-Saldino syndrome. IFT140 plays a role in proper development and function of ciliated cells. (PMID:22503633)
• present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy (PMID:23418020)
• Genetic analysis revealed both to harbor recessive mutations in IFT140, a cilium gene recently associated with the skeletal ciliopathy conorenal syndrome. (PMID:24698627)
• Identification of IFT140 variants in multiple unrelated non-syndromic Leber congenital amaurosis and retinitis pigmentosa. (PMID:26216056)
• Recessive IFT140 mutations cause a severe congenital retinal dystrophy with high hyperopia and often early photophilia. Developmental delay is common but not universal and not all patients have obvious extraocular findings. (PMID:26359340)
• This study highlights the phenotype of nonsyndromic RP due to mutations in IFT140 with milder retinal dystrophy than that associated with the syndromic disease. (PMID:26968735)
• We provide the first description of an Opitz trigonocephaly C syndrome (OTCS) phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy (PMID:27874174)
• A maternally inherited homozygous biallelic mutation altering the exon 6 splice donor site in IFT140 gene causes Mainzer-Saldino syndrome. (PMID:28724397)
• Compound heterozygous variants in IFT140 NM_014714.3: c.4182G>C p.(Thr1394Thr) and c.212C>T p.(Pro71Leu) were identified, and confirmed by Sanger sequencing. (PMID:29111861)
• we demonstrated the implication of structural variations in IFT140-related diseases expanding its mutation spectrum. We also provide evidences for a unique genomic event mediated by an Alu-Alu recombination occurring on a shared haplotype. (PMID:29688594)
• Role of IFT140 in Osteogenesis of Adult Mice Long Bone (PMID:31034313)
• This study for the first time reported IFT140 variants that cause infertility in humans. (PMID:31397098)
• Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype. (PMID:34890546)
• Monoallelic Loss-of-Function IFT140 Pathogenic Variants Cause Autosomal Dominant Polycystic Kidney Disease: A Confirmatory Study With Suspicion of an Additional Cardiac Phenotype. (PMID:37844724)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ift140	ENSDARG00000031886
mus_musculus	Ift140	ENSMUSG00000024169
rattus_norvegicus	Ift140	ENSRNOG00000016545
drosophila_melanogaster	rempA	FBGN0260933
caenorhabditis_elegans		WBGENE00000490

Paralogs (1): IFT172 (ENSG00000138002)

Protein

Protein identifiers

Intraflagellar transport protein 140 homolog — Q96RY7 (reviewed: Q96RY7)

Alternative names: WD and tetratricopeptide repeats protein 2

All UniProt accessions (5): Q96RY7, H3BNC5, H3BTA5, I3L0Y8, J3KPW0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs). Plays a pivotal role in proper development and function of ciliated cells through its role in ciliogenesis and/or cilium maintenance. Required for the development and maintenance of the outer segments of rod and cone photoreceptor cells. Plays a role in maintenance and the delivery of opsin to the outer segment of photoreceptor cells.

Subunit / interactions. Component of the IFT complex A (IFT-A). IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts (via C-terminal region) with IFT122 (via C-terminal region). Interacts with TTC25. Interacts with TTC21A.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Cell projection. Cilium.

Disease relevance. Short-rib thoracic dysplasia 9 with or without polydactyly (SRTD9) [MIM:266920] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. SRTD9 is characterized by phalangeal cone-shaped epiphyses, chronic renal disease, nearly constant retinal dystrophy, and mild radiographic abnormality of the proximal femur. Occasional features include short stature, cerebellar ataxia, and hepatic fibrosis. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 80 (RP80) [MIM:617781] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP80 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Polycystic kidney disease 9 (PKD9) [MIM:621164] A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts may also occur in other organs, particularly the liver. PKD9 is a mild form characterized by a slowly progressive renal disease with onset in adulthood. Affected individuals have limited renal insufficiency and end-stage renal disease is rare. PKD9 inheritance is autosomal dominant with incomplete, age-dependent penetrance. Oligogenic inheritance is observed in some families. Disease susceptibility is associated with variants affecting the gene represented in this entry. Cranioectodermal dysplasia 5 (CED5) [MIM:621180] A form of cranioectodermal dysplasia, a disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described. CED5 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96RY7-1	1	yes
Q96RY7-2	2

RefSeq proteins (1): NP_055529* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR056154	Beta-prop_IFT140_1st	Domain
IPR056155	Beta-prop_IFT140_2nd	Domain
IPR056156	TPR_IF140_C	Domain
IPR056168	TPR_IF140/IFT172/WDR19	Domain

