ALPK2

protein-coding

alpha kinase 2, the group of I-set domain containing

Gene summary

Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Involved in several processes, including epicardium morphogenesis; heart development; and negative regulation of Wnt signaling pathway involved in heart development. Acts upstream of or within regulation of gene expression. Located in basolateral plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_052947.4

Inheritance

—

ClinVar variants

U:2042B:1146

Top phenotype

ALPK2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr18:58,481,247-58,629,091

External References & Databases

Ensembl (ENSG00000198796)

Transcript & Mutation Effects

hg38 • Region Span ~147.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALPK2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 3153

ALPK2-related disorderTotal: 45

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052947.4. 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			3 clinvar	1006 clinvar	2 clinvar	1011
missense			2034 clinvar	129 clinvar	9 clinvar	2172
nonsense			5 clinvar			5
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	2042	1135	11	3188

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052947.4	RefSeq	NP_443179.3	12	MANE Select
ENST00000361673.4	Ensembl	ENSP00000354991.3	12	MANE Select
ENST00000857519.1	Ensembl	ENSP00000527578.1	12	Standard
ENST00000857519.2	Ensembl	ENSP00000527578.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
alpk2	Danio rerio	Structure: cardiac muscle cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

alpk2

Danio rerio

Structure: cardiac muscle cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation

Molecular Function

protein serine/threonine kinase activity
ATP binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361673
Coding exons: 12
Length: 147711
Individuals with no LoFs: 125640
Homozygous LoFs: 0
Heterozygous LoFs: 107
Defined: 125747
p: 0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.406	1084	1.12e+3	0.966	0.0000580	14256
Missense (PolyPhen)		248	244.11	1.0159		3254
Synonymous	-0.251	444	437	1.02	0.0000249	4232
Loss of Function	2.84	45	70.8	0.635	0.00000326	989

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.0040	0.0040	notable
East Asian	0.00017	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00079	0.00078	rare
Other	0.00067	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation.;

Recessive Scores

pRec: 0.0748

Intolerance Scores

LoFtool: 0.966
RVIS EVS: 4.93
RVIS percentile EVS: 99.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0375

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High