NEK2

NIMA related kinase 2, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 1:211658657-211675630

Links

ENSG00000117650 ∙ NCBI:4751 ∙ OMIM:604043 ∙ HGNC:7745 ∙ Uniprot:P51955 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 67 (Limited), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 67 (Limited), mode of inheritance: AR
• retinitis pigmentosa 67 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 67	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	24043777

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEK2 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		1	1	44	6	52
missense		2	120	4	1	127
nonsense			11			11
start loss						0
frameshift		2	6			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)			4			4
splice region			5	5		10
non coding			1	14	4	19
Total	0	5	144	62	11

Variants in NEK2

This is a list of pathogenic ClinVar variants found in the NEK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-211663432-C-T			Uncertain significance (Mar 09, 2022)
1-211663444-C-G		not specified	Uncertain significance (May 26, 2024)
1-211663446-G-T			Uncertain significance (Aug 21, 2022)
1-211663447-T-C		not specified • Retinal dystrophy	Benign (Jan 31, 2024)
1-211663449-T-C			Uncertain significance (Aug 31, 2022)
1-211663457-A-G			Uncertain significance (Aug 24, 2022)
1-211663459-T-C			Likely benign (Jul 12, 2023)
1-211663464-A-C			Uncertain significance (Feb 28, 2023)
1-211663464-A-G			Uncertain significance (Sep 27, 2022)
1-211663488-C-T			Uncertain significance (Oct 05, 2022)
1-211663488-C-CTTGA			Uncertain significance (Nov 29, 2021)
1-211663491-G-A			Uncertain significance (Mar 21, 2021)
1-211663493-GC-G		Retinal dystrophy	Likely pathogenic (Oct 01, 2023)
1-211663494-C-G		not specified	Uncertain significance (Nov 18, 2022)
1-211663496-C-T			Uncertain significance (Oct 24, 2022)
1-211663497-G-A			Uncertain significance (Dec 18, 2023)
1-211663507-A-G		NEK2-related disorder	Benign (Nov 13, 2023)
1-211663510-G-A			Likely benign (Dec 05, 2022)
1-211663537-C-T			Likely benign (Oct 29, 2022)
1-211663538-T-C			Uncertain significance (Jun 17, 2023)
1-211663541-G-T			Uncertain significance (Aug 23, 2022)
1-211663550-G-A			Uncertain significance (Aug 30, 2023)
1-211663564-A-C			Likely benign (Oct 28, 2022)
1-211663565-G-C			Uncertain significance (Mar 08, 2023)
1-211663580-A-G			Uncertain significance (Aug 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEK2	protein_coding	protein_coding	ENST00000366999	8	12847

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000115	0.988	125653	0	95	125748	0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	188	245	0.767	0.0000135	2904
Missense in Polyphen		55	83.402	0.65946		910
Synonymous	0.206	87	89.5	0.972	0.00000463	839
Loss of Function	2.28	14	26.8	0.523	0.00000188	286

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.000979
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000584	0.000545
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000340	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856}.; FUNCTION: Isoform 2: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S- arrested cells. {ECO:0000269|PubMed:15161910}.
• Disease: DISEASE: Retinitis pigmentosa 67 (RP67) [MIM:615565]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:24043777}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;APC-Cdc20 mediated degradation of Nek2A;APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint;APC/C:Cdc20 mediated degradation of mitotic proteins;Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;FOXM1 transcription factor network;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.205

Intolerance Scores

• loftool: 0.604
• rvis_EVS: -0.31
• rvis_percentile_EVS: 31.93

Haploinsufficiency Scores

• pHI: 0.852
• hipred: Y
• hipred_score: 0.715
• ghis: 0.661

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nek2

Zebrafish Information Network

• Gene name: nek2
• Affected structure: retinal rod cell
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: mitotic sister chromatid segregation;G2/M transition of mitotic cell cycle;mitotic cell cycle;blastocyst development;protein phosphorylation;chromosome segregation;regulation of mitotic nuclear division;regulation of G2/M transition of mitotic cell cycle;positive regulation of telomere maintenance via telomerase;negative regulation of DNA binding;regulation of mitotic centrosome separation;protein autophosphorylation;spindle assembly;centrosome separation;cell division;meiotic cell cycle;positive regulation of telomerase activity;regulation of attachment of spindle microtubules to kinetochore;mitotic spindle assembly;ciliary basal body-plasma membrane docking;negative regulation of centriole-centriole cohesion;positive regulation of telomere capping
• Cellular component: kinetochore;condensed chromosome kinetochore;condensed nuclear chromosome;spindle pole;nucleus;nucleoplasm;nucleolus;centrosome;cytosol;microtubule;midbody;protein-containing complex
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;protein phosphatase binding;metal ion binding