Pfam: PF23383, PF23385, PF24760, PF24762

UniProt features (218 total): strand 67, sequence variant 58, helix 57, repeat 16, turn 12, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8BBG	ELECTRON MICROSCOPY	3.5
8FGW	ELECTRON MICROSCOPY	3.7
8FH3	ELECTRON MICROSCOPY	4.3
8BBF	ELECTRON MICROSCOPY	8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RY7-F1	80.48	0.18

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 (2): 360, 1443

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: 626 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, MORF_RAGE, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (17): determination of left/right symmetry (GO:0007368), heart development (GO:0007507), regulation of smoothened signaling pathway (GO:0008589), neural tube patterning (GO:0021532), embryonic camera-type eye development (GO:0031076), intraciliary retrograde transport (GO:0035721), photoreceptor cell outer segment organization (GO:0035845), embryonic digit morphogenesis (GO:0042733), embryonic cranial skeleton morphogenesis (GO:0048701), cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), regulation of cilium assembly (GO:1902017), non-motile cilium assembly (GO:1905515), embryonic brain development (GO:1990403), cell projection organization (GO:0030030), limb morphogenesis (GO:0035108), intraciliary transport (GO:0042073)

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

GO Cellular Component (15): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), centrosome (GO:0005813), centriole (GO:0005814), cilium (GO:0005929), axoneme (GO:0005930), intraciliary transport particle A (GO:0030991), photoreceptor connecting cilium (GO:0032391), ciliary basal body (GO:0036064), ciliary tip (GO:0097542), cone photoreceptor outer segment (GO:0120199), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995), non-motile cilium (GO:0097730)

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	5
cilium	4
microtubule organizing center	3
embryonic organ development	2
cellular component organization	2
cilium organization	2
cilium assembly	2
intracellular membraneless organelle	2
intraciliary transport particle	2
determination of bilateral symmetry	1
left/right pattern formation	1
animal organ development	1
circulatory system development	1
smoothened signaling pathway	1
regulation of signal transduction	1
regionalization	1
neural tube development	1
camera-type eye development	1
intraciliary transport	1
photoreceptor cell development	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
embryonic skeletal system morphogenesis	1
cranial skeletal system development	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
protein localization to organelle	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	1
appendage morphogenesis	1
limb development	1
transport along microtubule	1
binding	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT140	IFT122	Q9HBG6	997
IFT140	WDR19	Q8NEZ3	997
IFT140	IFT43	Q96FT9	996
IFT140	WDR35	Q9P2L0	996
IFT140	TTC21B	Q7Z4L5	995
IFT140	IFT52	Q9Y366	903
IFT140	IFT88	Q13099	901
IFT140	IFT80	Q9P2H3	899
IFT140	IFT81	Q8WYA0	881
IFT140	IFT27	Q9BW83	862
IFT140	IFT20	Q8IY31	854
IFT140	IFT172	Q9UG01	841
IFT140	IFT22	Q9H7X7	800
IFT140	IFT57	Q9NWB7	796
IFT140	IFT46	Q9NQC8	776

IntAct

94 interactions, top by confidence:

A	B	Type	Score
WDR19	TULP3	psi-mi:“MI:0914”(association)	0.860
TULP3	WDR19	psi-mi:“MI:0915”(physical association)	0.860
TULP3	WDR19	psi-mi:“MI:0914”(association)	0.860
TULP3	TTC21B	psi-mi:“MI:0914”(association)	0.840
TTC21B	TULP3	psi-mi:“MI:0914”(association)	0.840
IFT122	WDR19	psi-mi:“MI:0914”(association)	0.800
TULP3	FOXK2	psi-mi:“MI:0914”(association)	0.790
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
IFT140	WDR19	psi-mi:“MI:0915”(physical association)	0.780
WDR19	IFT140	psi-mi:“MI:0915”(physical association)	0.780
IFT140	WDR19	psi-mi:“MI:0914”(association)	0.780
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
IFTAP	PLK1	psi-mi:“MI:0914”(association)	0.640
TULP3	GGPS1	psi-mi:“MI:0914”(association)	0.640
IFT43	TTC21B	psi-mi:“MI:0914”(association)	0.530
IFT122	DNAJA2	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
TULP3	HSPG2	psi-mi:“MI:0914”(association)	0.530
IFTAP	WDR19	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
TULP2	LONP1	psi-mi:“MI:0914”(association)	0.530
IFT122	CDC7	psi-mi:“MI:0914”(association)	0.510
IFT140	ACSL3	psi-mi:“MI:0914”(association)	0.510

