PRPS1L1

Summary

PRPS1L1 (phosphoribosyl pyrophosphate synthetase 1 like 1, HGNC:9463) is a protein-coding gene on chromosome 7p21.1, encoding Ribose-phosphate pyrophosphokinase 3 (P21108). Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.

This intronless gene is specifically expressed in the testis, and encodes a protein that is highly homologous to the two subunits of phosphoribosylpyrophosphate synthetase encoded by human X-linked genes, PRPS1 and PRPS2. These enzymes convert pyrimidine, purine or pyridine bases to the corresponding ribonucleoside monophosphates. In vitro transcription/translation and site-directed mutagenesis studies indicate that translation of this mRNA initiates exclusively at a non-AUG (ACG) codon.

Source: NCBI Gene 221823 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_175886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9463
Approved symbol	PRPS1L1
Name	phosphoribosyl pyrophosphate synthetase 1 like 1
Location	7p21.1
Locus type	gene with protein product
Status	Approved
Aliases	PRPS3
Ensembl gene	ENSG00000229937
Ensembl biotype	protein_coding
OMIM	611566
Entrez	221823

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000506618

RefSeq mRNA: 1 — MANE Select: NM_175886 NM_175886

CCDS: CCDS47552

Canonical transcript exons

ENST00000506618 — 1 exons

Exon	Start	End
ENSE00002050515	18026770	18027846

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 94.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0682 / max 60.9876, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82925	0.0426	3
82926	0.0149	3
82924	0.0107	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.36	gold quality
male germ cell	CL:0000015	92.26	gold quality
left testis	UBERON:0004533	87.96	gold quality
right testis	UBERON:0004534	87.84	gold quality
testis	UBERON:0000473	85.89	gold quality
adult organism	UBERON:0007023	85.48	gold quality
pancreatic ductal cell	CL:0002079	51.45	silver quality
epithelial cell of pancreas	CL:0000083	49.72	gold quality
tibialis anterior	UBERON:0001385	49.71	silver quality
quadriceps femoris	UBERON:0001377	49.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
deltoid	UBERON:0001476	49.22	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
thymus	UBERON:0002370	48.90	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
vastus lateralis	UBERON:0001379	48.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
layer of synovial tissue	UBERON:0007616	47.54	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Translation initiates from a non-AUG (ACG) start codon. (PMID:2168892)
• Data indicate taht candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1, RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no potentially causal variants were identified. (PMID:21734401)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	prps1a	ENSDARG00000015524
danio_rerio	prps1b	ENSDARG00000037506
mus_musculus	Prps1l1	ENSMUSG00000092305
rattus_norvegicus	Prps1l1	ENSRNOG00000032513
drosophila_melanogaster	Prps	FBGN0036030
caenorhabditis_elegans		WBGENE00020107

Paralogs (4): PRPS2 (ENSG00000101911), PRPSAP2 (ENSG00000141127), PRPS1 (ENSG00000147224), PRPSAP1 (ENSG00000161542)

Protein

Protein identifiers

Ribose-phosphate pyrophosphokinase 3 — P21108 (reviewed: P21108)

Alternative names: Phosphoribosyl pyrophosphate synthase 1-like 1, Phosphoribosyl pyrophosphate synthase III

All UniProt accessions (2): P21108, A0A0B4J207

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.

Subunit / interactions. Homodimer. The active form is probably a hexamer composed of 3 homodimers.

Tissue specificity. Testis.

Activity regulation. Activated by magnesium and inorganic phosphate.

Pathway. Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate from D-ribose 5-phosphate (route I): step 1/1.

Similarity. Belongs to the ribose-phosphate pyrophosphokinase family.

RefSeq proteins (1): NP_787082* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR000842	PRib_PP_synth_CS	Conserved_site
IPR005946	Rib-P_diPkinase	Family
IPR029057	PRTase-like	Homologous_superfamily
IPR029099	Pribosyltran_N	Domain
IPR037515	Rib-P_diPkinase_bac	Family

Pfam: PF13793, PF14572

Catalyzed reactions (Rhea), 1 shown:

• D-ribose 5-phosphate + ATP = 5-phospho-alpha-D-ribose 1-diphosphate + AMP + H(+) (RHEA:15609)

UniProt features (10 total): binding site 6, initiator methionine 1, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21108-F1	94.60	0.91

