AK2

adenylate kinase 2, the group of Adenylate kinases

Basic information

Region (hg38): 1:33007985-33080996

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 (Strong), mode of inheritance: AR
reticular dysgenesis (Definitive), 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 (139 variants)
not provided (35 variants)
Inborn genetic diseases (8 variants)
not specified (7 variants)
Severe combined immunodeficiency disease (6 variants)
AK2-related condition (2 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.

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			2 clinvar	21 clinvar	5 clinvar	28
missense	1 clinvar	4 clinvar	67 clinvar	5 clinvar	2 clinvar	79
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift	3 clinvar	4 clinvar	1 clinvar			8
inframe indel			2 clinvar			2
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
splice region ? Intron variants in splice region, excluding donor/acceptor (+/-2bp)	1		1	7	2	11
non coding ? UTR, intron and other, non coding variants			1 clinvar	20 clinvar	13 clinvar	34
Total	7	10	74	46	20

Highest pathogenic variant AF is 0.0000329

Variants in AK2

This is a list of pathogenic ClinVar variants found in the AK2 region.

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

Position	Phenotype	Significance	ClinVar
1-33008227-AGCACCTTTGAGGGGTAGGGATCATTCCTATTCTACTGATGAGGTGAGATAACTTGTCCAAGGTCGCATGGTGAAGTCGCTGTTGAAATCTGTCTTCTGACTCGTTGCTCTGTCTTCATCTGAGGAAAGACTTGTGAGGCTTCTGAGGAGGCTGCTCTCCATCCTGCTGTGTTCTGTCAGTGACACTTTGTGCACACAGGAGATCCTAAGACACATACCCTAGGCCCTCAGAGCCGGCAGTGACTTCTTCAAAATCAGTTCCGGCAGCGCTGAGTGTCCATGGAAAAGAGCTCTTATTCAGAGCAGCCCTTCCTGTGTGCAGAGCTACGCAAGTAATTAAATCACTTCAGCAACAAGATCAAGGGGACGGATAAGTGTTAGAGACTGTGTTTCAGTCCTGACTGCCTCTTATGCATGACCTCAGGAATGCCACTTCACCTCTCTGAGTCTGGTTTCCTCACCTATAAAAGTGAAGGACAGTTCTGACTCCACAGGGTGCTGTGTGAGGGTTACGTGAAGTCGAGGGTTACATGAAGCCTTTGCATAATACCTGGCACAACGTCAGTCTTCCGGGAGTGGTAGGACTAGTCTGCATTCTTGGTTTGCAGATTAGATGAGGAAACCCAGGCCCAAAGAAGCAAACAAACAATAGCTCACCCAGTCTTCTCTGTTTATTCTTCTCAACTACACCATGCTGCTTTGCAGGTTGGTTTGACAAACATTTCCCCACAATTAGATGCATGATGACCAAGGGAGGAAAGAAAATTTTCACAGGGTATTTAAAAAGCTCAGGGAACAAACAGATCAGTGCAAATCAGTAAGGCTAACACCTGAAAATGACTCTGCACAGGTGAGGAAGTGGAGCAGAAGAGGGAGGGGCTGGTTCAGGGAACAGGATTTAATATGTCAGTGAAGACCCTGCCTCTCTCTGTAACAAGATGCCTAAAGAAGAATAGTGGTGCTTCCAGCCCAGCTCCCTCTTGTTTTGGGAACAACAGTCATTTCTCAGAAACCTCACTTGCAAAGGCAGCCCTTCCAAAAACATGAGAGCTTTAGTTTGGAGAAATTATTTAAGCTCACTTTTGCTGGAGAGGAAATGAATTTAAACTAGGACACACAGAGAAGCAACAAAGAGTGTTAAAGAAGCAACTGAAAAGGTAGTCAAAGATCTGGCTTAAGGATTAGAAGCACTGGCTTTCTAGACTATGGACAAGTGTCCATTCAACAGTTATCCAGCCTGGCAGGAAGCAGATATCTTTCTGTGTATATCTGGATCCAACTAACATTTATCCAATGTCTGTTGCATGCCAGGTACTGAGCAAAAACCTTCTTCCTATAAATTTCATTTAATGCCATTAAGGCCAAGAAGGTGGCATAACCAACTTCCTTTTTCAGCTGAGGAAACAGGAGCACAGTGAATAACTAACTGGCTGGGATTTGTCCTAGGTCCCCTGAACTCCAAGCACAGTGCTATCTCCACTAGACCAAGCTGCCTTGTCTCTGGGCTCAAGAGAAGCCTGCATAGGAGCTGAAGGTCAAGAGGTTGCAGGCTTATCTCATATGCACATACTTGGACCTCCCTACCACACAGCTGCCAGCGACAAGAAAGGGCTTCTTTTCCTTCCAGCCAGGTCCAGAATTCAATGTCATTTTTCTAGCTTAGATTATCTAAAAAAAATGCCACAACAGGGGATACAAATTTTAACATATTTTATTGATTTAGGGGCCAAACAAGGCAGCATTTGGTCAGTTAAGAAAGGCACCTCATTGAAAATAATACATCACAGTGCTGTTGAGTGATCCCAGTCACAGGATTTGAGAATGGAAAGGACAATCTTTGGATGACATAGCTTAGGACACTTGCTCATTTATTTAAAAGAGTCCCTTCACACAGTGCAGATAAAAGAAGGCAAGAGCATAGGATTGTGGCATGTGCTGGGTAGCTGTGAGAGGTTACTCATGAAAGTAGGTAGCCTAGTAAATTAGTGGTAAGTCAGGGGAAGGGAATCAGCCTCCCTTTCCATTTCATTCCCTTCCCCCTCCCCTTGATTCCAGTTTGCTTGATTTGTTGAGCCACCATCCCTATGAATACACCTTACATCTCTTTCAAATGTGGAGATGGTTTTTTGATCTTACAGTGTGTGGAACCGGAGTCAGTAATCAAAGCTCCCTGTTCCAAGCTATAGACAGACAGGACAACAATTTGATTTCCTGTACTCTTGGTCTGGAACCCATGGGGTTCTGAGATAAAAGCTGAGGTCTTAGAGCACTGGCTTTAAAAAATATTTTCACCAGTCCAGAGTAAATGAAAACCCGATTCCTTAGAAATAATATTGTGTCTATTTCTACCCCCACCCTCCAAGCATGGTGTTTTTTAAAAAATTAATTTTTCCCTTACACTTTAAAAACTCTCACCTATGTATAAAAGAAACTGCCACACTACAATAACACTGCTGTTGTTCCAAGTATTCCTCTGAGCCCCTCACCAGCCCTCCCTCACCATCCTCACCCTGACCACCCTTCCCCTCTGCCCAGCACCTAAGAGCAGGGATCACGCCGCGGGGTGATGAGCAGTGTTGCAGTCTCGCCTGGCCTTCTGATACTAGGCTGAAATAGAGAGGAAACAAGAGAGAACAAAATGGGTTTTTAAAAACCAAGTACATATCAGAGGAGGCTGGCATGTAAGCCCCAGCAACCAAATGCATTAAACACTGGACATTTCTGTGACAGGTAAAAGCAGAACCTGCTGAGGCTGAGGAACTCTGGAATTAAATGAAGCAAAAACAGAATCCTAACCATACTGAGAAGGGTATATGCATTCCCTATGAATCTTCCAGTTCTTATGGGCAGCCCAAATATTACTTGTACATGTTGTATGCACACGTGAATCTATGTGGACGGATGACAAATATTTGGGCAAGGATCATGCACATAAAATTAGCAAACATTCAAGAACCTCAACTTTGAGGCCAAGTGCTTACAATTGTCCCTAGTTAAAGGGGAGCTGATTCTAAGATTCATGATGCCACTGTCACCCAGAGAAGGATCCCAGACCAGGCACACATAGCTGACAGTTTTTGTTTCACTCCTCTTCCTTGCCCATTCCCAGAAGTCATGTGCTTCCCAGAAACACACAAAGCCAGACTGAGTTTCCATTAAGAGTGGGTGGAGTTGGTTTAGAGCCAGGAAAACAAGGCAGGACAGAGGCAGCAGACACTCACTTGGACCAGGCAAAGAGGGAAGCAAGGTGGCCAGGTACTCATGCCCAGTTGCCATGTGGACAGCAGATAAGACCTCTGGTAGTCTCACAGATGGCAGGAGAGCTCAGGTCAGGAGGCTGGGCACTTTAGAGTCCACTGAATCGAGTCAGCAGCAGATTATGCTGAGGCTGGCGATATTATTTACTGGATCTGCCACTGACTTTCTAATGGTTTTTCCAGAGGCTGCCGTTTTTGTGGTCCTTCATAGCAGTCTGTTACTTCATCTGTTTGCCACAAATCAAACCAGAGACCAAAAGACAGCAGGGACCTTAGAAAATGCTCAATAGTTGGGAAGCTAAGGTTATGAATAAAAGCTGGTAACTGTCACAGGTGGTCTTATTTCTGGGTGATCTTTTCTTGGGGAAGTCCATGGCTATAGCCATCATAAAATTAGGGGTGAAGGGTTGGATCTAGAAAGGAGAGGGTTTGGGCTTAAAAAGAACATATCTGATTTCAGTTTTATGTCCTGGAGAGAGACTGGGTTTGAATAAATACTGATCAAAATGAATCCAAGAATAGATCACACACTGTTTTGTTCACACTTGGAAACACAGGCAAACATTAAAAATAAAAGCAAATAAACCTACCCTGGTCTCTTTTTGGGGAAGTAGATTTGACTGCTCTCAGATGATCAGCCTGGATGTTCAGAAGACAATCTGAATTCAAAAGGACCTTTCACCTGGTTTAATTCTCTGGCAACAATTCAGTTTTCAAACCCAATTCCCAAATAATTGCTATTTTCAGCATCATGATGCAGATCACAAAAATATTCCAATTTGGCCTGGCTCTTTTTATGACGATATCCTCTCCCAGTAATTTCTGTAACCTGCAAAGTAAGTGCCTTTTTCCTTCCACCTAGGGGGAAAAAATTAATGATCCCTGTTCACACACTGACTCACGTGGGTTTTCATCATGGGTTAGAAAACAAAATGGAATTCTCTGTCCATAATGTGCCATCAGGAACTGTGACCCTGCCTGACTTCACATGATCCTGGACTTCTAATCAGCTGCTGGAAATGGAAGAAATACTATGAGGTTCTGGAATTGCGGTCCCTGGAAGATTACCTGGGTTAGTTCATTTTGGTCAAAAAATAAAATCAAAAGTATGGTTAAAGAAGTAAACAGCTGGGCTGGGTGTAGTGGCTCACGTCTGTGATCCTGGCACTTCAGGAGGCCAAGGTGGGTGGATTGCTTAAGCCTAGGAGTTCAAGACCAGCCTGGGCAACTTGGCAAAATCCTGTCTCTACAAAAAATACAAATATCAGCCAGGTGTTGTGGCATGCACCTGTAGTCCCAGCTGCTCAGGAGGCTGAGGTGGGATAATTGCTTGAGCCCCAGGAGGCAGAGGTTGCCGTGAGCCAAGATCACGCCACTGCACTCCAGCCAGGGTGGCAGAGCGAAACCTTGTCTCAAAACAACAACAAAAAAGAAGTAAACAGCTGGTAAAGCAACCTAGCCTAAAACTTACAAAGTAGCAGAGTGAACACATATGTGCATGCACACACACACACACACAACACACATACACACAGATGAGAGTAGCACACACGCCAAAGATACATCAAGCAAGTGCTTTTTTAATCAATACATCAAATGATATTTTTGCTAGCCTGAGGAAGCTTCTCTTTGCCTGTCCTATCATTCCCACCCATTGCCTCACAGGGATGGAAAGAAATTCCTTCTTGGACCCAACATTAGATAAACATAACCAAGTCTTTACATGTGGCTTTGGAGAAGGCTGCTAGGATGCTTGCGAACACGACATCGGGGGTCTGGGAT-A	Reticular dysgenesis	Pathogenic (Jan 01, 2009)	18250
1-33010544-T-C		Benign (Jun 18, 2021)	1262330
1-33010749-C-T		Likely benign (May 18, 2021)	1326153
1-33010802-G-A		Likely benign (May 10, 2021)	1321825
1-33010834-C-A	not specified	Uncertain significance (Mar 29, 2016)	402355
1-33011126-G-A		Benign (Jul 07, 2018)	1246813