BioGRID (70): IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Two-hybrid), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), IFT43 (Affinity Capture-MS), TULP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HX76, A0JP70, A4IG72, A7E3S5, A7Z052, D3ZW91, E9PY46, P57081, Q05B17, Q0P5H9, Q15061, Q32P44, Q3SZD4, Q3U821, Q499N3, Q4VBE8, Q5BK48, Q5F3K4, Q5RB07, Q5RBH8, Q5RD06, Q5XFW6, Q68EI0, Q6DFC6, Q6KAU8, Q6PFM9, Q6PGF3, Q6ZQL4, Q7ZVF0, Q7ZVR1, Q7ZY78, Q8BH57, Q8C5V5, Q8IWA0, Q8N0Z6, Q8NA23, Q8NAA4, Q8VC03, Q969R8, Q96KV7

Diamond homologs: A8BAF1, E9PY46, Q96RY7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IFT140	“form complex”	“ITF complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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	6	22.3×	7e-05
Hedgehog ‘off’ state	5	16.5×	2e-03
Regulation of PLK1 Activity at G2/M Transition	5	11.8×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary retrograde transport	6	85.3×	2e-08
protein localization to cilium	7	35.5×	3e-07
protein folding	8	10.5×	2e-04
cilium assembly	8	7.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2258 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	97
Likely pathogenic	101
Uncertain significance	938
Likely benign	739
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069327	NM_014714.4(IFT140):c.2677G>T (p.Glu893Ter)	Pathogenic
1071413	NM_014714.4(IFT140):c.1501C>T (p.Arg501Ter)	Pathogenic
1073514	NM_014714.4(IFT140):c.54del (p.Ser19fs)	Pathogenic
1184606	NM_014714.4(IFT140):c.1422_1423insAA (p.Arg475fs)	Pathogenic
1213850	NM_014714.4(IFT140):c.635-1G>C	Pathogenic
1298391	NM_014714.4(IFT140):c.2214_2217del (p.Asp738fs)	Pathogenic
1325702	NM_014714.4(IFT140):c.1039C>T (p.Arg347Ter)	Pathogenic
1328235	NM_014714.4(IFT140):c.3109C>T (p.Gln1037Ter)	Pathogenic
1358543	NM_014714.4(IFT140):c.3691_3692del (p.Thr1231fs)	Pathogenic
1375858	NM_014714.4(IFT140):c.1992_2005dup (p.Thr669fs)	Pathogenic
1383614	NM_014714.4(IFT140):c.2934C>A (p.Tyr978Ter)	Pathogenic
1391821	NM_014714.4(IFT140):c.3727C>T (p.Gln1243Ter)	Pathogenic
1391918	NM_014714.4(IFT140):c.3672_3673del (p.Leu1225fs)	Pathogenic
1408932	NM_014714.4(IFT140):c.3489del (p.Asn1163fs)	Pathogenic
1449273	NC_000016.9:g.(?1568197)(1570829_?)dup	Pathogenic
1451353	NM_014714.4(IFT140):c.490G>T (p.Glu164Ter)	Pathogenic
1453885	NC_000016.9:g.(?1607916)(1608155_?)del	Pathogenic
1455247	NM_014714.4(IFT140):c.3640C>T (p.Gln1214Ter)	Pathogenic
1458035	NC_000016.9:g.(?1621388)(1621555_?)del	Pathogenic
1458870	NC_000016.9:g.(?1633295)(1637325_?)del	Pathogenic
1458986	NM_014714.4(IFT140):c.1795dup (p.Ile599fs)	Pathogenic
1459528	NM_014714.4(IFT140):c.1525-2A>T	Pathogenic
1905580	NM_014714.4(IFT140):c.2483del (p.Gly828fs)	Pathogenic
196180	NM_014714.4(IFT140):c.3991C>T (p.Gln1331Ter)	Pathogenic
1975503	NC_000016.10:g.1602592del	Pathogenic
1976558	NM_014714.4(IFT140):c.889G>T (p.Glu297Ter)	Pathogenic
1989768	NM_014714.4(IFT140):c.2411G>A (p.Trp804Ter)	Pathogenic
2003276	NM_014714.4(IFT140):c.3313C>T (p.Gln1105Ter)	Pathogenic
2027672	NM_014714.4(IFT140):c.169del (p.His57fs)	Pathogenic
2111485	NM_014714.4(IFT140):c.3502G>T (p.Glu1168Ter)	Pathogenic

