NUAK2

NUAK family kinase 2, the group of NUAK family kinases

Basic information

Region (hg38): 1:205302063-205321745

Links

ENSG00000163545 ∙ NCBI:81788 ∙ OMIM:608131 ∙ HGNC:29558 ∙ Uniprot:Q9H093 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• anencephaly 2 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anencephaly 2	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	Craniofacial; Neurologic; Ophthalmologic	32845958

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NUAK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUAK2 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				2	1	3
missense			50	3		53
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	50	5	1

Variants in NUAK2

This is a list of pathogenic ClinVar variants found in the NUAK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-205303469-A-C		not specified	Uncertain significance (Feb 21, 2024)
1-205303484-C-T		not specified	Uncertain significance (Jan 18, 2025)
1-205303493-G-A		not specified	Uncertain significance (Dec 10, 2024)
1-205303537-C-G		not specified	Uncertain significance (Apr 09, 2024)
1-205303550-C-T		not specified	Uncertain significance (Nov 15, 2024)
1-205303551-G-C		not specified	Uncertain significance (Sep 28, 2022)
1-205303604-G-A		not specified	Likely benign (Dec 14, 2021)
1-205303610-T-C		not specified	Uncertain significance (Feb 28, 2024)
1-205303632-G-A		not specified	Uncertain significance (Jan 27, 2025)
1-205303664-T-A		not specified	Uncertain significance (Feb 13, 2024)
1-205303685-G-A		not specified	Uncertain significance (Jul 09, 2024)
1-205303724-C-T		not specified	Uncertain significance (Aug 08, 2023)
1-205303733-C-T		not specified	Likely benign (Dec 22, 2024)
1-205303746-G-A		not specified	Uncertain significance (Dec 31, 2024)
1-205303754-G-T		not specified	Uncertain significance (Dec 14, 2024)
1-205303791-C-T		not specified	Likely benign (Oct 03, 2022)
1-205303802-G-A		not specified	Uncertain significance (May 04, 2023)
1-205303821-C-T		not specified	Uncertain significance (Feb 10, 2022)
1-205303871-G-A		not specified	Uncertain significance (Aug 14, 2024)
1-205303872-G-A		not specified	Uncertain significance (Jan 21, 2025)
1-205303912-G-A			Benign (Mar 01, 2024)
1-205303913-C-A		not specified	Uncertain significance (Jan 23, 2025)
1-205303922-A-G		not specified	Uncertain significance (May 20, 2024)
1-205303948-G-A			Likely benign (Dec 01, 2022)
1-205303974-G-A		not specified	Uncertain significance (Jul 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUAK2	protein_coding	protein_coding	ENST00000367157	7	19697

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000499	0.993	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	324	390	0.831	0.0000235	4060
Missense in Polyphen		119	160.93	0.73943		1824
Synonymous	0.368	155	161	0.963	0.00000926	1310
Loss of Function	2.40	11	23.6	0.466	0.00000133	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000348	0.000335
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000196	0.000193
Middle Eastern	0.000272	0.000272
South Asian	0.000261	0.000163
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95- activated tumor cells. Able to phosphorylate 'Ser-464' of LATS1. {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127}.

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.508
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.02

Haploinsufficiency Scores

• pHI: 0.114
• hipred: N
• hipred_score: 0.351
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nuak2
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland 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); digestive/alimentary phenotype; vision/eye 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); neoplasm; pigmentation phenotype; embryo phenotype

Gene ontology

• Biological process: protein phosphorylation;apoptotic process;actin cytoskeleton organization;intracellular signal transduction;cellular response to glucose starvation;negative regulation of apoptotic process
• Cellular component: nucleus;cytoplasm
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;protein binding;ATP binding