PRPSAP1

Summary

PRPSAP1 (phosphoribosyl pyrophosphate synthetase associated protein 1, HGNC:9466) is a protein-coding gene on chromosome 17q25.1, encoding Phosphoribosyl pyrophosphate synthase-associated protein 1 (Q14558). Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis.

Enables identical protein binding activity. Predicted to be involved in 5-phosphoribose 1-diphosphate biosynthetic process and purine nucleotide biosynthetic process. Predicted to be active in cytoplasm.

Source: NCBI Gene 5635 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_002766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9466
Approved symbol	PRPSAP1
Name	phosphoribosyl pyrophosphate synthetase associated protein 1
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	PAP39
Ensembl gene	ENSG00000161542
Ensembl biotype	protein_coding
OMIM	601249
Entrez	5635

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000324684, ENST00000423915, ENST00000435555, ENST00000436498, ENST00000442767, ENST00000446526, ENST00000472686, ENST00000488339, ENST00000494662, ENST00000586137, ENST00000588364, ENST00000592474, ENST00000908407, ENST00000908408, ENST00000922958, ENST00000941093

RefSeq mRNA: 3 — MANE Select: NM_002766 NM_001330503, NM_001366236, NM_002766

CCDS: CCDS11743, CCDS82209

Canonical transcript exons

ENST00000446526 — 10 exons

Exon	Start	End
ENSE00001118051	76330043	76330098
ENSE00001118054	76330551	76330666
ENSE00001386300	76353534	76353916
ENSE00002927085	76309478	76311700
ENSE00003474852	76332263	76332435
ENSE00003493716	76344671	76344737
ENSE00003661198	76348529	76348581
ENSE00003668552	76313821	76313891
ENSE00003785760	76312870	76313016
ENSE00003788042	76328717	76328862

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.1749 / max 153.1295, expressed in 1812 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168204	27.4729	1808
168201	3.7436	1625
168202	0.3936	146
168203	0.3202	149
168205	0.2446	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	97.35	gold quality
right lobe of thyroid gland	UBERON:0001119	97.32	gold quality
lower esophagus mucosa	UBERON:0035834	97.29	gold quality
saliva-secreting gland	UBERON:0001044	97.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.14	gold quality
minor salivary gland	UBERON:0001830	97.01	gold quality
left lobe of thyroid gland	UBERON:0001120	96.95	gold quality
left testis	UBERON:0004533	96.80	gold quality
thyroid gland	UBERON:0002046	96.76	gold quality
right testis	UBERON:0004534	96.70	gold quality
right lung	UBERON:0002167	96.07	gold quality
mouth mucosa	UBERON:0003729	95.91	gold quality
ventricular zone	UBERON:0003053	95.78	gold quality
right adrenal gland cortex	UBERON:0035827	95.58	gold quality
testis	UBERON:0000473	95.55	gold quality
tibial nerve	UBERON:0001323	95.52	gold quality
right lobe of liver	UBERON:0001114	95.39	gold quality
ectocervix	UBERON:0012249	95.36	gold quality
right uterine tube	UBERON:0001302	95.29	gold quality
endocervix	UBERON:0000458	95.23	gold quality
esophagus mucosa	UBERON:0002469	95.19	gold quality
gall bladder	UBERON:0002110	95.09	gold quality
rectum	UBERON:0001052	95.01	gold quality
stromal cell of endometrium	CL:0002255	94.98	gold quality
right adrenal gland	UBERON:0001233	94.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.91	gold quality
body of pancreas	UBERON:0001150	94.77	gold quality
metanephros cortex	UBERON:0010533	94.77	gold quality
cortical plate	UBERON:0005343	94.54	gold quality
mucosa of transverse colon	UBERON:0004991	94.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, GLI1

miRNA regulators (miRDB)

27 targeting PRPSAP1, 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-499A-5P	99.98	70.79	1323
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-626	98.89	66.21	762
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-4764-3P	96.81	67.94	580

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpsap1	ENSDARG00000099222
mus_musculus	Prpsap1	ENSMUSG00000015869
rattus_norvegicus	Prpsap1	ENSRNOG00000010083
drosophila_melanogaster	CG2246	FBGN0039790
caenorhabditis_elegans		WBGENE00012258

Paralogs (4): PRPS2 (ENSG00000101911), PRPSAP2 (ENSG00000141127), PRPS1 (ENSG00000147224), PRPS1L1 (ENSG00000229937)

Protein

Protein identifiers

Phosphoribosyl pyrophosphate synthase-associated protein 1 — Q14558 (reviewed: Q14558)

Alternative names: 39 kDa phosphoribosypyrophosphate synthase-associated protein

All UniProt accessions (6): B4DP31, C9J168, C9JKT9, C9JNQ3, C9JUN4, Q14558

UniProt curated annotations — full annotation on UniProt →

Function. Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis.