SpliceAI

7743 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1518207:AGG:A	donor_gain	1.0000
16:1518215:CCGT:C	donor_gain	1.0000
16:1518229:T:TA	donor_gain	1.0000
16:1518233:T:TA	donor_gain	1.0000
16:1519397:AGCAT:A	donor_gain	1.0000
16:1519398:G:C	donor_gain	1.0000
16:1519411:T:A	donor_gain	1.0000
16:1519915:T:TA	donor_gain	1.0000
16:1520046:ACC:A	acceptor_loss	1.0000
16:1520047:CC:C	acceptor_loss	1.0000
16:1520048:C:CA	acceptor_loss	1.0000
16:1520125:CTGCA:C	donor_loss	1.0000
16:1520126:TGCA:T	donor_loss	1.0000
16:1520127:GCACC:G	donor_loss	1.0000
16:1520128:CACCT:C	donor_loss	1.0000
16:1520129:ACCTG:A	donor_loss	1.0000
16:1520148:AAAAG:A	donor_gain	1.0000
16:1520177:C:A	donor_gain	1.0000
16:1520340:TGGC:T	acceptor_gain	1.0000
16:1520343:CCTAG:C	acceptor_loss	1.0000
16:1520344:C:CC	acceptor_gain	1.0000
16:1520598:TCAC:T	donor_loss	1.0000
16:1520599:CACC:C	donor_loss	1.0000
16:1520600:A:AC	donor_gain	1.0000
16:1520601:C:CC	donor_gain	1.0000
16:1520601:C:CG	donor_loss	1.0000
16:1520601:CCTT:C	donor_gain	1.0000
16:1520631:T:TA	donor_gain	1.0000
16:1520804:TGATA:T	acceptor_gain	1.0000
16:1520805:GATA:G	acceptor_gain	1.0000

AlphaMissense

9657 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1520243:A:G	L1254P	0.999
16:1520252:G:T	A1251D	0.999
16:1520255:G:T	A1250D	0.999
16:1520639:G:T	A1208D	0.999
16:1519993:C:G	A1310P	0.998
16:1520247:A:C	Y1253D	0.998
16:1520253:C:G	A1251P	0.998
16:1520256:C:G	A1250P	0.998
16:1520291:G:T	A1238E	0.998
16:1520322:A:G	S1228P	0.998
16:1520330:A:G	L1225P	0.998
16:1520619:C:G	A1215P	0.998
16:1520675:G:T	A1196E	0.998
16:1520135:G:T	A1290D	0.997
16:1520149:A:C	F1285L	0.997
16:1520149:A:T	F1285L	0.997
16:1520151:A:G	F1285L	0.997
16:1520187:A:C	Y1273D	0.997
16:1520327:A:G	L1226P	0.997
16:1520334:C:G	A1224P	0.997
16:1568232:G:C	S585R	0.997
16:1568232:G:T	S585R	0.997
16:1568234:T:G	S585R	0.997
16:1520136:C:G	A1290P	0.996
16:1520150:A:G	F1285S	0.996
16:1520252:G:A	A1251V	0.996
16:1520293:G:C	F1237L	0.996
16:1520293:G:T	F1237L	0.996
16:1520295:A:G	F1237L	0.996
16:1520628:A:C	Y1212D	0.996

dbSNP variants (sampled 300 via entrez): RS1000032230 (16:1537767 G>A), RS1000054343 (16:1578071 A>C), RS1000054839 (16:1550499 G>C,T), RS1000078187 (16:1560002 C>T), RS1000078593 (16:1602396 C>T), RS1000084062 (16:1537923 G>T), RS1000102392 (16:1568646 G>A), RS1000147192 (16:1595850 C>G,T), RS1000188092 (16:1612073 G>A), RS1000194311 (16:1535011 C>A), RS1000199074 (16:1579108 A>G), RS1000225831 (16:1573029 G>A), RS1000240905 (16:1596000 G>A), RS1000250067 (16:1533725 G>A), RS1000292750 (16:1596201 C>G,T)

Disease associations

OMIM: gene MIM:614620 | disease phenotypes: MIM:266920, MIM:617781, MIM:204000, MIM:208500, MIM:268000, MIM:621164, MIM:258850, MIM:173900, MIM:256100, MIM:602482, MIM:601631, MIM:621180, MIM:218330

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant polycystic kidney disease	Definitive	Autosomal dominant
IFT140-related recessive ciliopathy	Definitive	Autosomal recessive
short-rib thoracic dysplasia 9 with or without polydactyly	Definitive	Autosomal recessive
retinitis pigmentosa 80	Strong	Autosomal recessive
cystic kidney disease	Strong	Autosomal dominant
Jeune syndrome	Supportive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
autosomal dominant polycystic kidney disease	Definitive	AD
IFT140-related recessive ciliopathy	Definitive	AR

