AK1

adenylate kinase 1, the group of MicroRNA protein coding host genes|Adenylate kinases

Basic information

Region (hg38): 9:127866486-127877675

Links

ENSG00000106992 ∙ NCBI:203 ∙ OMIM:103000 ∙ HGNC:361 ∙ Uniprot:P00568 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemolytic anemia due to adenylate kinase deficiency (Supportive), mode of inheritance: AR
• hemolytic anemia due to adenylate kinase deficiency (Strong), mode of inheritance: AR
• hemolytic anemia due to adenylate kinase deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, congenital, nonspherocytic hemolytic, 3	AR	Hematologic	Individuals present with hemolytic anemia (as well as neurodevelopmental features, at least in some reported individuals), and splenectomy has reported as being effective in treatment of hemolysis	Hematologic; Neurologic	179026; 5546784; 6308059; 2542324; 7947281; 9432020; 17662886

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AK1 gene.

• Hemolytic_anemia_due_to_adenylate_kinase_deficiency (48 variants)
• not_provided (34 variants)
• not_specified (19 variants)
• AK1-related_condition (1 variants)
• Adenylate_kinase_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000476.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1		14	1	16
missense	5	1	37	1	1	45
nonsense		2				2
start loss						0
frameshift	1	1				2
splice donor/acceptor (+/-2bp)		1				1
Total	6	6	37	15	2

Highest pathogenic variant AF is 0.0000157705

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AK1	protein_coding	protein_coding	ENST00000373176	6	11264

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0273	0.926	125556	0	184	125740	0.000732

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.649	96	116	0.830	0.00000767	1224
Missense in Polyphen		42	58.242	0.72112		538
Synonymous	0.189	47	48.7	0.966	0.00000333	386
Loss of Function	1.71	4	9.77	0.410	5.07e-7	127

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00307	0.00298
Ashkenazi Jewish	0.000698	0.000695
East Asian	0.000331	0.000326
Finnish	0.00117	0.00116
European (Non-Finnish)	0.000720	0.000712
Middle Eastern	0.000331	0.000326
South Asian	0.0000670	0.0000653
Other	0.00182	0.00179

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. {ECO:0000255|HAMAP-Rule:MF_03171, ECO:0000269|PubMed:23416111}.
• Disease: DISEASE: Hemolytic anemia due to adenylate kinase deficiency (HAAKD) [MIM:612631]: A disease characterized by hemolytic anemia and undetectable erythrocyte adenylate kinase activity. {ECO:0000269|PubMed:12649162, ECO:0000269|PubMed:2542324, ECO:0000269|PubMed:9432020}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Thiamine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Adefovir Dipivoxil Metabolism Pathway;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Tenofovir Metabolism Pathway;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;adenosine ribonucleotides <i>de novo</i> biosynthesis;Metabolism of nucleotides;Interconversion of nucleotide di- and triphosphates;Purine metabolism;Metabolism;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.643

Intolerance Scores

• loftool: 0.377
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.443
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ak1
• Phenotype: 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); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: nucleoside diphosphate phosphorylation;ADP biosynthetic process;nucleoside triphosphate biosynthetic process;nucleobase-containing small molecule interconversion;AMP metabolic process;ATP metabolic process;nucleoside monophosphate phosphorylation
• Cellular component: cytosol;extracellular exosome
• Molecular function: adenylate kinase activity;nucleoside diphosphate kinase activity;ATP binding