kinesin family member 7
The information on this page was automatically extracted from online scientific databases.
From NCBI Gene:
This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]
Essential for hedgehog signaling regulation: acts as both a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms (PubMed:21633164). Involved in the regulation of microtubular dynamics. Required for proper organization of the ciliary tip and control of ciliary localization of SUFU-GLI2 complexes (By similarity). Required for localization of GLI3 to cilia in response to Shh. Negatively regulates Shh signaling by preventing inappropriate activation of the transcriptional activator GLI2 in the absence of ligand. Positively regulates Shh signaling by preventing the processing of the transcription factor GLI3 into its repressor form. In keratinocytes, promotes the dissociation of SUFU-GLI2 complexes, GLI2 nuclear translocation and Shh signaling activation (By similarity). Involved in the regulation of epidermal differentiation and chondrocyte development.
From NCBI Gene:
- Macrocephaly with multiple epiphyseal dysplasia and distinctive facies
- Hydrolethalus syndrome 2
- Acrocallosal syndrome, Schinzel type
Hydrolethalus syndrome 2 (HLS2): 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. [MIM:614120]
Joubert syndrome 12 (JBTS12): 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. [MIM:200990]
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. [MIM:209900]
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. [MIM:146510]
Al-Gazali-Bakalinova syndrome (AGBK): An autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance. [MIM:607131]
Acrocallosal syndrome (ACLS): A syndrome characterized by hypogenesis or agenesis of the corpus callosum. Clinical features include postaxial polydactyly, hallux duplication, macrocephaly, craniofacial abnormalities, severe developmental delay and mental retardation. [MIM:200990]
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.