Functional residue map

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

Ligand- & substrate-binding residues (6): 96–101; 128; 130; 130; 139; 143

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-73843	5-Phosphoribose 1-diphosphate biosynthesis

MSigDB gene sets: 81 (showing top): GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, MORF_RAD51L3, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, MORF_CTSB, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, KEGG_PENTOSE_PHOSPHATE_PATHWAY, GOBP_NUCLEOSIDE_MONOPHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_PURINE_METABOLISM, GOBP_SEX_DIFFERENTIATION, FREAC4_01

GO Biological Process (6): 5-phosphoribose 1-diphosphate biosynthetic process (GO:0006015), purine nucleotide biosynthetic process (GO:0006164), male gonad development (GO:0008584), ribonucleoside monophosphate biosynthetic process (GO:0009156), nucleobase-containing compound metabolic process (GO:0006139), nucleotide biosynthetic process (GO:0009165)

GO Molecular Function (8): magnesium ion binding (GO:0000287), ribose phosphate diphosphokinase activity (GO:0004749), ATP binding (GO:0005524), kinase activity (GO:0016301), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): ribose phosphate diphosphokinase complex (GO:0002189), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Pentose phosphate pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribose phosphate biosynthetic process	1
5-phosphoribose 1-diphosphate metabolic process	1
purine nucleotide metabolic process	1
nucleotide biosynthetic process	1
purine-containing compound biosynthetic process	1
gonad development	1
development of primary male sexual characteristics	1
nucleoside monophosphate biosynthetic process	1
primary metabolic process	1
nucleotide metabolic process	1
nucleoside phosphate biosynthetic process	1
metal ion binding	1
diphosphotransferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cation binding	1
transferase complex, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPS1L1	MSMB	P08118	926
PRPS1L1	NT5C3A	Q9H0P0	778
PRPS1L1	MID2	Q9UJV3	775
PRPS1L1	UMPS	P11172	763
PRPS1L1	COL4A6	Q14031	750
PRPS1L1	SMPX	Q9UHP9	717
PRPS1L1	POU3F4	P49335	692
PRPS1L1	NT5C	Q8TCD5	686
PRPS1L1	APRT	P07741	634
PRPS1L1	HPRT1	P00492	629
PRPS1L1	AIFM1	O95831	616
PRPS1L1	ADSL	P30566	611
PRPS1L1	PPAT	Q06203	602
PRPS1L1	NT5C2	P49902	601
PRPS1L1	RPIA	P49247	593
PRPS1L1	GART	P22102	593

IntAct

27 interactions, top by confidence:

A	B	Type	Score
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
PRPS1	NMT2	psi-mi:“MI:0914”(association)	0.640
PRPSAP2	CCNB1	psi-mi:“MI:0914”(association)	0.530
PRPSAP2	PRPS2	psi-mi:“MI:0914”(association)	0.530
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
rep	PRPS1L1	psi-mi:“MI:0915”(physical association)	0.400
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PRPS2	ARHGEF37	psi-mi:“MI:0914”(association)	0.350
FOXF2	POTEF	psi-mi:“MI:0914”(association)	0.350
PODXL	LGALS8	psi-mi:“MI:0914”(association)	0.350
NXPH1	RAD51C	psi-mi:“MI:0914”(association)	0.350
FTH1	DHX16	psi-mi:“MI:0914”(association)	0.350
NIPSNAP3B	CLUH	psi-mi:“MI:0914”(association)	0.350
KLK5	LRP5	psi-mi:“MI:0914”(association)	0.350
IL22RA2	PTPRF	psi-mi:“MI:0914”(association)	0.350
RASL11A	MBL2	psi-mi:“MI:0914”(association)	0.350
DHFR2	FGFR1	psi-mi:“MI:0914”(association)	0.350
PPIAL4G	YES1	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
PRPS1	MGAM	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Proximity Label-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS)

ESM2 similar proteins: B9KPJ0, O94413, P09330, P11908, P21108, P38063, P38620, P38689, P46585, P60891, P60892, P65234, P65235, P65239, P65240, Q1LTH2, Q2HJ58, Q4R4R7, Q4R4U3, Q54PA9, Q55848, Q5R8F8, Q5RFJ7, Q5XGI0, Q5ZI49, Q7MT83, Q7NQS9, Q7U7L5, Q7UPM4, Q7VFY9, Q7ZXC9, Q82TQ4, Q83AQ1, Q87A22, Q88VA5, Q8DWM2, Q8FZF0, Q8K9X2, Q8KCQ2, Q8PC63