Subunit / interactions. Binds to PRPS1 and PRPS2.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the ribose-phosphate pyrophosphokinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14558-1	1	yes
Q14558-2	2

RefSeq proteins (3): NP_001317432, NP_001353165, NP_002757* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005946	Rib-P_diPkinase	Family
IPR029057	PRTase-like	Homologous_superfamily
IPR029099	Pribosyltran_N	Domain

Pfam: PF13793, PF14572

UniProt features (41 total): strand 16, helix 13, modified residue 4, turn 3, sequence conflict 2, chain 1, initiator methionine 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2C4K	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14558-F1	89.01	0.76

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 (4): 1, 177, 215, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): MODULE_52, GRUETZMANN_PANCREATIC_CANCER_DN, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_RAD21, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, MODULE_206, DELYS_THYROID_CANCER_DN

GO Biological Process (4): 5-phosphoribose 1-diphosphate biosynthetic process (GO:0006015), nucleobase-containing compound metabolic process (GO:0006139), purine nucleotide biosynthetic process (GO:0006164), nucleotide biosynthetic process (GO:0009165)

GO Molecular Function (5): magnesium ion binding (GO:0000287), enzyme inhibitor activity (GO:0004857), enzyme regulator activity (GO:0030234), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
ribose phosphate biosynthetic process	1
5-phosphoribose 1-diphosphate metabolic process	1
primary metabolic process	1
purine nucleotide metabolic process	1
nucleotide biosynthetic process	1
purine-containing compound biosynthetic process	1
nucleotide metabolic process	1
nucleoside phosphate biosynthetic process	1
metal ion binding	1
enzyme regulator activity	1
molecular function inhibitor activity	1
molecular function regulator activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPSAP1	MSMB	P08118	652
PRPSAP1	LRP2BP	Q9P2M1	614
PRPSAP1	IVNS1ABP	Q9Y6Y0	579
PRPSAP1	PCMTD2	Q9NV79	541
PRPSAP1	DPY19L3	Q6ZPD9	540
PRPSAP1	METTL23	Q86XA0	505
PRPSAP1	RNF157	Q96PX1	496
PRPSAP1	PPP1R3G	B7ZBB8	495
PRPSAP1	NLRP13	Q86W25	490
PRPSAP1	CHST10	O43529	485
PRPSAP1	ZC3H8	Q8N5P1	477
PRPSAP1	MTMR1	Q13613	463
PRPSAP1	PRDM13	Q9H4Q3	459
PRPSAP1	PRPS2	P11908	452
PRPSAP1	CMTM4	Q8IZR5	449
PRPSAP1	TAF1	P21675	449

IntAct

119 interactions, top by confidence:

A	B	Type	Score
PRPS1	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.940
PRPSAP1	PRPS1	psi-mi:“MI:0915”(physical association)	0.940
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
PRPSAP1	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.740
PRPSAP2	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.740
HOMER1	TRAF5	psi-mi:“MI:0914”(association)	0.740
PRPSAP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.740
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PRPS2	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.670
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
PRPS1	NMT2	psi-mi:“MI:0914”(association)	0.640
PRS1	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.560
PRPSAP1	PRS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (147): PRPSAP1 (Two-hybrid), PRPSAP1 (Two-hybrid), PRPSAP1 (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), PRPSAP2 (Affinity Capture-MS), PRPSAP1 (Two-hybrid), PLEKHF2 (Two-hybrid), PRPSAP1 (Two-hybrid), PRPSAP1 (Affinity Capture-MS), PRPSAP1 (Co-fractionation), PRPSAP1 (Co-fractionation), PRPSAP1 (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS)

ESM2 similar proteins: A1UQU4, A2VDS0, A6ZME2, B3LLX6, C7GL41, C8ZET8, F4I1A6, O08618, O14081, O14145, O60256, O65583, O74427, P0CF18, P0DC00, P0DC01, P27515, P32895, P41831, P60314, P87171, Q06GM8, Q08DW2, Q14558, Q28DH0, Q54QU9, Q5RBA8, Q5XC85, Q5XH12, Q5ZL26, Q63468, Q6G1B4, Q75JN8, Q7L7V1, Q8DU94, Q8DZK4, Q8E568, Q8P137, Q8R574, Q8VYB2

