NEK1

NIMA related kinase 1

Basic information

Region (hg38): 4:169369703-169612632

Links

ENSG00000137601 ∙ NCBI:4750 ∙ OMIM:604588 ∙ HGNC:7744 ∙ Uniprot:Q96PY6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short-rib thoracic dysplasia 6 with or without polydactyly (Definitive), mode of inheritance: AR
• amyotrophic lateral sclerosis, susceptibility to, 24 (Moderate), mode of inheritance: AD
• orofaciodigital syndrome type II (Supportive), mode of inheritance: AR
• short rib-polydactyly syndrome, Majewski type (Supportive), mode of inheritance: AR
• short-rib thoracic dysplasia 6 with or without polydactyly (Strong), mode of inheritance: AR
• amyotrophic lateral sclerosis, susceptibility to, 24 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis, susceptibility to, 24 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib thoracic dysplasia 6 with or without polydactyly	AR/Digenic	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	21211617; 22499340; 22795106; 22499340; 26945885; 27455347
Heterozygous (digenic) variants in both NEK1 and DYNC2H1 can result in disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEK1 gene.

• Short-rib thoracic dysplasia 6 with or without polydactyly (457 variants)
• not provided (194 variants)
• not specified (31 variants)
• Inborn genetic diseases (24 variants)
• NEK1-related condition (21 variants)
• Connective tissue disorder (19 variants)
• Motor neuron disease (18 variants)
• Amyotrophic lateral sclerosis, susceptibility to, 24 (10 variants)
• Short rib-polydactyly syndrome (5 variants)
• Amyotrophic lateral sclerosis, susceptibility to, 24;Short-rib thoracic dysplasia 6 with or without polydactyly (3 variants)
• Amyotrophic lateral sclerosis (2 variants)
• Asphyxiating thoracic dystrophy 1 (2 variants)
• Short-rib thoracic dysplasia 6 with or without polydactyly;Amyotrophic lateral sclerosis, susceptibility to, 24 (2 variants)
• Immunodeficiency;Lymphopenia;Cough;Cor triatriatum dexter (1 variants)
• Lymphopenia;Immunodeficiency;Cough;Cor triatriatum dexter (1 variants)
• Type IV short rib polydactyly syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	78	5	92
missense		4	197	14	2	217
nonsense	10	4	1			15
start loss						0
frameshift	11	6	3			20
inframe indel						0
splice donor/acceptor (+/-2bp)	1	7	1			9
splice region			18	16	1	35
non coding			28	86	76	190
Total	22	21	239	178	83

Highest pathogenic variant AF is 0.0000394

Variants in NEK1

This is a list of pathogenic ClinVar variants found in the NEK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-169393288-A-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Likely benign (Jan 13, 2018)
4-169393355-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 12, 2018)
4-169393448-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169393514-C-T		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 12, 2018)
4-169393675-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169393704-C-T		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169393752-A-T		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169393800-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Benign (Jan 13, 2018)
4-169393852-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169393869-A-G		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 12, 2018)
4-169393959-T-A		Short-rib thoracic dysplasia 6 with or without polydactyly	Benign (Apr 27, 2017)
4-169393973-A-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169394015-A-G		Short-rib thoracic dysplasia 6 with or without polydactyly	Benign (Jan 13, 2018)
4-169394016-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169394051-T-G		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169394156-T-A		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 12, 2018)
4-169394345-C-T		Short-rib thoracic dysplasia 6 with or without polydactyly	Benign (Jun 14, 2018)
4-169394354-G-A		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 13, 2018)
4-169394356-C-T		Short-rib thoracic dysplasia 6 with or without polydactyly	Benign (Jan 12, 2018)
4-169394403-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Jan 12, 2018)
4-169394521-T-C		Short-rib thoracic dysplasia 6 with or without polydactyly	Uncertain significance (Aug 17, 2023)
4-169394526-G-A		NEK1-related disorder	Likely benign (May 18, 2022)
4-169394533-A-C			Likely benign (Jan 16, 2020)
4-169394536-G-GA		Short-rib thoracic dysplasia 6 with or without polydactyly	Benign (Jul 08, 2021)
4-169394721-G-A			Benign (Jun 14, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEK1	protein_coding	protein_coding	ENST00000507142	34	219355

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.91e-25	0.841	124563	0	91	124654	0.000365

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	542	617	0.879	0.0000302	8416
Missense in Polyphen		154	207.39	0.74257		2943
Synonymous	-0.138	213	210	1.01	0.0000106	2303
Loss of Function	2.54	51	74.7	0.683	0.00000381	1004

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000764	0.000759
Ashkenazi Jewish	0.000100	0.0000993
East Asian	0.000354	0.000334
Finnish	0.0000993	0.0000928
European (Non-Finnish)	0.000454	0.000434
Middle Eastern	0.000354	0.000334
South Asian	0.000432	0.000425
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

• Function: 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). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}.
• Disease: DISEASE: Amyotrophic lateral sclerosis 24 (ALS24) [MIM:617892]: 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. {ECO:0000269|PubMed:26945885, ECO:0000269|PubMed:27455347}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0930

Intolerance Scores

• loftool: 0.968
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.2

Haploinsufficiency Scores

• pHI: 0.596
• hipred: N
• hipred_score: 0.492
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.329

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nek1
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; growth/size/body region phenotype; hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: nek1
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein phosphorylation;cellular response to DNA damage stimulus;cell cycle;peptidyl-tyrosine phosphorylation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;DNA damage response, detection of DNA damage;cell division;cilium assembly
• Cellular component: pericentriolar material;nucleus;cytoplasm;centrosome
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;kinase activity;metal ion binding;14-3-3 protein binding