ALPK3

alpha kinase 3, the group of I-set domain containing

Basic information

Region (hg38): 15:84817355-84873479

Links

ENSG00000136383 ∙ NCBI:57538 ∙ OMIM:617608 ∙ HGNC:17574 ∙ Uniprot:Q96L96 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiomyopathy, familial hypertrophic 27 (Moderate), mode of inheritance: Semidominant
• Brugada syndrome 1 (Strong), mode of inheritance: AD
• Brugada syndrome 1 (Strong), mode of inheritance: AR
• cardiomyopathy, familial hypertrophic 27 (Strong), mode of inheritance: AR
• cardiomyopathy, familial hypertrophic 27 (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic 27	AD/AR	Cardiovascular	Individuals may manifest with early-onset, severe cardiomyopathy, and awareness may allow medical and/or surgical management; Heterozygotes may also be at increased risk of cardiomyopathy, and awareness may be beneficial to allow surveillance and potential management	Cardiovascular	26846950; 27106955; 28223422

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALPK3 gene.

• not provided (1438 variants)
• Cardiovascular phenotype (878 variants)
• not specified (86 variants)
• Cardiomyopathy, familial hypertrophic 27 (69 variants)
• Inborn genetic diseases (39 variants)
• Cardiomyopathy (5 variants)
• Hypertrophic cardiomyopathy (4 variants)
• ALPK3-related condition (3 variants)
• Neurodevelopmental disorder (2 variants)
• ALPK3-related disorder (1 variants)
• Left ventricular noncompaction cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALPK3 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			7	407	6	420
missense			932	23	11	966
nonsense	35	18	5			58
start loss			1			1
frameshift	54	27	7			88
inframe indel			16			16
splice donor/acceptor (+/-2bp)		16	3			19
splice region		1	18	18		37
non coding			32	96	28	156
Total	89	61	1003	526	45

Highest pathogenic variant AF is 0.0000394

Variants in ALPK3

This is a list of pathogenic ClinVar variants found in the ALPK3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-84817357-G-C			Uncertain significance (Feb 21, 2021)
15-84817358-G-GAGC			Uncertain significance (Oct 13, 2021)
15-84817364-C-T		Cardiovascular phenotype	Uncertain significance (Mar 03, 2022)
15-84817365-G-A		Cardiovascular phenotype	Likely benign (Feb 18, 2024)
15-84817368-G-A		Cardiovascular phenotype	Likely benign (Jan 31, 2024)
15-84817368-G-T			Likely benign (Oct 18, 2022)
15-84817370-C-G			Uncertain significance (Jun 05, 2023)
15-84817370-C-T		Cardiovascular phenotype	Uncertain significance (Aug 10, 2022)
15-84817370-CG-C			Uncertain significance (Oct 04, 2022)
15-84817374-C-CG			Uncertain significance (Sep 06, 2023)
15-84817375-A-C			Likely benign (Feb 19, 2022)
15-84817376-G-A		Cardiovascular phenotype	Uncertain significance (Jan 19, 2022)
15-84817377-G-C		Cardiovascular phenotype	Uncertain significance (Oct 02, 2023)
15-84817379-G-T		Cardiovascular phenotype	Uncertain significance (Jan 31, 2024)
15-84817381-C-T			Uncertain significance (Apr 06, 2023)
15-84817382-C-T			Uncertain significance (Dec 27, 2022)
15-84817382-CG-C		Cardiovascular phenotype	Uncertain significance (Jan 28, 2024)
15-84817384-G-A		Cardiovascular phenotype	Uncertain significance (Nov 08, 2023)
15-84817387-G-T			Uncertain significance (Sep 10, 2023)
15-84817389-C-G		not specified • Cardiovascular phenotype	Likely benign (Jul 31, 2023)
15-84817390-G-C		Cardiovascular phenotype	Uncertain significance (Dec 01, 2023)
15-84817392-G-T		Cardiovascular phenotype	Likely benign (Nov 17, 2022)
15-84817397-GG-CT			Uncertain significance (Jan 22, 2024)
15-84817405-G-A			Uncertain significance (May 10, 2022)
15-84817408-G-A			Uncertain significance (Jul 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALPK3	protein_coding	protein_coding	ENST00000258888	14	56803

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.42e-25	0.464	125620	0	128	125748	0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.131	1061	1.07e+3	0.989	0.0000637	12084
Missense in Polyphen		349	360.46	0.9682		3997
Synonymous	-0.395	465	454	1.02	0.0000283	4177
Loss of Function	2.15	48	67.0	0.716	0.00000358	757

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000932	0.000929
Ashkenazi Jewish	0.00	0.00
East Asian	0.000549	0.000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000679	0.000668
Middle Eastern	0.000549	0.000544
South Asian	0.000504	0.000490
Other	0.000173	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in cardiomyocyte differentiation. {ECO:0000305|PubMed:26846950, ECO:0000305|PubMed:27106955, ECO:0000305|PubMed:28630369, ECO:0000305|PubMed:30046096}.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 27 (CMH27) [MIM:618052]: A form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH27 is a severe, early-onset form with features of hypertrophic and dilated cardiomyopathy. {ECO:0000269|PubMed:26846950, ECO:0000269|PubMed:27106955, ECO:0000269|PubMed:28630369, ECO:0000269|PubMed:30046096}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.805
• rvis_EVS: 0.23
• rvis_percentile_EVS: 68.55

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.313
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0827

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alpk3
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); muscle phenotype

Gene ontology

• Biological process: protein phosphorylation;heart development;cardiac muscle cell development
• Cellular component: nucleus
• Molecular function: protein serine/threonine kinase activity;ATP binding