NEK1
Function
Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617).
Involvement in disease
Short-rib thoracic dysplasia 6 with or without polydactyly
SRTD6
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
None
The disease is caused by variants affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617).
Amyotrophic lateral sclerosis 24
ALS24
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Orofaciodigital syndrome 2
OFD2
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD2 is an autosomal recessive form characterized by cleft lip/palate, lobulated tongue with nodules, dental anomalies, maxillary hypoplasia, conductive hearing loss, polydactyly, syndactyly, brachydactyly, and mesomelic lower limb shortening.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Tissue Specificity
High fetal expression in the brain and kidney.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasm
- Associated with the pericentriolar material (PubMed:21211617). Localizes to centrosome during interphase and mitosis (By similarity). Translocated from cytoplasm to discrete nuclear foci at sites of DNA damage (PubMed:15604234).
Alternative names
KIAA1901, NEK1, Serine/threonine-protein kinase Nek1, Never in mitosis A-related kinase 1, Renal carcinoma antigen NY-REN-55, NimA-related protein kinase 1