APRT

Summary

APRT (adenine phosphoribosyltransferase, HGNC:626) is a protein-coding gene on chromosome 16q24.3, encoding Adenine phosphoribosyltransferase (P07741). Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.

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.

Source: NCBI Gene 353 — RefSeq curated summary.

At a glance

• Gene–disease (curated): adenine phosphoribosyltransferase deficiency (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 218 total — 57 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:626
Approved symbol	APRT
Name	adenine phosphoribosyltransferase
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198931
Ensembl biotype	protein_coding
OMIM	102600
Entrez	353

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000378364, ENST00000426324, ENST00000562464, ENST00000563655, ENST00000564858, ENST00000567057, ENST00000567391, ENST00000567713, ENST00000568319, ENST00000568575, ENST00000569616, ENST00000880214, ENST00000880215, ENST00000912467, ENST00000912468, ENST00000912469, ENST00000912470, ENST00000912471, ENST00000912472, ENST00000912473

RefSeq mRNA: 2 — MANE Select: NM_000485 NM_000485, NM_001030018

CCDS: CCDS32511, CCDS45546

Canonical transcript exons

ENST00000378364 — 5 exons

Exon	Start	End
ENSE00001503917	88810423	88810556
ENSE00001503918	88811550	88811656
ENSE00002584924	88809339	88809840
ENSE00002599163	88811820	88811928
ENSE00003473485	88810070	88810148

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.1645 / max 545.9404, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158581	116.4593	1823
158580	0.7052	337

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	98.73	gold quality
skin of leg	UBERON:0001511	98.72	gold quality
lower esophagus mucosa	UBERON:0035834	98.63	gold quality
granulocyte	CL:0000094	98.59	gold quality
mucosa of transverse colon	UBERON:0004991	98.31	gold quality
body of pancreas	UBERON:0001150	98.26	gold quality
right adrenal gland	UBERON:0001233	98.25	gold quality
esophagus mucosa	UBERON:0002469	98.23	gold quality
right adrenal gland cortex	UBERON:0035827	98.11	gold quality
left adrenal gland cortex	UBERON:0035825	98.10	gold quality
left adrenal gland	UBERON:0001234	98.09	gold quality
body of stomach	UBERON:0001161	97.94	gold quality
adrenal cortex	UBERON:0001235	97.82	gold quality
zone of skin	UBERON:0000014	97.80	gold quality
transverse colon	UBERON:0001157	97.59	gold quality
minor salivary gland	UBERON:0001830	97.59	gold quality
right lobe of liver	UBERON:0001114	97.58	gold quality
endometrium epithelium	UBERON:0004811	97.57	gold quality
right lobe of thyroid gland	UBERON:0001119	97.50	gold quality
left lobe of thyroid gland	UBERON:0001120	97.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.29	gold quality
esophagus	UBERON:0001043	97.26	gold quality
left uterine tube	UBERON:0001303	97.26	gold quality
mouth mucosa	UBERON:0003729	97.25	gold quality
adrenal gland	UBERON:0002369	97.24	gold quality
ectocervix	UBERON:0012249	97.21	gold quality
spleen	UBERON:0002106	97.19	gold quality
omental fat pad	UBERON:0010414	97.16	gold quality
peritoneum	UBERON:0002358	97.13	gold quality
metanephros cortex	UBERON:0010533	97.05	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	10.74
E-MTAB-10596	no	954.26
E-HCAD-8	no	50.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF5, CEBPB, CREM, E2F4, E4F1, ESR1, NFKB, NKX2-1, NR1H3, NR5A1, RARA, REST, SP1, SP3

miRNA regulators (miRDB)

8 targeting APRT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-642B-5P	96.37	67.26	745

Literature-anchored findings (GeneRIF, showing 13)

