AK2

adenylate kinase 2, the group of Adenylate kinases

Basic information

Region (hg38): 1:33007986-33080996

Links

ENSG00000004455 ∙ NCBI:204 ∙ OMIM:103020 ∙ HGNC:362 ∙ Uniprot:P54819 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• reticular dysgenesis (Definitive), mode of inheritance: AR
• reticular dysgenesis (Definitive), mode of inheritance: AR
• reticular dysgenesis (Supportive), mode of inheritance: AR
• reticular dysgenesis (Definitive), mode of inheritance: AR
• reticular dysgenesis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Reticular dysgenesis	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic	Individuals typically die in early infancy due to severe infections; Early diagnosis allowing HSCT can be effective	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic	13840590; 6132037; 19043416; 19043417

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AK2 gene.

• Reticular_dysgenesis (170 variants)
• not_provided (34 variants)
• Inborn_genetic_diseases (26 variants)
• AK2-related_disorder (15 variants)
• Severe_combined_immunodeficiency_disease (9 variants)
• not_specified (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001625.4. 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				35	5	40
missense	1	5	85	8	2	101
nonsense	4	1				5
start loss	2					2
frameshift	6	5	3			14
splice donor/acceptor (+/-2bp)	1	3	1			5
Total	14	14	89	43	7

Highest pathogenic variant AF is 0.0000439911

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AK2	protein_coding	protein_coding	ENST00000354858	6	73013

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000627	0.730	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0718	133	135	0.983	0.00000755	1548
Missense in Polyphen		38	46.117	0.82399		599
Synonymous	-2.17	69	49.6	1.39	0.00000264	468
Loss of Function	1.02	8	11.8	0.678	7.53e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000217	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000217	0.000217
South Asian	0.0000695	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis. {ECO:0000255|HAMAP- Rule:MF_03168, ECO:0000269|PubMed:19043416}.
• Disease: DISEASE: Reticular dysgenesis (RDYS) [MIM:267500]: A fatal form of severe combined immunodeficiency, characterized by absence of granulocytes, almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immunity, leading to fatal septicemia within days after birth. In bone marrow of individuals with reticular dysgenesis, myeloid differentiation is blocked at the promyelocytic stage, whereas erythro- and megakaryocytic maturation is generally normal. Inheritance is autosomal recessive. {ECO:0000269|PubMed:19043416, ECO:0000269|PubMed:19043417}. 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);Tenofovir/Adefovir Pathway, Pharmacodynamics;Tenofovir/Adefovir Pathway, Pharmacokinetics;Adefovir Dipivoxil Metabolism Pathway;Tenofovir Metabolism Pathway;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: 0.358

Intolerance Scores

• loftool: 0.555
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

• pHI: 0.497
• hipred: N
• hipred_score: 0.393
• ghis: 0.610

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ak2

Zebrafish Information Network

• Gene name: ak2
• Affected structure: granulocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: ADP biosynthetic process;nucleobase-containing small molecule interconversion;phosphorylation;AMP metabolic process;ATP metabolic process;nucleoside monophosphate phosphorylation
• Cellular component: mitochondrial intermembrane space;extracellular exosome;sperm mitochondrial sheath
• Molecular function: adenylate kinase activity;ATP binding