APRT

adenine phosphoribosyltransferase

Basic information

Region (hg38): 16:88809338-88811937

Links

ENSG00000198931 ∙ NCBI:353 ∙ OMIM:102600 ∙ HGNC:626 ∙ Uniprot:P07741 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• adenine phosphoribosyltransferase deficiency (Definitive), mode of inheritance: AR
• adenine phosphoribosyltransferase deficiency (Strong), mode of inheritance: AR
• adenine phosphoribosyltransferase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adenine phosphoribosyltransferase deficiency	AR	Biochemical; Renal	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	Biochemical; Musculoskeletal; Renal	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; 23430916

ClinVar

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

• not provided (64 variants)
• Adenine phosphoribosyltransferase deficiency (51 variants)
• Morquio syndrome (6 variants)
• Inborn genetic diseases (5 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APRT 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				12		12
missense	4	3	25	2	1	35
nonsense	3	2				5
start loss	2					2
frameshift	4	1				5
inframe indel	1	2	1			4
splice donor/acceptor (+/-2bp)		1				1
splice region	1		1	1		3
non coding			5	7	9	21
Total	14	9	31	21	10

Highest pathogenic variant AF is 0.0000591

Variants in APRT

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

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

Position	Type	Phenotype	Significance	ClinVar
16-88809365-TCTG-T			Benign (May 10, 2021)
16-88809429-G-T			Benign (Jul 09, 2018)
16-88809488-T-C		Adenine phosphoribosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
16-88809516-T-C		Morquio syndrome • Adenine phosphoribosyltransferase deficiency	Conflicting classifications of pathogenicity (Jun 14, 2016)
16-88809520-T-C		Morquio syndrome • Adenine phosphoribosyltransferase deficiency	Benign (Jul 09, 2018)
16-88809520-T-G		Adenine phosphoribosyltransferase deficiency	Likely benign (Jan 12, 2018)
16-88809546-G-A		Adenine phosphoribosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
16-88809576-G-A		Adenine phosphoribosyltransferase deficiency	Uncertain significance (Jan 13, 2018)
16-88809615-C-T		Adenine phosphoribosyltransferase deficiency	Uncertain significance (Jun 14, 2016)
16-88809651-A-G		Morquio syndrome • Adenine phosphoribosyltransferase deficiency	Likely benign (Oct 19, 2018)
16-88809695-T-C		Morquio syndrome • Adenine phosphoribosyltransferase deficiency	Benign/Likely benign (Jul 09, 2018)
16-88809698-T-A		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809699-C-G		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809700-A-G		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809709-G-A		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809710-CAGGAG-C		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809712-G-A			Likely benign (Nov 04, 2021)
16-88809715-G-A		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809716-AGAG-A		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809717-G-A		Adenine phosphoribosyltransferase deficiency	Likely pathogenic (Sep 01, 2020)
16-88809717-GAGA-G		Adenine phosphoribosyltransferase deficiency • See cases	Pathogenic/Likely pathogenic (Apr 04, 2024)
16-88809727-G-C		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
16-88809730-CA-C		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809750-C-T		Adenine phosphoribosyltransferase deficiency	Pathogenic (Sep 01, 2020)
16-88809754-TAAG-T			Likely pathogenic (Jun 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APRT	protein_coding	protein_coding	ENST00000378364	5	2606

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.45e-13	0.00218	125581	0	33	125614	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.238	110	103	1.07	0.00000563	1109
Missense in Polyphen		43	39.128	1.099		438
Synonymous	-2.97	73	47.1	1.55	0.00000266	395
Loss of Function	-2.03	15	8.57	1.75	5.06e-7	80

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.000382	0.000381
Finnish	0.0000952	0.0000924
European (Non-Finnish)	0.000145	0.000141
Middle Eastern	0.000382	0.000381
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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.
• Pathway: Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Purine metabolism;Neutrophil degranulation;adenine and adenosine salvage I;Metabolism of nucleotides;Innate Immune System;Immune System;Metabolism;Nucleotide salvage;Purine salvage;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage (Consensus)

Recessive Scores

• pRec: 0.0946

Intolerance Scores

• loftool: 0.271
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.49

Haploinsufficiency Scores

• pHI: 0.612
• hipred: N
• hipred_score: 0.239
• ghis: 0.518

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aprt
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: purine ribonucleoside salvage;adenine salvage;lactation;grooming behavior;cellular response to insulin stimulus;purine-containing compound salvage;neutrophil degranulation;AMP salvage
• Cellular component: extracellular region;nucleoplasm;cytoplasm;cytosol;secretory granule lumen;extracellular exosome
• Molecular function: adenine binding;adenine phosphoribosyltransferase activity;AMP binding