GeneBe

APRT

protein-coding

adenine phosphoribosyltransferase

Gene summary

Adenine phosphoribosyltransferase belongs to the purine/pyrimidine phosphoribosyltransferase family. A conserved feature of this gene is the distribution of CpG dinucleotides. This enzyme catalyzes the formation of AMP and inorganic pyrophosphate from adenine and 5-phosphoribosyl-1-pyrophosphate (PRPP). It also produces adenine as a by-product of the polyamine biosynthesis pathway. A homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine urolithiasis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000485.3

Inheritance

AR

ClinVar variants

P:70U:67B:25

Top phenotype

Adenine phosphoribosyltransferase deficiency

gnomAD constraint

pLI —, LoF o/e 1.75

Max pathogenic AF

—

Genomic locus

chr16:88,809,339-88,811,937

External References & Databases

Ensembl (ENSG00000198931)NCBI Gene (353)OMIM (102600)HGNC:626GenCCUniProt (P07741)AlphaFoldClinVar (APRT)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~2.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

adenine phosphoribosyltransferase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013869

Submitter: Labcorp Genetics (formerly Invitae)

adenine phosphoribosyltransferase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013869

Submitter: Ambry Genetics

adenine phosphoribosyltransferase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013869

Submitter: PanelApp Australia

adenine phosphoribosyltransferase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013869

Submitter: Orphanet

Clinical Genomic Database (CGD)

Adenine phosphoribosyltransferase deficiencyAR

Manifestation: Biochemical; Musculoskeletal; Renal

Intervention: Biochemical; Renal

Rationale: Medical and dietary interventions (eg, purine-restricted diet with adequate hydration and allopurinol or febuxostat, in instances where allopurinol can not be used) may be beneficial in order to decrease the severity of manifestations including nephrolithiasis and renal sequelae, as well as to treat individuals with relatively advanced disease; Renal transplant has been described, and disease-specific considerations (eg, immediate postoperative pharmacotherapy) may impact transplant outcomes

Refs: 5676523; 5763607; 4852180; 1061547; 7766; 865583; 420519; 7311997; 6701033; 3876264; 3680503; 1353080; 806829; 3077470; 3409638; 3343350; 1986109; 1985452; 1353080; 1349689; 1349687; 7915931; 8825602; 9298830; 9521589; 11532677; 14767036; 15025810; 15077874; 15571218; 17126311; 19435978; 20101413; 20150536; 20303634; 20553441; 21635362; 22212387; 22934314; 22988602; 23430916Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APRT variants in ClinVar

7 Conditions Cataloged
Adenine phosphoribosyltransferase deficiencyTotal: 118
not providedTotal: 81
Inborn genetic diseasesTotal: 20
APRT-related disorderTotal: 16
not specifiedTotal: 6
APRT deficiency, Japanese typeTotal: 1
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000485.3. 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
2
clinvar
20
clinvar
 22
missense
17
clinvar
11
clinvar
64
clinvar
4
clinvar
1
clinvar
 97
nonsense
6
clinvar
5
clinvar
 11
start loss
4
clinvar
 4
frameshift
13
clinvar
6
clinvar
 19
splice donor/acceptor (+/-2bp)
4
clinvar
4
clinvar
1
clinvar
 9
Total442667241162

Highest pathogenic variant AF is 0.00018537026

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000485.3RefSeqNP_000476.15MANE Select
ENST00000378364.8EnsemblENSP00000367615.35MANE Select
NM_001030018.2RefSeqNP_001025189.15Standard
ENST00000426324.6EnsemblENSP00000397007.25Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

  • purine ribonucleoside salvage
  • adenine salvage
  • lactation
  • grooming behavior
  • cellular response to insulin stimulus

Molecular Function

  • adenine binding
  • adenine phosphoribosyltransferase activity
  • AMP binding

Cellular Component

  • extracellular region
  • nucleoplasm
  • cytoplasm
  • cytosol
  • secretory granule lumen

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000378364
Coding exons
5
Length
2606
Individuals with no LoFs
125581
Homozygous LoFs
0
Heterozygous LoFs
33
Defined
125614
p
0.000131
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.2381101031.070.000005631109
Missense (PolyPhen)4339.1281.099438
Synonymous-2.977347.11.550.00000266395
Loss of Function-2.03158.571.755.06e-780

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.000170.00017rare
Ashkenazi Jewish00.0absent
East Asian0.000380.00038rare
Finnish0.0000950.000092rare
European (Non-Finnish)0.000150.00014rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.;
Disease
DISEASE: Adenine phosphoribosyltransferase deficiency (APRTD) [MIM:614723]: An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones. {ECO:0000269|PubMed:11243733, ECO:0000269|PubMed:1353080, ECO:0000269|PubMed:15571218, ECO:0000269|PubMed:1746557, ECO:0000269|PubMed:21635362, ECO:0000269|PubMed:3343350, ECO:0000269|PubMed:3680503, ECO:0000269|PubMed:7915931}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.0946

Intolerance Scores

LoFtool
0.271
RVIS EVS
-0.1
RVIS percentile EVS
46.49

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.988

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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