GeneBe

AK1

protein-coding

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

Gene summary

This gene encodes an adenylate kinase enzyme involved in energy metabolism and homeostasis of cellular adenine nucleotide ratios in different intracellular compartments. This gene is highly expressed in skeletal muscle, brain and erythrocytes. Certain mutations in this gene resulting in a functionally inadequate enzyme are associated with a rare genetic disorder causing nonspherocytic hemolytic anemia. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene shares readthrough transcripts with the upstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]

MANE transcript

NM_000476.3

Inheritance

AR

ClinVar variants

P:10U:47B:22

Top phenotype

Anemia, congenital, nonspherocytic hemolytic, 3

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr9:127,866,486-127,877,675

External References & Databases

Ensembl (ENSG00000106992)NCBI Gene (203)OMIM (103000)HGNC:361GenCCUniProt (P00568)AlphaFoldClinVar (AK1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hemolytic anemia due to adenylate kinase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012967

Submitter: PanelApp Australia

hemolytic anemia due to adenylate kinase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012967

Submitter: Ambry Genetics

hemolytic anemia due to adenylate kinase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012967

Submitter: Orphanet

hemolytic anemia due to adenylate kinase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012967

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Anemia, congenital, nonspherocytic hemolytic, 3AR

Manifestation: Hematologic; Neurologic

Intervention: Hematologic

Rationale: 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

Refs: 179026; 5546784; 6308059; 2542324; 7947281; 9432020; 17662886Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AK1 variants in ClinVar

5 Conditions Cataloged
Hemolytic anemia due to adenylate kinase deficiencyTotal: 49
not providedTotal: 46
not specifiedTotal: 38
AK1-related conditionTotal: 2
Adenylate kinase deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000476.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
18
clinvar
1
clinvar
 19
missense
5
clinvar
1
clinvar
44
clinvar
3
clinvar
 53
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
 4
Total644721179

Highest pathogenic variant AF is 0.00001577049

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000476.3RefSeqNP_000467.16MANE Select
ENST00000644144.2EnsemblENSP00000494600.16MANE Select
NM_001318121.1RefSeqNP_001305050.16Standard
NM_001318122.2RefSeqNP_001305051.16Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Purine metabolism - Homo sapiens (human)
  • Thiamine metabolism - Homo sapiens (human)
  • Purine Nucleoside Phosphorylase Deficiency
  • Mercaptopurine Action Pathway
  • Azathioprine Action Pathway

Biological Process

  • nucleoside diphosphate phosphorylation
  • ADP biosynthetic process
  • nucleoside triphosphate biosynthetic process
  • nucleobase-containing small molecule interconversion
  • AMP metabolic process

Molecular Function

  • adenylate kinase activity
  • nucleoside diphosphate kinase activity
  • ATP binding

Cellular Component

  • cytosol
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000373176
Coding exons
6
Length
11264
Individuals with no LoFs
125556
Homozygous LoFs
0
Heterozygous LoFs
184
Defined
125740
p
0.000732
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.649961160.8300.000007671224
Missense (PolyPhen)4258.2420.72112538
Synonymous0.1894748.70.9660.00000333386
Loss of Function1.7149.770.4105.07e-7127

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00290.0028notable
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish0.000700.00069rare
East Asian0.000330.00033rare
Finnish0.00120.0012notable
European (Non-Finnish)0.000720.00071rare
South Asian0.0000670.000065rare
Other0.00180.0018notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.643

Intolerance Scores

LoFtool
0.377
RVIS EVS
-0.14
RVIS percentile EVS
43.57

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.960

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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