Specific monogenic disorders caused by variants affecting the function of KIF genes
| Kinesin family | KIF gene | Associated phenotypes, OMIM | Clinical description | Cytogenetic location | Inheritance | Variant type |
| Kinesin 1 | KIF5A | Spastic paraplegia type 10, #604 187 | Gait abnormalities, lower limb hyper-reflexia, spasticity and weakness; upper limb spasticity and bladder dysfunction frequent; sensory disturbances common; variable phenotype, also including intellectual disability | 12q13.3 | AD | Missense variants Motor domain |
| Neonatal intractable myoclonus, #617 235 | Nystagmus, optic nerve pallor, myoclonus seizures, clonic seizures, developmental arrest, delayed myelination, athetoid and choreiform movements | 12q13.3 | AD | Stop-loss frameshift variants Cargo-binding domain | ||
| KIF5C | Cortical dysplasia, complex, with other brain malformations 2, #615 282 | Delayed psychomotor development, foetal akinesia, spastic tetraplegia, seizures, malformations of cortical development and arthrogryposis | 2q23.1-q23.2 | AD | Missense variants Microtubule-binding domain | |
| KLC2 | Spastic paraplegia, optic atrophy, and neuropathy, #609 541 | Congenital optic atrophy, early-onset progressive spastic paraplegia, hyper-reflexia, dysarthria, distal axonal motor and sensory peripheral neuropathy | 11q13.2 | AR | Missense variants Motor domain | |
| Kinesin 2 | KIF3C | Sporadic infantile spasm syndrome58 | Clinical spasms with ictal electrodecrement, usually occurring before the age of 1 year and frequently associated with cognitive impairment | 2p23.3 | Candidate gene/AD | Missense variant Coiled-coil region |
| Kinesin 3 | KIF1A | Hereditary sensory neuropathy type IIC, #614 213 | Progressive sensory neuropathy, areflexia, hyporeflexia and developmental delay | 2q37.3 | AR | Truncating variants |
| Mental retardation, autosomal dominant 9, #614 255 | Developmental delay, intellectual disability, microcephaly, cerebellar atrophy, spasticity, possible seizures, hypotonia and clubfoot | 2q37.3 | AD | Missense variants Motor domain | ||
| Spastic paraplegia type 30, #610 357 | Lower limb spasticity, spastic gait, hyper-reflexia, lower limb muscle atrophy and weakness | 2q37.3 | AR | Missense variants Motor domain | ||
| KIF1B | Charcot-Marie-Tooth disease, axonal, type 2a1, #118 210 | Distal limb weakness and atrophy due to peripheral neuropathy, foot drop, hyporeflexia, areflexia, pes cavus and hammer toes; childhood onset of the disease | 1p36.22 | AD | Loss-of-function variants Motor domain | |
| KIF1BP / KIAA1279 | Goldberg-Shprintzen megacolon syndrome, #609 460 | Intellectual disability, microcephaly and dysmorphic facial features; Hirschsprung disease and/or gyral abnormalities of the brain in most patients; megalocornea or urogenital anomalies may also be present | 10q22.1 | AR | Nonsense variants | |
| KIF1C | Spastic ataxia type 2, #611 302 | Dysarthria, cerebellar gait ataxia, dysmetria, tremor, spasticity of the lower limbs, hyper-reflexia and distal muscle atrophy; onset in teenage years | 17p13.2 | AR | Nonsense/truncating variants/whole-gene deletion | |
| KIF14 | Meckel syndrome 12, #616 258 | IUGR, corpus callosum agenesis, cerebral and cerebellar hypoplasia, flexion arthrogryposis, renal agenesis and microcephaly | 1q32.1 | AR | Truncating variants | |
| Primary microcephaly type 20, #617 914 | Microcephaly, ID, autistic features; highly variable severity | 1q32.1 | AR | See table 2 for details. | ||
| KIF16B | Novel autosomal recessive ID syndrome49 | Facial dysmorphism, microcephaly, hypospadias and chordae, intellectual disability, seizures, brain atrophy and thinning of the corpus callosum | 20p12.1 | AR | Missense variants PX domain | |
| Kinesin 4 | KIF7 | Acrocallosal syndrome, #200 990 | Severe intellectual disability, postaxial polydactyly, hallux duplication, macrocephaly and absence of the corpus callosum | 15q26.1 | AR | Frameshift/nonsense variants Throughout the gene |
| Joubert syndrome 12, #200 990 | ID, molar tooth sign on brain MRI, ataxia, agenesis of the corpus callosum, hypertelorism, triangular mouth, downslanting palpebral fissures, low-set ears, prominent forehead and polydactyly | 15q26.1 | AR | Truncating variants/non-sense mediated decay | ||
