KIF7 Acts as both a negative and positive regulator of sonic hedgehog (Shh) pathway, acting downstream of SMO. Negatively regulates the pathway by preventing inappropriate activation of the transcriptional activator GLI2 in the absence of ligand. Positively regulates the pathway by preventing the processing of the transcription factor GLI3 into its repressor form. Required for efficient localization of GLI3 to cilia in response to Shh. Affects microtubular dynamics and acts as a ciliary motor. Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and hydrolethalus syndrome among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome influence the clinical outcome. Primary ciliopathy loci can be modulated by pathogenic lesions in other ciliary genes to either exacerbate overall severity or induce specific endophenotypes. KIF7 may be causally associated with diverse ciliopathies, and also acts as a modifier gene across the ciliopathy spectrum. Defects in KIF7 may be a cause of Bardet-Biedl syndrome (BBS). A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. 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. Heterozygous missense mutations in KIF7 may genetically interact with other BBS genes and contribute to disease manifestation and severity. Defects in KIF7 are the cause of hydrolethalus syndrome type 2 (HLS2). HLS2 is an embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Duplication of the hallux is a common finding. Defects in KIF7 are the cause of acrocallosal syndrome (ACLS). ACLS is a syndrome that is characterized by postaxial polydactyly, hallux duplication, macrocephaly and absence of the corpus callosum, usually with severe developmental delay. Defects in KIF7 are the cause of Joubert syndrome type 12 (JBTS12). JBTS12 is a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Defects in KIF7 may be a cause of Pallister-Hall syndrome (PHS). An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia. Belongs to the kinesin-like protein family. KIF27 subfamily. Note: This description may include information from UniProtKB.
Protein type: Microtubule-binding; Motor
Chromosomal Location of Human Ortholog: 1q31
Cellular Component:  ciliary basal body; cilium; kinesin complex; microtubule
Molecular Function:  ATP binding; ATPase activity; identical protein binding; microtubule binding; microtubule motor activity
Biological Process:  aorta development; cardiac septum development; coronary vasculature development; microtubule-based movement; negative regulation of smoothened signaling pathway; positive regulation of smoothened signaling pathway
Reference #:  D4A9P0 (UniProtKB)
Alt. Names/Synonyms: Kif7; Kinesin family member 7
Gene Symbols: Kif7
Molecular weight: 150,578 Da
Basal Isoelectric point: 6.44  Predict pI for various phosphorylation states
CST Pathways:  Hedgehog Signaling
Select Structure to View Below

KIF7

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  BioGPS  |  Pfam  |  Phospho.ELM  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein