NUAK1

NUAK family kinase 1, the group of NUAK family kinases

Basic information

Region (hg38): 12:106063344-106138954

Links

ENSG00000074590 ∙ NCBI:9891 ∙ OMIM:608130 ∙ HGNC:14311 ∙ Uniprot:O60285 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NUAK1 gene.

• Inborn genetic diseases (29 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUAK1 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	2
missense			25	4	1	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	25	4	3

Variants in NUAK1

This is a list of pathogenic ClinVar variants found in the NUAK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-106066867-T-C		not specified	Likely benign (Mar 14, 2023)
12-106066896-C-T		not specified	Uncertain significance (Sep 12, 2023)
12-106066903-G-A		not specified	Uncertain significance (Jul 16, 2021)
12-106066934-G-T		not specified	Uncertain significance (Jan 22, 2024)
12-106066992-C-T		not specified	Uncertain significance (Jul 20, 2022)
12-106067004-C-A		NUAK1-related disorder	Likely benign (Feb 20, 2023)
12-106067007-G-T		not specified	Uncertain significance (Apr 12, 2022)
12-106067014-G-A		not specified	Uncertain significance (Mar 22, 2023)
12-106067036-G-C		NUAK1-related disorder	Uncertain significance (Nov 22, 2023)
12-106067037-T-A		not specified	Uncertain significance (Mar 01, 2024)
12-106067068-C-T		not specified	Uncertain significance (Dec 30, 2023)
12-106067181-A-G		not specified	Likely benign (Sep 12, 2023)
12-106067185-T-C		not specified	Likely benign (Jul 20, 2022)
12-106067216-G-C		not specified	Uncertain significance (Aug 16, 2021)
12-106067254-C-A		not specified	Uncertain significance (Aug 16, 2021)
12-106067291-G-T		not specified	Uncertain significance (Jun 30, 2023)
12-106067295-C-T		not specified	Uncertain significance (Aug 16, 2022)
12-106067299-T-A		not specified	Likely benign (Jun 21, 2021)
12-106067334-C-T		not specified	Uncertain significance (Feb 13, 2024)
12-106067337-C-T			Benign (May 24, 2018)
12-106067407-T-A		not specified	Uncertain significance (Sep 28, 2021)
12-106067435-C-T			Benign (May 18, 2018)
12-106067436-G-T		not specified	Uncertain significance (Aug 01, 2022)
12-106067439-A-T		not specified	Uncertain significance (Jul 09, 2021)
12-106067460-G-A		not specified	Uncertain significance (Nov 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUAK1	protein_coding	protein_coding	ENST00000261402	7	76694

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0987	0.901	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	309	402	0.768	0.0000245	4335
Missense in Polyphen		120	213.74	0.56144		2301
Synonymous	-0.451	164	157	1.05	0.00000890	1324
Loss of Function	3.51	7	26.5	0.264	0.00000156	284

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000914	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser- 392' and is recruited to the CDKN1A/WAF1 promoter to participate to transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171, ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.409
• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.86

Haploinsufficiency Scores

• pHI: 0.373
• hipred: Y
• hipred_score: 0.822
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.979

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nuak1
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; embryo phenotype; pigmentation 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); vision/eye 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)

Gene ontology

• Biological process: protein phosphorylation;cellular response to DNA damage stimulus;cell adhesion;regulation of cell adhesion;regulation of myosin-light-chain-phosphatase activity;intracellular signal transduction;regulation of cell population proliferation;regulation of signal transduction by p53 class mediator;regulation of cellular senescence
• Cellular component: fibrillar center;nucleus;nucleoplasm;cytoplasm;microtubule cytoskeleton
• Molecular function: p53 binding;protein serine/threonine kinase activity;protein binding;ATP binding;metal ion binding