ALPK3

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

Basic information

Region (hg38): 15:84817356-84873479

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
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
cardiomyopathy, familial hypertrophic 27 (Strong), mode of inheritance: AD
cardiomyopathy, familial hypertrophic 27 (Strong), 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 (2032 variants)
Cardiovascular_phenotype (1369 variants)
not_specified (135 variants)
Cardiomyopathy,_familial_hypertrophic_27 (132 variants)
ALPK3-related_disorder (71 variants)
Hypertrophic_cardiomyopathy (13 variants)
Cardiomyopathy (8 variants)
Neurodevelopmental_disorder (2 variants)
Abnormality_of_the_cardiovascular_system (1 variants)
Primary_dilated_cardiomyopathy (1 variants)
pediatric-onset_cardiomyopathy (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. These statistics are base on transcript: NM_000020778.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		13 clinvar	605 clinvar	3 clinvar	622
missense	3 clinvar	3 clinvar	1328 clinvar	151 clinvar	7 clinvar	1492
nonsense	59 clinvar	26 clinvar	8 clinvar	1 clinvar		94
start loss			2			2
frameshift	83 clinvar	43 clinvar	11 clinvar			137
splice donor/acceptor (+/-2bp)		32 clinvar	4 clinvar			36
Total	146	104	1366	757	10

Highest pathogenic variant AF is 0.00013235759

Loading clinvar variants...

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