• kinetic, regulatory and thermostability properties of APRT from erythrocytes of HGPRT deficient patients (PMID:14674717)
• determination of structure and examination of role of deficiency in DHA-urolithiasis (PMID:15196008)
• two novel mutations, G133D and V84M, were found in the APRT gene in Japanese patients with APRT deficiency (PMID:15571218)
• APRT assay in a sample of patient hemolysate showed no detectable activity of the enzyme (25.56+/-9.55 U/L red blood cells in control healthy subjects). (PMID:17126311)
• Data indicates that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and phosphoribosyl pyrophosphate. (PMID:18399692)
• The phosphorylation status of membrane-bound nucleoside diphosphate kinase in epithelia and the role of AMP are reported. (PMID:19399589)
• Case study of 2 year old Japanese boy with APRT deficiency. Genetic analysis showed compound heterozygote APRT*J and missense mutation L33P. APRT deficiency should be suspected in patients with radiolucent kidney stones and urinary 2,8-DHA crystals. (PMID:21635362)
• A new mutation, p.Gln147X, in APRT gene, was found in a patient with adenine phosphoribosyltransferase deficiency. (PMID:24986359)
• A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. (PMID:25735432)
• We found large differences between tumour types and individual tumours in their expression of XDH and APRT Variations in locus-specific DNA methylation and gene copy number correlated with the expression levels of XDH and APRT in human tumours respectively (PMID:30104401)
• binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. The forward reaction is mainly a nucleophilic substitution of type 2 (SN2) with a mix of SN1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted SN2-type mechanism would be involved in the reverse reaction. (PMID:31160323)
• Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency. (PMID:33707627)
• Amp(1q) and tetraploidy are commonly acquired chromosomal abnormalities in relapsed multiple myeloma. (PMID:36433728)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	aprt	ENSDARG00000003519
mus_musculus	Aprt	ENSMUSG00000006589
drosophila_melanogaster	Aprt	FBGN0000109
caenorhabditis_elegans	aprt-1	WBGENE00020557

Protein

Protein identifiers

Adenine phosphoribosyltransferase — P07741 (reviewed: P07741)

All UniProt accessions (5): P07741, H3BQB1, H3BQF1, H3BQZ9, H3BSW3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenine: step 1/1.

Similarity. Belongs to the purine/pyrimidine phosphoribosyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07741-1	1	yes
P07741-2	2

RefSeq proteins (2): NP_000476, NP_001025189 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR005764	Ade_phspho_trans	Family
IPR029057	PRTase-like	Homologous_superfamily
IPR050054	UPRTase/APRTase	Family

Pfam: PF00156

Catalyzed reactions (Rhea), 1 shown:

• AMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + adenine (RHEA:16609)

UniProt features (40 total): sequence variant 10, strand 10, helix 9, modified residue 8, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
6FCH	X-RAY DIFFRACTION	1.45
6FCL	X-RAY DIFFRACTION	1.5
6FD4	X-RAY DIFFRACTION	1.5
6HGR	X-RAY DIFFRACTION	1.52
6FD5	X-RAY DIFFRACTION	1.55
6HGS	X-RAY DIFFRACTION	1.55
6HGP	X-RAY DIFFRACTION	1.7
4X45	X-RAY DIFFRACTION	1.75
1ZN8	X-RAY DIFFRACTION	1.76
6FD6	X-RAY DIFFRACTION	1.8
1ZN7	X-RAY DIFFRACTION	1.83
6HGQ	X-RAY DIFFRACTION	1.9
6FCI	X-RAY DIFFRACTION	1.94
1ZN9	X-RAY DIFFRACTION	2.05
4X44	X-RAY DIFFRACTION	2.05
1ORE	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07741-F1	96.91	0.96

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 2, 4, 15, 30, 60, 66, 114, 135

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-74217	Purine salvage
R-HSA-9734195	Defective APRT disrupts adenine salvage
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-5668914	Diseases of metabolism
R-HSA-8956321	Nucleotide salvage
R-HSA-9734207	Nucleotide salvage defects
R-HSA-9735804	Diseases of nucleotide metabolism

MSigDB gene sets: 305 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, HONMA_DOCETAXEL_RESISTANCE, REACTOME_INNATE_IMMUNE_SYSTEM, CHIBA_RESPONSE_TO_TSA_UP, GOBP_BEHAVIOR, XU_GH1_AUTOCRINE_TARGETS_UP, MODULE_56, GOCC_SECRETORY_GRANULE, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, DAZARD_UV_RESPONSE_CLUSTER_G4, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (7): purine ribonucleoside salvage (GO:0006166), adenine salvage (GO:0006168), grooming behavior (GO:0007625), GMP salvage (GO:0032263), IMP salvage (GO:0032264), AMP salvage (GO:0044209), adenine metabolic process (GO:0046083)

