NEK9

NIMA related kinase 9

Basic information

Region (hg38): 14:75079352-75127344

Links

ENSG00000119638 ∙ NCBI:91754 ∙ OMIM:609798 ∙ HGNC:18591 ∙ Uniprot:Q8TD19 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• NEK9-related lethal skeletal dysplasia (Supportive), mode of inheritance: AR
• NEK9-related lethal skeletal dysplasia (Moderate), mode of inheritance: AR
• NEK9-related lethal skeletal dysplasia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis, Perthes disease, and upward gaze palsy; Lethal congenital contracture syndrome 10	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	Musculoskeletal; Neurologic	21271645; 26633546; 26908619

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEK9 gene.

• not provided (57 variants)
• Inborn genetic diseases (38 variants)
• Arthrogryposis, Perthes disease, and upward gaze palsy (7 variants)
• NEK9-related lethal skeletal dysplasia (4 variants)
• Goldberg-Shprintzen megacolon syndrome (2 variants)
• - (2 variants)
• NEK9-related lethal skeletal dysplasia;Arthrogryposis, Perthes disease, and upward gaze palsy (2 variants)
• Congenital omphalocele;Congenital contracture (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEK9 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				5	5	10
missense		4	36	5	6	51
nonsense	3	2				5
start loss						0
frameshift	3	1				4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		4	1			5
splice region			1	1	2	4
non coding			1		23	24
Total	6	11	39	10	34

Highest pathogenic variant AF is 0.000296

Variants in NEK9

This is a list of pathogenic ClinVar variants found in the NEK9 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-75084551-C-T		Arthrogryposis, Perthes disease, and upward gaze palsy • NEK9-related lethal skeletal dysplasia	Benign (Sep 05, 2021)
14-75084618-T-G			Benign (Dec 31, 2019)
14-75084623-C-A		Inborn genetic diseases	Uncertain significance (Apr 21, 2022)
14-75084623-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
14-75084650-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
14-75084678-C-T		Inborn genetic diseases	Uncertain significance (Sep 28, 2021)
14-75084739-A-C			Benign (May 13, 2021)
14-75086952-T-C			Benign (May 13, 2021)
14-75087062-T-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
14-75087126-C-G		Inborn genetic diseases	Uncertain significance (May 08, 2023)
14-75087176-G-T		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
14-75087176-GA-TC			Uncertain significance (Mar 10, 2023)
14-75087218-T-C		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
14-75087220-A-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
14-75087227-G-T		Inborn genetic diseases	Uncertain significance (Mar 28, 2023)
14-75088568-T-C		Inborn genetic diseases	Uncertain significance (Nov 03, 2022)
14-75088602-G-T			Benign (Dec 31, 2019)
14-75088787-C-A			Benign (May 30, 2021)
14-75091266-T-C		NEK9-related disorder	Likely benign (Jan 14, 2020)
14-75091278-G-A		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
14-75091289-C-T		Inborn genetic diseases	Uncertain significance (Aug 14, 2023)
14-75091327-T-C			Likely benign (Dec 31, 2019)
14-75091355-C-T			Benign/Likely benign (Apr 01, 2024)
14-75091436-C-T		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
14-75091437-C-T		Inborn genetic diseases	Likely benign (Dec 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEK9	protein_coding	protein_coding	ENST00000238616	22	45226

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.21e-18	0.941	125588	0	160	125748	0.000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.50	365	527	0.693	0.0000276	6330
Missense in Polyphen		78	186.92	0.41729		2238
Synonymous	0.409	192	199	0.963	0.0000105	1944
Loss of Function	2.40	36	55.3	0.651	0.00000304	638

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000701	0.000697
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.000163	0.000163
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000988	0.000985
Middle Eastern	0.000163	0.000163
South Asian	0.000163	0.000163
Other	0.00131	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2. Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues. Important for G1/S transition and S phase progression. Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively. {ECO:0000269|PubMed:12840024, ECO:0000269|PubMed:14660563, ECO:0000269|PubMed:19941817}.
• Disease: DISEASE: Lethal congenital contracture syndrome 10 (LCCS10) [MIM:617022]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:26908619}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Nevus comedonicus (NC) [MIM:617025]: A rare type of epidermal nevus characterized by closely arranged, dilated, plugged follicular ostia in a honeycomb pattern. The plugged ostia contain lamellated keratinaceous material, and their appearance resembles black dots. NC may be non-pyogenic with an acne-like appearance or associated with the formation of cysts, papules, pustules, and abscesses. Most commonly it affects the face and neck area and, by exception, other anatomical regions, including genital area, palms, and soles. NC lesions might present with various patterns of distribution: unilateral, bilateral, linear, interrupted, segmental, or blaschkoid. {ECO:0000269|PubMed:27153399}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arthrogryposis, Perthes disease, and upward gaze palsy (APUG) [MIM:614262]: An autosomal recessive, syndromic form of arthrogryposis, a disease characterized by persistent joints flexure or contracture. APUG patients manifest an unusual combination of arthrogryposis, upward gaze palsy, and avascular necrosis of the hip (Perthes disease). {ECO:0000269|PubMed:26633546}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nuclear Pore Complex (NPC) Disassembly;Activation of NIMA Kinases NEK9, NEK6, NEK7;Nuclear Envelope Breakdown;Mitotic Prophase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.317

Intolerance Scores

• loftool: 0.453
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.83

Haploinsufficiency Scores

• pHI: 0.445
• hipred: Y
• hipred_score: 0.602
• ghis: 0.587

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nek9
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system 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); immune system phenotype

Gene ontology

• Biological process: protein phosphorylation;mitotic nuclear envelope disassembly;cell division
• Cellular component: nucleus;centrosome;cytosol
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;protein kinase binding;metal ion binding