Diamond homologs: A2VDS0, A6W1C7, O08618, O33924, O60256, O67556, O94413, P09330, P0A1V6, P0A1V7, P0A717, P0A718, P0A719, P11908, P14193, P21108, P32895, P38063, P38620, P38689, P41831, P42816, P44328, P46585, P56184, P57266, P60891, P60892, P65234, P65235, P65236, P65237, P65238, P65239, P65240, P87171, Q08DW2, Q14558, Q1LTH2, Q28DH0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FCERI mediated MAPK activation	6	31.0×	2e-06
Parasite infection	6	31.0×	2e-06
Leishmania phagocytosis	6	31.0×	2e-06
FCGR3A-mediated phagocytosis	11	30.7×	3e-11
RHO GTPases Activate WASPs and WAVEs	6	28.4×	3e-06
RHOV GTPase cycle	6	25.6×	6e-06
Fcgamma receptor (FCGR) dependent phagocytosis	6	24.9×	6e-06
Regulation of actin dynamics for phagocytic cup formation	9	24.7×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	5	40.4×	4e-05
ephrin receptor signaling pathway	5	19.8×	7e-04
positive regulation of actin filament polymerization	5	19.0×	8e-04
integrin-mediated signaling pathway	7	12.9×	2e-04
cell surface receptor protein tyrosine kinase signaling pathway	5	10.0×	7e-03
transforming growth factor beta receptor signaling pathway	5	9.1×	8e-03
MAPK cascade	5	8.8×	9e-03
actin filament organization	6	8.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1844 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76312864:CCTGA:C	donor_loss	1.0000
17:76312865:CTGAC:C	donor_loss	1.0000
17:76312866:TGA:T	donor_loss	1.0000
17:76312867:GACC:G	donor_loss	1.0000
17:76312869:CCTCG:C	donor_loss	1.0000
17:76313012:TCATC:T	acceptor_gain	1.0000
17:76313013:CATC:C	acceptor_gain	1.0000
17:76313013:CATCC:C	acceptor_gain	1.0000
17:76313014:ATC:A	acceptor_gain	1.0000
17:76313015:TC:T	acceptor_gain	1.0000
17:76313015:TCC:T	acceptor_loss	1.0000
17:76313016:CC:C	acceptor_gain	1.0000
17:76313016:CCTGG:C	acceptor_loss	1.0000
17:76313017:C:CC	acceptor_gain	1.0000
17:76313017:CTG:C	acceptor_loss	1.0000
17:76313018:T:G	acceptor_loss	1.0000
17:76313767:A:AC	donor_gain	1.0000
17:76313768:C:CC	donor_gain	1.0000
17:76313887:CATCA:C	acceptor_gain	1.0000
17:76313889:TCA:T	acceptor_gain	1.0000
17:76313890:CA:C	acceptor_gain	1.0000
17:76313890:CAC:C	acceptor_gain	1.0000
17:76313892:C:CC	acceptor_gain	1.0000
17:76328711:T:C	donor_gain	1.0000
17:76328711:TCTTA:T	donor_loss	1.0000
17:76328712:CTTAC:C	donor_loss	1.0000
17:76328713:TTACA:T	donor_loss	1.0000
17:76328714:TAC:T	donor_loss	1.0000
17:76328715:A:AC	donor_gain	1.0000
17:76328716:C:CA	donor_gain	1.0000

AlphaMissense

2516 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000025741 (17:76339611 G>C), RS1000039552 (17:76347996 A>C), RS1000108425 (17:76343255 G>A,C), RS1000140669 (17:76353488 G>C), RS1000141047 (17:76343013 G>A,C), RS1000171299 (17:76340165 G>A), RS1000172370 (17:76353361 C>T), RS1000252842 (17:76349103 GA>G), RS1000266899 (17:76311518 C>G), RS1000272203 (17:76310421 C>T), RS1000293066 (17:76354086 C>A,T), RS1000348129 (17:76338573 T>C,G), RS1000372119 (17:76321464 C>G), RS1000388458 (17:76353930 C>A,G), RS1000435232 (17:76322643 C>A)

Disease associations

OMIM: gene MIM:601249 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001791_20	Urate levels	2.000000e-07
GCST009007_4	High-grade serous ovarian cancer	5.000000e-07
GCST011155_22	Nontraumatic osteonecrosis of the femoral head	8.000000e-06
GCST90002385_320	High light scatter reticulocyte count	2.000000e-14
GCST90002386_194	High light scatter reticulocyte percentage of red cells	6.000000e-12
GCST90002404_178	Red cell distribution width	3.000000e-12
GCST90002405_390	Reticulocyte count	8.000000e-45

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:1001516	ovarian serous carcinoma
EFO:1001930	idiopathic osteonecrosis of the femoral head
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
pentabromodiphenyl ether	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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