GO Molecular Function (7): adenine binding (GO:0002055), adenine phosphoribosyltransferase activity (GO:0003999), AMP binding (GO:0016208), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), heterocyclic compound binding (GO:1901363)

GO Cellular Component (6): extracellular region (GO:0005576), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Innate Immune System	1
Nucleotide salvage	1
Nucleotide salvage defects	1
Metabolism	1
Immune System	1
Disease	1
Metabolism of nucleotides	1
Diseases of nucleotide metabolism	1
Diseases of metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
purine ribonucleotide salvage	3
purine-containing compound salvage	1
nucleoside salvage	1
purine ribonucleoside biosynthetic process	1
purine nucleobase salvage	1
adenine biosynthetic process	1
behavior	1
GMP biosynthetic process	1
IMP biosynthetic process	1
AMP biosynthetic process	1
purine nucleobase metabolic process	1
purine nucleobase binding	1
purine phosphoribosyltransferase activity	1
adenyl ribonucleotide binding	1
anion binding	1
cation binding	1
binding	1
catalytic activity	1
transferase activity	1
small molecule binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

3294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APRT	HPRT1	P00492	933
APRT	ADK	P55263	925
APRT	GALNS	P34059	857
APRT	PNP	P00491	809
APRT	ADSL	P30566	775
APRT	TAT	P17735	742
APRT	GMPS	P49915	718
APRT	GDA	Q9Y2T3	717
APRT	PPAT	Q06203	717
APRT	ADA	P00813	715
APRT	AMPD3	Q01432	706
APRT	AMPD2	Q01433	699
APRT	AMPD1	P23109	686
APRT	UMPS	P11172	680
APRT	ADSS2	P30520	675

IntAct

56 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
APRT	TTC19	psi-mi:“MI:0915”(physical association)	0.560
APRT	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
APRT	UNC45B	psi-mi:“MI:0915”(physical association)	0.400
APRT	KLHL24	psi-mi:“MI:0915”(physical association)	0.400
MLH1	APRT	psi-mi:“MI:0915”(physical association)	0.370
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
DLD	EIF3D	psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MAPK15	TIMM8A	psi-mi:“MI:0914”(association)	0.350
	PSMD3	psi-mi:“MI:0914”(association)	0.350
NEK10		psi-mi:“MI:0914”(association)	0.350
ANKZF1	PSMC3	psi-mi:“MI:0914”(association)	0.350
PSMB10	DDX46	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
POLD3	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
MFSD4A	TIMM23	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): APRT (Affinity Capture-MS), APRT (Affinity Capture-MS), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), APRT (Co-fractionation), RAB7A (Co-fractionation), SNX12 (Co-fractionation)

ESM2 similar proteins: A0KAK7, A1KV71, A4JHX7, A4TPB0, A5GSL0, A7H8F4, A8AJX4, A9AF06, A9M1N3, A9R0Q1, B1JYN1, B1YN34, B2JCQ7, B2SXI3, B2VHU9, B4T9H6, B5R607, C4L8U7, P07741, P08030, P12426, P36972, P47952, P47956, P47957, P47958, P54363, Q0BBS3, Q145V4, Q1BTI4, Q1C4P3, Q1CL33, Q2INZ6, Q2JI33, Q2JT47, Q2NV62, Q2RWT4, Q39CV8, Q3A4N0, Q3JEP4

Diamond homologs: A0JV33, A0LUK1, A0PPE4, A0Q8C6, A0QIA9, A0QWJ5, A1A1K5, A1KLT2, A1SJB1, A1T894, A1UFB6, A3PYX7, A4FBB2, A4IW38, A4QEM8, A4TBR2, A4X5X7, A5CSP7, A5IZD7, A5U5T4, A5URA4, A6Q2W2, A6TQN8, A6WCH4, A7HVC7, A7NEG0, A7NG77, A8KZE2, A8LXX3, A9WCV7, A9WQH7, B0K0N0, B0RGV9, B0RS13, B1MCI5, B1WQD7, B2HN75, B2SEZ5, B2SHR3, B3DRY2

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
APRT	“down-regulates quantity”	adenine	“chemical modification”
APRT	“down-regulates quantity”	“5-phospho-α-D-ribose 1-diphosphate”	“chemical modification”
APRT	“up-regulates quantity”	AMP	“chemical modification”
APRT	“up-regulates quantity”	diphosphate(3-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

