IFT140

IFT140
Identifiers
Aliases	IFT140, MZSDS, SRTD9, WDTC2, c305C8.4, c380F5.1, gs114, intraflagellar transport 140, RP80
External IDs	OMIM: 614620 MGI: 2146906 HomoloGene: 40979 GeneCards: IFT140
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p13.3 Start 1,510,427 bp[1] End 1,612,072 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 A3.3 Start 25,235,059 bp[2] End 25,318,469 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube right lobe of thyroid gland left lobe of thyroid gland anterior pituitary stromal cell of endometrium bronchial epithelial cell sural nerve ganglionic eminence canal of the cervix right adrenal gland Top expressed in spermatocyte spermatid seminiferous tubule blood external carotid artery internal carotid artery medullary collecting duct motor neuron cumulus cell ureter More reference expression data BioGPS n/a
Gene ontology Molecular function molecular function protein binding Cellular component cytoplasm ciliary basal body centrosome cell projection photoreceptor outer segment intraciliary transport particle A photoreceptor connecting cilium microtubule organizing center ciliary tip axoneme cytoskeleton cilium non-motile cilium Biological process renal system development cilium assembly limb morphogenesis intraciliary transport skeletal system morphogenesis photoreceptor cell outer segment organization neural tube patterning regulation of smoothened signaling pathway heart development determination of left/right symmetry cell projection organization retina development in camera-type eye protein localization to cilium regulation of cilium assembly intraciliary retrograde transport embryonic camera-type eye development intraciliary transport involved in cilium assembly embryonic digit morphogenesis embryonic cranial skeleton morphogenesis non-motile cilium assembly embryonic brain development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9742 106633 Ensembl ENSG00000187535 ENSMUSG00000024169 UniProt Q96RY7 E9PY46 RefSeq (mRNA) NM_014714 NM_134126 RefSeq (protein) NP_055529 NP_598887 Location (UCSC) Chr 16: 1.51 – 1.61 Mb Chr 17: 25.24 – 25.32 Mb PubMed search [3] [4]
Wikidata
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IFT140, Intraflagellar transport 140 homolog, is a protein that in humans is encoded by the IFT140 gene. The gene product forms a core component of IFT-A complex which is indipensible for retrograde intraflagellar transport within the primary cilium.^[5]

Clinical significance

Mutations in this gene have been associated to cases of skeletal ciliopathy called Mainzer Saldino Syndrome, characterised by skeletal developmental anomalies, retinal degeneration and a fibrocystic renal disease known as nephronophthisis.^[6][7][8] It has also been described in patients with Jeune Syndrome^[9] and isolated Lebers congenital amaurosis in the absence of other syndromic features.^[10]

Model organisms

An ENU derived mouse (cauli) carrying homozygous IFT140 alleles (c.2564T>A, p. I855K) was generated at the Murdoch Children's Research Institute in Melbourne, Australia.^[9] The cauli mouse presented with mid-gestational lethality, exencephaly, spina bifida, craniofacial dysmorphism, digital anomalies, cardiac anomalies and somite patterning defects.^[9] Ectopic hedgehog signalling was demonstrated by wholemount in situ hybridisation in the limb buds and abnormal morphology of the primary cilium within the limb bud was demonstrated by scanning electron microscopy.^[9]

A patient with Mainzer Saldino Syndrome carrying compound heterozygous variants in IFT140 had induced pluripotent stem cells reprogrammed and CRISPR gene corrected before differentiating both stem cell lines into kidney organoids for transcriptional comparison.^[8] Aside from validating the club shaped morphology of the primary cilia seen in the cauli mouse limb bud within the regenerated nephron tubules of the IFT140^{c.634G>A/c.2176C>G} organoids compared to the IFT140^WT/c.2176C>G, bulk RNA sequencing comparison demonstrated significant differences in gene pathways related to apicobasal polarity, cell-cell junctions and axonemal dynein assembly.^[8]

References