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

195 predictions. Top by Δscore:

Variant	Effect	Δscore
7:18026971:A:AC	donor_gain	0.6300
7:18026972:C:CC	donor_gain	0.6300
7:18026973:T:TT	donor_gain	0.6200
7:18026975:C:CT	donor_gain	0.5800
7:18027181:T:TA	donor_gain	0.5600
7:18026942:T:C	donor_gain	0.5500
7:18027030:T:TA	donor_gain	0.5500
7:18027163:A:AC	donor_gain	0.5300
7:18027480:AT:A	donor_gain	0.5300
7:18026917:A:AC	donor_gain	0.5200
7:18026918:C:CC	donor_gain	0.5200
7:18026975:CCA:C	donor_gain	0.5200
7:18027194:T:TA	donor_gain	0.5200
7:18026918:CT:C	donor_gain	0.5000
7:18026976:CAC:C	donor_gain	0.5000
7:18027148:T:C	donor_gain	0.5000
7:18027489:AT:A	donor_gain	0.5000
7:18026950:T:C	donor_gain	0.4900
7:18027153:A:C	donor_gain	0.4900
7:18027154:T:TA	donor_gain	0.4900
7:18027693:C:CT	donor_gain	0.4900
7:18027098:T:TC	acceptor_gain	0.4800
7:18027176:C:CT	donor_gain	0.4700
7:18027230:A:C	donor_gain	0.4700
7:18027692:C:CT	donor_gain	0.4700
7:18027195:C:A	donor_gain	0.4600
7:18027053:CT:C	donor_gain	0.4500
7:18027160:A:AC	donor_gain	0.4500
7:18027161:C:CC	donor_gain	0.4500
7:18027046:G:C	donor_gain	0.4400

AlphaMissense

2115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:18026877:T:A	R302S	0.995
7:18026877:T:G	R302S	0.995
7:18026844:G:C	F313L	0.994
7:18026844:G:T	F313L	0.994
7:18026846:A:G	F313L	0.994
7:18026888:C:G	A299P	0.994
7:18026878:C:G	R302T	0.992
7:18027372:A:C	F137L	0.992
7:18027372:A:T	F137L	0.992
7:18027374:A:G	F137L	0.992
7:18026884:A:T	I300K	0.989
7:18027520:A:T	V88D	0.989
7:18026848:A:G	L312P	0.988
7:18027377:C:G	G136R	0.986
7:18027349:A:G	L145S	0.984
7:18026881:C:G	R301T	0.983
7:18026884:A:C	I300R	0.983
7:18026894:C:G	A297P	0.983
7:18027369:A:C	F138L	0.983
7:18027369:A:T	F138L	0.983
7:18027371:A:G	F138L	0.983
7:18027678:G:C	F35L	0.983
7:18027678:G:T	F35L	0.983
7:18027680:A:G	F35L	0.983
7:18026880:C:A	R301S	0.982
7:18026880:C:G	R301S	0.982
7:18027280:A:T	V168D	0.982
7:18027554:A:G	C77R	0.982
7:18026878:C:A	R302I	0.981
7:18026881:C:A	R301M	0.981

dbSNP variants (sampled 300 via entrez): RS1000619977 (7:18028436 C>T), RS1001777858 (7:18029248 A>T), RS1002557685 (7:18027798 G>A), RS1003500304 (7:18028414 A>G), RS1003827148 (7:18026553 A>G), RS1005083434 (7:18028782 G>A), RS1007673742 (7:18026941 A>C,G), RS1008273567 (7:18026463 A>C,G), RS1009646852 (7:18026580 C>T), RS1010654772 (7:18028132 A>G), RS1010717541 (7:18029556 A>C,G), RS1011660288 (7:18029219 C>T), RS1012332615 (7:18026954 G>C,T), RS1012489331 (7:18026591 A>G), RS1013221259 (7:18028023 A>G)

Disease associations

OMIM: gene MIM:611566 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002147_21	Fibrinogen	5.000000e-10
GCST004121_31	Fibrinogen levels	1.000000e-12
GCST004122_5	Fibrinogen levels	1.000000e-11
GCST010320_84	PR interval	1.000000e-09
GCST010321_30	PR interval	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	decreases expression	1
bisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
bisphenol AF	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Tamoxifen	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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