218 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	57
Likely pathogenic	23
Uncertain significance	73
Likely benign	30
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1048365	NC_000016.10:g.88770428_88832724del	Pathogenic
1048367	NC_000016.10:g.(88810557_88811549)_(88841972_88842705)del	Pathogenic
1071729	NM_000485.3(APRT):c.310G>T (p.Glu104Ter)	Pathogenic
1452119	NM_000485.3(APRT):c.270del (p.Lys91fs)	Pathogenic
1458416	NM_000485.3(APRT):c.279_283del (p.Gly94fs)	Pathogenic
18295	NM_000485.3(APRT):c.321+2dup	Pathogenic
18296	NM_000485.3(APRT):c.407T>C (p.Met136Thr)	Pathogenic
18297	NM_000485.3(APRT):c.194A>T (p.Asp65Val)	Pathogenic
18298	NM_000485.3(APRT):c.294G>A (p.Trp98Ter)	Pathogenic
18299	NM_000485.3(APRT):c.258_261dup (p.Lys88fs)	Pathogenic
18300	NM_000485.3(APRT):c.329T>C (p.Leu110Pro)	Pathogenic
18302	NM_000485.3(APRT):c.542G>C (p.Ter181Ser)	Pathogenic
2445490	NC_000016.9:g.(?88870240)(88878307_?)del	Pathogenic
2796942	NM_000485.3(APRT):c.388_397del (p.Leu130fs)	Pathogenic
3021749	NM_000485.3(APRT):c.108del (p.Ala37fs)	Pathogenic
3243321	NC_000016.9:g.(?88851289)(88909257_?)del	Pathogenic
3359185	NM_000485.3(APRT):c.482C>A (p.Ser161Ter)	Pathogenic
3656040	NM_000485.3(APRT):c.452_453dup (p.Glu152fs)	Pathogenic
3697422	NM_000485.3(APRT):c.270dup (p.Lys91fs)	Pathogenic
4074265	NM_000485.3(APRT):c.3G>C (p.Met1Ile)	Pathogenic
41012	NM_000485.3(APRT):c.448G>T (p.Val150Phe)	Pathogenic
4694130	NM_000485.3(APRT):c.254del (p.Leu85fs)	Pathogenic
4698132	NM_000485.3(APRT):c.80+2T>C	Pathogenic
988021	NM_000485.3(APRT):c.522_524del (p.Ser175del)	Pathogenic
988022	NM_000485.3(APRT):c.526C>T (p.Leu176Phe)	Pathogenic
988023	NM_000485.3(APRT):c.526_530del (p.Leu176fs)	Pathogenic
988024	NM_000485.3(APRT):c.532C>T (p.Gln178Ter)	Pathogenic
988026	NM_000485.3(APRT):c.543A>T (p.Ter181Cys)	Pathogenic
988027	NM_000485.2:c.-1_*1del	Pathogenic
988028	NM_000485.3(APRT):c.1A>G (p.Met1Val)	Pathogenic

SpliceAI

881 predictions. Top by Δscore:

Variant	Effect	Δscore
16:88810417:TCTTA:T	donor_loss	1.0000
16:88810418:CTTA:C	donor_loss	1.0000
16:88810419:TTACC:T	donor_loss	1.0000
16:88810420:TA:T	donor_loss	1.0000
16:88810421:A:AG	donor_loss	1.0000
16:88810982:T:TA	donor_gain	1.0000
16:88810065:CTTA:C	donor_loss	0.9900
16:88810066:TTA:T	donor_loss	0.9900
16:88810067:TACCA:T	donor_loss	0.9900
16:88810068:ACC:A	donor_loss	0.9900
16:88810069:CCA:C	donor_gain	0.9900
16:88810146:AGCC:A	acceptor_loss	0.9900
16:88810149:C:CC	acceptor_gain	0.9900
16:88810149:CT:C	acceptor_loss	0.9900
16:88810150:T:G	acceptor_loss	0.9900
16:88810184:C:CT	acceptor_gain	0.9900
16:88810184:C:T	acceptor_gain	0.9900
16:88810421:ACCTT:A	donor_gain	0.9900
16:88810422:CCTTC:C	donor_gain	0.9900
16:88810425:T:A	donor_gain	0.9900
16:88810555:GCCTG:G	acceptor_loss	0.9900
16:88810557:C:CC	acceptor_gain	0.9900
16:88810557:CT:C	acceptor_loss	0.9900
16:88810558:T:A	acceptor_loss	0.9900
16:88810063:CCCTT:C	donor_loss	0.9800
16:88810145:CAGC:C	acceptor_gain	0.9800
16:88810434:C:CA	donor_gain	0.9800
16:88810552:TAGGC:T	acceptor_gain	0.9800
16:88811539:TGGG:T	donor_gain	0.9800
16:88811547:CGC:C	donor_loss	0.9800