Mondo (25): short-rib thoracic dysplasia 9 with or without polydactyly (MONDO:0009964), retinitis pigmentosa 80 (MONDO:0054708), inherited retinal dystrophy (MONDO:0019118), cystic kidney disease (MONDO:0002473), Leber congenital amaurosis (MONDO:0018998), asphyxiating thoracic dystrophy 1 (MONDO:0008831), optic atrophy (MONDO:0003608), retinitis pigmentosa (MONDO:0019200), myoepithelial tumor (MONDO:0002380), cleft palate (MONDO:0016064), retinal disorder (MONDO:0005283), polycystic kidney disease 9, susceptibility to (MONDO:0976267), orofaciodigital syndrome III (MONDO:0009793), Jeune syndrome (MONDO:0018770), microcephaly (MONDO:0001149)

Orphanet (14): Saldino-Mainzer syndrome (Orphanet:140969), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Jeune syndrome (Orphanet:474), Retinitis pigmentosa (Orphanet:791), Cleft palate (Orphanet:2014), Orofaciodigital syndrome type 3 (Orphanet:2752), Autosomal dominant polycystic kidney disease (Orphanet:730), Retinal ciliopathy due to mutation in the retinitis pigmentosa-1 gene (Orphanet:156168), Nephronophthisis (Orphanet:655), Axenfeld-Rieger syndrome (Orphanet:782), Rieger anomaly (Orphanet:91483), Cranioectodermal dysplasia (Orphanet:1515), Joubert syndrome with Jeune asphyxiating thoracic dystrophy (Orphanet:397715)

HPO phenotypes

245 total (30 of 245 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000073	Ureteral duplication
HP:0000074	Ureteropelvic junction obstruction
HP:0000083	Renal insufficiency
HP:0000090	Nephronophthisis
HP:0000093	Proteinuria
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000112	Nephropathy
HP:0000113	Polycystic kidney dysplasia
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000191	Accessory oral frenulum
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000307	Pointed chin
HP:0000308	Microretrognathia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002949_19	Epilepsy and lamotrigine-induced maculopapular eruptions	3.000000e-10
GCST005194_188	Coronary artery disease	8.000000e-06
GCST010866_66	Coronary artery disease	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001253	maculopapular eruption

MeSH disease descriptors (15)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D052177	Kidney Diseases, Cystic	C12.050.351.968.419.403; C12.200.777.419.403; C12.950.419.403
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009208	Myoepithelioma	C04.557.435.585
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C535535	Iridogoniodysgenesis type1 (supp.)
C537571	Jeune syndrome (supp.)
C557817	Orofaciodigital syndrome 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	3
sodium arsenite	increases abundance, affects splicing, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, decreases methylation	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
bufotalin	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
benzo(e)pyrene	increases methylation	1
mono(2-ethyl-5-oxohexyl)phthalate	increases abundance, increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
mono(2-ethyl-5-hydroxyhexyl) phthalate	increases methylation, increases abundance	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
mono-isobutyl phthalate	increases abundance, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases abundance, increases methylation	1
Smoke	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414440	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT03273413	PHASE4	ACTIVE_NOT_RECRUITING	Statin Therapy in Patients With Early Stage ADPKD
NCT03949894	PHASE4	COMPLETED	Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00309283	PHASE3	COMPLETED	Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study
NCT00346918	PHASE3	COMPLETED	Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT00428948	PHASE3	COMPLETED	Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01022424	PHASE3	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2) [Extension of Study 156-05-002]
NCT01214421	PHASE3	COMPLETED	Tolvaptan Extension Study in Participants With ADPKD
NCT01377246	PHASE3	COMPLETED	Somatostatin In Patients With Autosomal Dominant Polycystic Kidney Disease And Moderate To Severe Renal Insufficiency
NCT01616927	PHASE3	UNKNOWN	Study of Lanreotide to Treat Polycystic Kidney Disease
NCT01853553	PHASE3	COMPLETED	Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02115659	PHASE3	UNKNOWN	Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02134899	PHASE3	COMPLETED	The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients
NCT02160145	PHASE3	COMPLETED	Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
NCT02964273	PHASE3	COMPLETED	Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
NCT03764605	PHASE3	UNKNOWN	Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT03918447	PHASE3	TERMINATED	A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
NCT04064346	PHASE3	TERMINATED	Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT04152837	PHASE3	TERMINATED	Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
NCT04939935	PHASE3	RECRUITING	Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
NCT05373264	PHASE3	RECRUITING	HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT04705051	PHASE3	TERMINATED	Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
NCT00841568	PHASE2	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001]
NCT01210560	PHASE2	COMPLETED	Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
NCT01336972	PHASE2	COMPLETED	Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)