| Al-Gazali-Bakalinova syndrome, #607 131 | Macrocephaly, frontal bossing, hypertelorism, flattening of the malar region, low-set ears, pectus excavatum and carinatum, spindle-shaped fingers with interdigital soft-tissue webbing, clinodactyly, genu valgum, swelling of the joints, dysplasia of the epiphyses of the long bones, agenesis of the corpus callosum and frontotemporal brain atrophy | 15q26.1 | AR | Missense variants Structural maintenance of chromosomes domain | ||
| Hydrolethalus syndrome 2, # 614 120 | Lethal developmental disorder: hydrocephaly, arhinencephaly, upper limb postaxial polydactyly, hallux duplication and molar tooth sign on MRI | 15q26.1 | AR | Microdeletion Coiled-coil region | ||
| KIF4A | Mental retardation, X-linked 100, #300 922 | Intellectual disability, seizures and mild facial dysmorphisms | Xq13.1 | XLR | In-frame deletion, splicing affected | |
| Isolated hydrocephalus11 | Hydrocehalus internus at 22 weeks of gestation | Xq13.1 | Candidate gene/XLR | Missense variant Coiled-coil domain | ||
| KIF21A | Fibrosis of extraocular muscles, congenital 1, #135 700 | Ptosis, hypotropic strabismus, fibrosis of extraocular muscles and compensatory backward tilt to the head | 12q12 | AD | Missense variants Stalk domain | |
| Fibrosis of extraocular muscles,congenital, 3B, #135 700 | Eyes in neutral primary position, residual upgaze and absence of ptosis | 12q12 | AD | Missense variants Stalk domain | ||
| Kinesin 5 | KIF11 | Microcephaly with or without chorioretinopathy, lymphoedema or mental retardation, #152 950. | Microcephaly, developmental delay, characteristic facial phenotype, chorioretinopathy, retinal folds and congenital lymphoedema | 10q23.33 | AD | Truncating variants |
| Kinesin 7 | KIF10/ CENPE | Microcephaly 13, primary autosomal recessive, #616 051 | Microcephaly, poor overall growth, developmental delay, dysmorphic facial features, severely simplified gyral pattern with partial agenesis of the corpus callosum and cerebellar hypoplasia | 4q24 | AR | Missense variants Coiled-coil region |
| Kinesin 10 | KIF22 | Spondyloepimetaphyseal dysplasia with joint laxity, type 2, #603 546 | Short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalised ligamentous laxity and mild spinal deformity | 16p11.2 | AD | Missense variants Kinesin motor domain |
| Kinesin 11 | KIF26B | Autosomal dominant spinocerebellar ataxia59 | Spasticity and gait/limb ataxia and very slow progression. | 1q44 | AD | Missense variants Tail region |
| Pontocerebellar hypoplasia with arthrogryposis50 | Progressive microcephaly, right germinolytic cyst, thinned corpus callosum, dysmorphic facial features, camptodactyly, congenital dislocations of both hips, congenital vertical talus (rocker-bottom feet), arthrogryposis of upper extremities and myoclonic seizures | 1q44 | Candidate gene/AD | Missense variant Kinesin motor domain | ||
| Kinesin 12 | KIF12 | Renal hypodysplasia52 | Congenital megabladder, renal hyopdysplasia and congenital vesicoureteral reflux | 9q32 | Candidate gene/AD | CNV (duplication) |
| High gamma-glutamyltransferase choleastasis60 | Neonatal choleastasis, paucity of bile ducts, mild renal pelvic abnormalities with unremarkable kidney function | 9q32 | AR | Truncating/missense variants Kinesin motor domain | ||
| KIF15 | Braddock-Carey-like syndrome54 | Microcephaly, congenital thrombocytopenia, Pierre-Robin sequence and agenesis of the corpus callosum | 3p21.31 | AR | Nonsense variants Coiled-coil domain | |
| Kinesin 13 | KIF2A | Cortical dysplasia, complex, with other brain malformations 3 (CDCBM3), #615 411 | Microcephaly, early-onset epilepsy and various malformations of cortical development, including agyria, posterior or frontal pachygyria, subcortical band heterotopia and thin corpus callosum; severe developmental delay, spastic paraplegia, persistent hyperplastic primary vitreous and microphthalmia | 5q12.1 | AD | Missense variants Kinesin motor domain |
Susceptibility loci are not included.
OMIM online mendelian inheritance of man, www.omim.org
AD, autosomal dominant; AR, autosomal recessive; CNV, copy number variant; IUGR, intrauterine growth retardation; PX, phox homology; XLR, X-linked recessive.