NEK8

NIMA related kinase 8

Basic information

Region (hg38): 17:28725897-28743455

Links

ENSG00000160602 ∙ NCBI:284086 ∙ OMIM:609799 ∙ HGNC:13387 ∙ Uniprot:Q86SG6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephronophthisis 9 (Strong), mode of inheritance: AR
• renal-hepatic-pancreatic dysplasia 2 (Strong), mode of inheritance: AR
• nephronophthisis 2 (Supportive), mode of inheritance: AR
• renal-hepatic-pancreatic dysplasia (Supportive), mode of inheritance: AR
• nephronophthisis 9 (Strong), mode of inheritance: AR
• autosomal dominant polycystic kidney disease (Strong), mode of inheritance: AD
• renal-hepatic-pancreatic dysplasia 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal-hepatic-pancreatic dysplasia 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary; Renal	18199800; 23418306; 26697755; 26862157; 26967905
While individuals were first described with having cystic kidneys, later reports included cysts affecting other organs, such as the liver and pancreas, as well as cardiac disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NEK8 gene.

• Nephronophthisis 9 (6 variants)
• Renal-hepatic-pancreatic dysplasia 2 (2 variants)
• Nephronophthisis 9;Renal-hepatic-pancreatic dysplasia 2 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEK8 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	55	3	63
missense			124	4		128
nonsense	4	2				6
start loss						0
frameshift	4	1	3			8
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		6	2			8
splice region			1	6	1	8
non coding			21	33	10	64
Total	8	10	156	92	13

Highest pathogenic variant AF is 0.0000197

Variants in NEK8

This is a list of pathogenic ClinVar variants found in the NEK8 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-28725911-G-C		not specified	Uncertain significance (Feb 10, 2022)
17-28725973-G-C		not specified	Uncertain significance (Dec 27, 2023)
17-28726019-A-G		not specified	Uncertain significance (May 23, 2023)
17-28726024-G-A		not specified	Uncertain significance (Mar 21, 2022)
17-28726058-C-T		not specified	Uncertain significance (Apr 10, 2023)
17-28726757-T-G		not specified	Uncertain significance (Aug 23, 2021)
17-28726774-C-A		not specified	Uncertain significance (Jul 13, 2021)
17-28728822-G-A		Nephronophthisis 9 • NEK8-related disorder	Likely benign (Jul 14, 2016)
17-28728835-C-G		Nephronophthisis 9 • Renal-hepatic-pancreatic dysplasia 2;Nephronophthisis 9	Uncertain significance (Nov 27, 2023)
17-28728836-G-A		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
17-28728847-A-G			Uncertain significance (Nov 08, 2023)
17-28728850-G-A		Renal-hepatic-pancreatic dysplasia 2	Uncertain significance (Jan 06, 2021)
17-28728854-C-T		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
17-28728857-T-C		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
17-28728858-CG-C		not specified	Uncertain significance (Jun 24, 2014)
17-28728861-G-A		Renal-hepatic-pancreatic dysplasia 2	Pathogenic (Feb 14, 2018)
17-28728877-G-A		Nephronophthisis 9	Likely benign (Feb 19, 2022)
17-28728880-G-T		Nephronophthisis 9	Likely benign (Nov 03, 2023)
17-28729007-C-A			Benign (Nov 12, 2018)
17-28729008-C-T			Benign (Nov 12, 2018)
17-28733973-G-A		Nephronophthisis 9	Conflicting classifications of pathogenicity (Jul 22, 2023)
17-28733992-C-T		Nephronophthisis 9	Conflicting classifications of pathogenicity (May 30, 2023)
17-28733994-T-C		Inborn genetic diseases	Uncertain significance (Aug 10, 2021)
17-28734006-A-T		Inborn genetic diseases	Uncertain significance (May 25, 2022)
17-28734026-A-G		Renal-hepatic-pancreatic dysplasia 2	Uncertain significance (Oct 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEK8	protein_coding	protein_coding	ENST00000268766	15	17559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.46e-9	0.993	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	346	411	0.841	0.0000257	4458
Missense in Polyphen		104	147	0.70748		1582
Synonymous	-0.219	170	166	1.02	0.0000102	1473
Loss of Function	2.50	19	34.9	0.544	0.00000214	351

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000486	0.000485
Ashkenazi Jewish	0.00	0.00
East Asian	0.000815	0.000816
Finnish	0.00	0.00
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.000815	0.000816
South Asian	0.000653	0.000653
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for renal tubular integrity. May regulate local cytoskeletal structure in kidney tubule epithelial cells. May regulate ciliary biogenesis through targeting of proteins to the cilia (By similarity). Plays a role in organogenesis and is involved in the regulation of the Hippo signaling pathway. {ECO:0000250, ECO:0000269|PubMed:23418306}.
• Disease: DISEASE: Renal-hepatic-pancreatic dysplasia 2 (RHPD2) [MIM:615415]: A form of renal-hepatic-pancreatic dysplasia, a disease characterized by cystic malformations of the kidneys, liver, and pancreas. The pathological findings consist of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates. {ECO:0000269|PubMed:23418306}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.355
• rvis_EVS: -1.24
• rvis_percentile_EVS: 5.41

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.554
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• 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: Nek8
• Phenotype: renal/urinary 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: nek8
• Affected structure: pronephric proximal convoluted tubule
• Phenotype tag: abnormal
• Phenotype quality: increased diameter

Gene ontology

• Biological process: protein phosphorylation;determination of left/right symmetry;heart development;animal organ morphogenesis;regulation of hippo signaling;cilium assembly
• Cellular component: cytoplasm;cytoskeleton;cilium;ciliary inversin compartment;ciliary base
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;metal ion binding