AlphaMissense

1127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:88811822:G:C	F26L	0.996
16:88811822:G:T	F26L	0.996
16:88811824:A:G	F26L	0.996
16:88811843:G:C	F19L	0.996
16:88811843:G:T	F19L	0.996
16:88811845:A:G	F19L	0.996
16:88810087:T:A	D128V	0.995
16:88810090:T:A	D127V	0.995
16:88810086:A:C	D128E	0.993
16:88810086:A:T	D128E	0.993
16:88810087:T:G	D128A	0.993
16:88810537:G:C	F69L	0.993
16:88810537:G:T	F69L	0.993
16:88810539:A:G	F69L	0.993
16:88810087:T:C	D128G	0.992
16:88810099:A:T	V124D	0.992
16:88810480:C:A	K88N	0.992
16:88810480:C:G	K88N	0.992
16:88810096:A:T	V125D	0.991
16:88809776:G:C	S155R	0.990
16:88809776:G:T	S155R	0.990
16:88809778:T:G	S155R	0.990
16:88810088:C:G	D128H	0.989
16:88810538:A:G	F69S	0.988
16:88811555:A:T	I61N	0.988
16:88811655:C:G	D28H	0.988
16:88810090:T:G	D127A	0.987
16:88810091:C:G	D127H	0.987
16:88810484:C:G	R87P	0.987
16:88810431:A:G	Y105H	0.986

dbSNP variants (sampled 300 via entrez): RS1000569890 (16:88812316 G>C,T), RS1000734940 (16:88811933 G>A,C,T), RS1001552853 (16:88811925 G>A,C,T), RS1001690023 (16:88811738 GC>G), RS1001891226 (16:88812580 T>C,G), RS1001934534 (16:88812115 G>C), RS1002612482 (16:88813570 A>G), RS1002682485 (16:88813786 G>C), RS1002743528 (16:88810245 C>A,T), RS1003586349 (16:88809708 T>C,G), RS1003685958 (16:88812960 C>G,T), RS1004119379 (16:88809208 T>G), RS1004583219 (16:88813473 G>A,C,T), RS1004971357 (16:88809594 A>C,T), RS1005047521 (16:88809923 G>T)

Disease associations

OMIM: gene MIM:102600 | disease phenotypes: MIM:253000, MIM:614723

GenCC curated gene-disease

Disease	Classification	Inheritance
adenine phosphoribosyltransferase deficiency	Definitive	Autosomal recessive

Mondo (2): mucopolysaccharidosis type 4A (MONDO:0009659), adenine phosphoribosyltransferase deficiency (MONDO:0013869)

Orphanet (3): Mucopolysaccharidosis type 4A (Orphanet:309297), Mucopolysaccharidosis type 4 (Orphanet:582), Adenine phosphoribosyltransferase deficiency (Orphanet:976)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000016	Urinary retention
HP:0000019	Urinary hesitancy
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000787	Nephrolithiasis
HP:0000790	Hematuria
HP:0000791	Uric acid nephrolithiasis
HP:0000822	Hypertension
HP:0001919	Acute kidney injury
HP:0001942	Metabolic acidosis
HP:0002027	Abdominal pain
HP:0003259	Elevated circulating creatinine concentration
HP:0003621	Juvenile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0005110	Atrial fibrillation
HP:0011463	Childhood onset
HP:0011848	Abdominal colic
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0012587	Macroscopic hematuria
HP:0012622	Chronic kidney disease
HP:0030157	Flank pain
HP:0034279	2,8-dihydroxyadenine crystalluria
HP:0034368	Urolithiasis
HP:0100518	Dysuria
HP:0100520	Oliguria
HP:6000803	Elevated urinary 2,8-dihydroxyadenine level

