NUAK2

protein-coding

NUAK family kinase 2, the group of NUAK family kinases

Gene summary

Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including cellular response to glucose starvation; protein phosphorylation; and regulation of hippo signaling. Located in nuclear speck. Implicated in anencephaly. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_030952.3

Inheritance

ClinVar variants

P:1U:100B:11

Top phenotype

Anencephaly 2

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr1:205,302,063-205,321,745

External References & Databases

Ensembl (ENSG00000163545)

Transcript & Mutation Effects

hg38 • Region Span ~19.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

anencephaly 2LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030338

Submitter: Labcorp Genetics (formerly Invitae)

anencephaly 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030338

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Anencephaly 2AR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 32845958

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NUAK2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 4

Anencephaly 2Total: 2

NUAK2-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030952.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	1 clinvar	5
missense			98 clinvar	6 clinvar		104
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	100	10	1	112

Highest pathogenic variant AF is 7.097796e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030952.3	RefSeq	NP_112214.3	7	MANE Select
ENST00000367157.6	Ensembl	ENSP00000356125.5	7	MANE Select
ENST00001001367.1	Ensembl	ENSP00000671184.1	5	Standard
ENST00001001368.1	Ensembl	ENSP00000671185.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
apoptotic process
actin cytoskeleton organization
intracellular signal transduction
cellular response to glucose starvation

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367157
Coding exons: 7
Length: 19697
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.18	324	390	0.831	0.0000235	4060
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00026	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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