Table 1

Specific monogenic disorders caused by variants affecting the function of KIF genes

Kinesin family KIF geneAssociated phenotypes, OMIMClinical descriptionCytogenetic locationInheritanceVariant type
Kinesin 1 KIF5A Spastic paraplegia type 10, #604 187Gait abnormalities, lower limb hyper-reflexia, spasticity and weakness; upper limb spasticity and bladder dysfunction frequent; sensory disturbances common; variable phenotype, also including intellectual disability12q13.3ADMissense variants
Motor domain
Neonatal intractable myoclonus, #617 235Nystagmus, optic nerve pallor, myoclonus seizures, clonic seizures, developmental arrest, delayed myelination, athetoid and choreiform movements12q13.3ADStop-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 arthrogryposis2q23.1-q23.2ADMissense 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 neuropathy11q13.2ARMissense 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 impairment2p23.3Candidate gene/ADMissense variant
Coiled-coil region
Kinesin 3 KIF1A Hereditary sensory neuropathy type IIC, #614 213Progressive sensory neuropathy, areflexia, hyporeflexia and developmental delay2q37.3ARTruncating variants
Mental retardation, autosomal dominant 9, #614 255Developmental delay, intellectual disability, microcephaly, cerebellar atrophy, spasticity, possible seizures, hypotonia and clubfoot2q37.3ADMissense variants
Motor domain
Spastic paraplegia type 30, #610 357Lower limb spasticity, spastic gait, hyper-reflexia, lower limb muscle atrophy and weakness2q37.3ARMissense variants
Motor domain
KIF1B Charcot-Marie-Tooth disease, axonal, type 2a1, #118 210Distal limb weakness and atrophy due to peripheral neuropathy, foot drop, hyporeflexia, areflexia, pes cavus and hammer toes; childhood onset of the disease1p36.22ADLoss-of-function variants
Motor domain
Goldberg-Shprintzen megacolon syndrome, #609 460Intellectual 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 present10q22.1ARNonsense variants
KIF1C Spastic ataxia type 2, #611 302Dysarthria, cerebellar gait ataxia, dysmetria, tremor, spasticity of the lower limbs, hyper-reflexia and distal muscle atrophy; onset in teenage years17p13.2ARNonsense/truncating variants/whole-gene deletion
KIF14 Meckel syndrome 12, #616 258IUGR, corpus callosum agenesis, cerebral and cerebellar hypoplasia, flexion arthrogryposis, renal agenesis and microcephaly1q32.1ARTruncating variants
Primary microcephaly type 20, #617 914Microcephaly, ID, autistic features; highly variable severity1q32.1ARSee 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 callosum20p12.1ARMissense variants
PX domain
Kinesin 4 KIF7 Acrocallosal syndrome, #200 990Severe intellectual disability, postaxial polydactyly, hallux duplication, macrocephaly and absence of the corpus callosum15q26.1ARFrameshift/nonsense variants
Throughout the gene
Joubert syndrome 12, #200 990ID, molar tooth sign on brain MRI, ataxia, agenesis of the corpus callosum, hypertelorism, triangular mouth, downslanting palpebral fissures, low-set ears, prominent forehead and polydactyly15q26.1ARTruncating variants/non-sense mediated decay
Al-Gazali-Bakalinova syndrome, #607 131Macrocephaly, 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 atrophy15q26.1ARMissense variants
Structural maintenance of chromosomes domain
Hydrolethalus syndrome 2, # 614 120Lethal developmental disorder: hydrocephaly, arhinencephaly, upper limb postaxial polydactyly, hallux duplication and molar tooth sign on MRI15q26.1ARMicrodeletion
Coiled-coil region
KIF4A Mental retardation, X-linked 100, #300 922Intellectual disability, seizures and mild facial dysmorphismsXq13.1XLRIn-frame deletion, splicing affected
Isolated hydrocephalus11 Hydrocehalus internus at 22 weeks of gestationXq13.1Candidate gene/XLRMissense variant
Coiled-coil domain
KIF21A Fibrosis of extraocular muscles, congenital 1, #135 700Ptosis, hypotropic strabismus, fibrosis of extraocular muscles and compensatory backward tilt to the head12q12ADMissense variants
Stalk domain
Fibrosis of extraocular muscles,congenital, 3B, #135 700Eyes in neutral primary position, residual upgaze and absence of ptosis12q12ADMissense 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 lymphoedema10q23.33ADTruncating variants
Kinesin 7 KIF10/
Microcephaly 13, primary autosomal recessive, #616 051Microcephaly, poor overall growth, developmental delay, dysmorphic facial features, severely simplified gyral pattern with partial agenesis of the corpus callosum and cerebellar hypoplasia4q24ARMissense variants
Coiled-coil region
Kinesin 10 KIF22 Spondyloepimetaphyseal dysplasia with joint laxity, type 2, #603 546Short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalised ligamentous laxity and mild spinal deformity16p11.2ADMissense variants
Kinesin motor domain
Kinesin 11 KIF26B Autosomal dominant spinocerebellar ataxia59 Spasticity and gait/limb ataxia and very slow progression.1q44ADMissense 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 seizures1q44Candidate gene/ADMissense variant
Kinesin motor domain
Kinesin 12 KIF12 Renal hypodysplasia52 Congenital megabladder, renal hyopdysplasia and congenital vesicoureteral reflux9q32Candidate gene/ADCNV (duplication)
High gamma-glutamyltransferase choleastasis60 Neonatal choleastasis, paucity of bile ducts, mild renal pelvic abnormalities with unremarkable kidney function9q32ARTruncating/missense variants
Kinesin motor domain
KIF15 Braddock-Carey-like syndrome54 Microcephaly, congenital thrombocytopenia, Pierre-Robin sequence and agenesis of the corpus callosum3p21.31ARNonsense variants
Coiled-coil domain
Kinesin 13 KIF2A Cortical dysplasia, complex, with other brain malformations 3 (CDCBM3), #615 411Microcephaly, 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 microphthalmia5q12.1ADMissense variants
Kinesin motor domain
  • Susceptibility loci are not included.

  • OMIM online mendelian inheritance of man,

  • AD, autosomal dominant; AR, autosomal recessive; CNV, copy number variant; IUGR, intrauterine growth retardation; PX, phox homology; XLR, X-linked recessive.