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003479_9	Hair color	1.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538228	Adenine phosphoribosyltransferase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105819 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,167 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2105728	CRENOLANIB	3	2,167

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.88	Kd	13.08	nM	CHEMBL5653589
7.88	ED50	13.08	nM	CHEMBL5653589
7.54	Kd	29	nM	CRENOLANIB

PubChem BioAssay actives

2 with measured affinity, of 186 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147877: Binding affinity to human APRT incubated for 45 mins by Kinobead based pull down assay	kd	0.0131	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1424914: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0290	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
beauvericin	decreases expression	1
bufotalin	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
lead acetate	decreases activity	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
ochratoxin A	increases expression	1
2-amino-3-methylimidazo(4,5-f)quinoline	increases response to substance, increases mutagenesis	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Aspirin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991627	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

22 cell lines: 20 transformed cell line, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0R03	GM07290	Transformed cell line	Male
CVCL_0R04	GM07291	Transformed cell line	Female
CVCL_0R06	GM10807	Transformed cell line	Male
CVCL_5606	WR216	Transformed cell line
CVCL_B2RW	Abcam HEK293T APRT KO	Transformed cell line	Female
CVCL_SD05	HAP1 APRT (-) 1	Cancer cell line	Male
CVCL_SD06	HAP1 APRT (-) 2	Cancer cell line	Male
CVCL_W060	WR002	Transformed cell line
CVCL_W061	WR004	Transformed cell line
CVCL_W062	WR005	Transformed cell line

Clinical trials (associated diseases)

26 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02752633	PHASE4	COMPLETED	Effect of Allopurinol and Febuxostat on Urinary 2,8-Dihydroxyadenine Excretion
NCT01275066	PHASE3	COMPLETED	A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
NCT01415427	PHASE3	COMPLETED	Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
NCT01515956	PHASE2	COMPLETED	Study of BMN 110 in Pediatric Patients < 5 Years of Age With Mucopolysaccharidosis IVA (Morquio A Syndrome)
NCT01609062	PHASE2	TERMINATED	Safety and Exercise Study of Two Doses of BMN 110 for Morquio A Syndrome
NCT01697319	PHASE2	TERMINATED	Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation
NCT03632213	PHASE2	UNKNOWN	Evaluation of Losartan on Cardiovascular Disease in Patients With Mucopolysaccharidoses IV A and VI
NCT04532047	PHASE1	RECRUITING	PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
NCT00588562	Not specified	RECRUITING	Rare Kidney Stone Consortium Patient Registry
NCT02026388	Not specified	RECRUITING	Rare Kidney Stone Consortium Biobank
NCT02780297	Not specified	RECRUITING	Prospective Research Rare Kidney Stones (ProRKS)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT00884949	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA
NCT01242111	PHASE1/PHASE2	TERMINATED	A Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
NCT05845749	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of Voxzogo for Growth Deficits in MPS IVA and VI
NCT00787995	Not specified	TERMINATED	A Clinical Assessment Study of Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)
NCT01457456	Not specified	WITHDRAWN	Biomarker for Morquio Disease (BioMorquio)
NCT01733615	Not specified	TERMINATED	Discovering New Biomarkers For Monitoring Disease Progression in Patients With Mucopolysaccharidosis IVA
NCT01858103	Not specified	APPROVED_FOR_MARKETING	BMN 110 US Expanded Access Program
NCT01920828	Not specified	COMPLETED	Gait Analysis in MPS IVA
NCT01961518	Not specified	COMPLETED	Screening an Orthopedic Population for Mildly-affected Individuals With Morquio Syndrome A and Maroteaux-Lamy Syndrome
NCT02153255	Not specified	WITHDRAWN	Dynamic Gait Analysis in Children With Mucopolysaccharidosis Type IVa
NCT02294877	Not specified	COMPLETED	A Multicenter, Multinational, Observational Morquio A Registry Study (MARS)
NCT05284006	Not specified	RECRUITING	Non-invasive Functional Assessment and Pathogenesis of Morquio A
NCT07361536	Not specified	RECRUITING	Cardiac Structure and Function in MPS