1-33012389-GGTTTTCATCATGGGTTAGAAAACAAAATGGAATTCTCTGTCCATAATGTGCCATCAGGAACTGTGACCCTGCCTGACTTCACATGATCCTGGACTTCTAATCAGCTGCTGGAAATGGAAGAAATACTATGAGGTTCTGGAATTGCGGTCCCTGGAAGATTACCTGGGTTAGTTCATTTTGGTCAAAAAATAAAATCAAAAGTATGGTTAAAGAAGTAAACAGCTGGGCTGGGTGTAGTGGCTCACGTCTGTGATCCTGGCACTTCAGGAGGCCAAGGTGGGTGGATTGCTTAAGCCTAGGAGTTCAAGACCAGCCTGGGCAACTTGGCAAAATCCTGTCTCTACAAAAAATACAAATATCAGCCAGGTGTTGTGGCATGCACCTGTAGTCCCAGCTGCTCAGGAGGCTGAGGTGGGATAATTGCTTGAGCCCCAGGAGGCAGAGGTTGCCGTGAGCCAAGATCACGCCACTGCACTCCAGCCAGGGTGGCAGAGCGAAACCTTGTCTCAAAACAACAACAAAAAAGAAGTAAACAGCTGGTAAAGCAACCTAGCCTAAAACTTACAAAGTAGCAGAGTGAACACATATGTGCATGCACACACACACACACACAACACACATACACACAGATGAGAGTAGCACACACGCCAAAGATACATCAAGCAAGTGCTTTTTTAATCAATACATCAAATGATATTTTTGCTAGCCTGAGGAAGCTTCTCTTTGCCTGTCCTATCATTCCCACCCATTGCCTCACAGGGATGGAAAGAAATTCCTTCTTGGACCCAACATTAGATAAACATAACCAAGTCTTTACATGTGGCTTTGGAGAAGGCTGCTAGGATGCTTGCGAACACGACATCGGGGGTCTGGGAT-G	Reticular dysgenesis	Uncertain significance (Nov 09, 2018)	657641
1-33012984-GCA-G		Benign (Jul 22, 2015)	1232355
1-33013179-C-T	AK2-related disorder	Likely benign (Feb 23, 2021)	3054113
1-33013181-T-C	Reticular dysgenesis	Uncertain significance (Oct 07, 2018)	655501
1-33013186-T-TA	Reticular dysgenesis	Uncertain significance (Apr 02, 2021)	1384263
1-33013191-A-G	Reticular dysgenesis	Uncertain significance (Oct 13, 2023)	1465273
1-33013190-C-CATA	Reticular dysgenesis	Uncertain significance (May 25, 2021)	1397284
1-33013198-AGTCTT-TGAGTTTATGTTTATGTTTATGTGTC	Reticular dysgenesis	Uncertain significance (Sep 01, 2022)	2878272
1-33013201-CTT-C	Reticular dysgenesis	Uncertain significance (Oct 13, 2022)	1034623
1-33013204-T-A	Reticular dysgenesis	Pathogenic (Jan 01, 2009)	18261
1-33013231-G-C	Reticular dysgenesis	Uncertain significance (Jul 19, 2022)	567959
1-33013240-C-T	Reticular dysgenesis • Inborn genetic diseases	Uncertain significance (Sep 01, 2021)	1524282
1-33013241-G-A	Reticular dysgenesis	Likely benign (Feb 07, 2020)	1153957
1-33013244-CA-C		Likely pathogenic (Jul 13, 2017)	593198
1-33013246-C-T	Reticular dysgenesis • AK2-related disorder	Uncertain significance (Nov 04, 2022)	664531
1-33013247-G-A	Reticular dysgenesis	Likely benign (Oct 07, 2021)	1611690
1-33013253-G-A	Reticular dysgenesis	Likely benign (Oct 05, 2022)	1086743
1-33013259-C-T	Reticular dysgenesis	Benign (Dec 11, 2023)	738543
1-33013263-G-T	Reticular dysgenesis	Uncertain significance (May 20, 2021)	644601

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
Phenotype

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