RPIA

Summary

RPIA (ribose 5-phosphate isomerase A, HGNC:10297) is a protein-coding gene on chromosome 2p11.2, encoding Ribose-5-phosphate isomerase (P49247). Catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate and participates in the first step of the non-oxidative branch of the pentose phosphate pathway. It is a selective cancer dependency (DepMap: 27.6% of cell lines).

The protein encoded by this gene is an enzyme, which catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate in the pentose-phosphate pathway. This gene is highly conserved in most organisms. The enzyme plays an essential role in the carbohydrate metabolism. Mutations in this gene cause ribose 5-phosphate isomerase deficiency. A pseudogene is found on chromosome 18.

Source: NCBI Gene 22934 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ribose-5-P isomerase deficiency (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 123 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 25
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 27.6% of screened cell lines
• MANE Select transcript: NM_144563

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10297
Approved symbol	RPIA
Name	ribose 5-phosphate isomerase A
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153574
Ensembl biotype	protein_coding
OMIM	180430
Entrez	22934

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000283646, ENST00000871058, ENST00000871059, ENST00000871060, ENST00000915183, ENST00000915184

RefSeq mRNA: 1 — MANE Select: NM_144563 NM_144563

CCDS: CCDS2004

Canonical transcript exons

ENST00000283646 — 9 exons

Exon	Start	End
ENSE00001011505	88729278	88729337
ENSE00001144217	88691673	88691983
ENSE00001158224	88737977	88738076
ENSE00001158232	88736535	88736676
ENSE00001158237	88735669	88735737
ENSE00001158247	88734552	88734616
ENSE00001158260	88700009	88700064
ENSE00001158266	88698484	88698544
ENSE00001182788	88749981	88750929

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 97.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3231 / max 636.1770, expressed in 1772 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21355	6.5209	1684
21356	2.0539	936
21359	1.8023	739
21358	0.8353	469
21357	0.7520	393
21362	0.2063	11
21360	0.1049	39
21363	0.0473	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.28	gold quality
oocyte	CL:0000023	96.26	gold quality
bone marrow	UBERON:0002371	94.35	gold quality
esophagus squamous epithelium	UBERON:0006920	93.89	gold quality
trabecular bone tissue	UBERON:0002483	93.84	gold quality
lower esophagus mucosa	UBERON:0035834	92.14	gold quality
monocyte	CL:0000576	92.03	gold quality
mononuclear cell	CL:0000842	92.03	gold quality
epithelium of esophagus	UBERON:0001976	91.83	gold quality
leukocyte	CL:0000738	91.82	gold quality
mucosa of transverse colon	UBERON:0004991	91.41	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.95	gold quality
amniotic fluid	UBERON:0000173	90.64	gold quality
thymus	UBERON:0002370	90.46	gold quality
squamous epithelium	UBERON:0006914	89.69	gold quality
placenta	UBERON:0001987	89.67	gold quality
bone marrow cell	CL:0002092	89.37	gold quality
rectum	UBERON:0001052	89.33	gold quality
endometrium	UBERON:0001295	89.02	gold quality
lymph node	UBERON:0000029	88.66	gold quality
gastrocnemius	UBERON:0001388	88.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.31	gold quality
deltoid	UBERON:0001476	88.26	gold quality
biceps brachii	UBERON:0001507	88.25	gold quality
blood	UBERON:0000178	88.23	gold quality
esophagus mucosa	UBERON:0002469	88.13	gold quality
muscle of leg	UBERON:0001383	88.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.79	gold quality
nasal cavity epithelium	UBERON:0005384	87.78	gold quality
colonic mucosa	UBERON:0000317	87.72	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	10.92
E-ANND-3	yes	4.46
E-CURD-119	no	413.99
E-GEOD-131882	no	179.09
E-HCAD-10	no	1.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

62 targeting RPIA, 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-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• RPI is the second known inborn error in the reversible phase of the pentose-phosphate-pathway, confirming that defects in pentose and polyol metabolism constitute a new area of inborn metabolic disorders (PMID:14988808)
• Study provides new insight into the molecular mechanisms by which RPIA overexpression can induce oncogenesis in hepatocellular carcinoma. (PMID:25429733)
• In this work, through an in silico comparative analysis between the genomes of Leishmania major and Homo sapiens, the enzyme ribose 5-phosphate isomerase (R5PI) was indicated as a promising molecular target. (PMID:25528729)
• CRC cells that overexpressed miR124 or with knockdown of RPIA or PRPS1 had reduced DNA synthesis and proliferation, whereas cells incubated with an inhibitor of miR124 had significantly increased DNA synthesis and proliferation and formed more colonies. (PMID:26248089)
• The results are consistent with a model in which RPIA suppresses autophagy and LC3 processing by modulation of redox signaling. (PMID:27328773)
• SRC-2 controls the pentose phosphate pathway through RPIA in human endometrial cancer cells. (PMID:30177747)
• We report on a subject with RPIA associated progressive leukoencephalopathy with elevated urine arabitol and ribitol levels and a novel missense variant c.770T>C p.(Ile257Thr) in exon 8 of RPIA. We also compare the phenotypes of all the four subjects. Our report confirms the phenotype and the genetic cause of this condition. (PMID:31247379)
• Suppression of Ribose-5-Phosphate Isomerase a Induces ROS to Activate Autophagy, Apoptosis, and Cellular Senescence in Lung Cancer. (PMID:35887232)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpia	ENSDARG00000056640
mus_musculus	Rpia	ENSMUSG00000053604
rattus_norvegicus	Rpia	ENSRNOG00000005576
drosophila_melanogaster	Rpi	FBGN0050410
caenorhabditis_elegans		WBGENE00015101

Protein

Protein identifiers

Ribose-5-phosphate isomerase — P49247 (reviewed: P49247)

Alternative names: Phosphoriboisomerase

All UniProt accessions (1): P49247

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate and participates in the first step of the non-oxidative branch of the pentose phosphate pathway.

Disease relevance. Ribose 5-phosphate isomerase deficiency (RPIAD) [MIM:608611] An autosomal recessive inborn error of polyols metabolism characterized by highly elevated level of ribitol and arabitol in brain and body fluids. Clinical features include leukoencephalopathy, psychomotor retardation from early life, neurologic regression, and a mild sensorimotor neuropathy. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Carbohydrate degradation; pentose phosphate pathway; D-ribose 5-phosphate from D-ribulose 5-phosphate (non-oxidative stage): step 1/1.

Similarity. Belongs to the ribose 5-phosphate isomerase family.

RefSeq proteins (1): NP_653164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004788	Ribose5P_isomerase_type_A	Family
IPR020672	Ribose5P_isomerase_typA_subgr	Family
IPR037171	NagB/RpiA_transferase-like	Homologous_superfamily

Pfam: PF06026

Enzyme classification (BRENDA):

• EC 5.3.1.6 — ribose-5-phosphate isomerase (BRENDA: 44 organisms, 165 substrates, 87 inhibitors, 100 Km, 73 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-RIBOSE 5-PHOSPHATE	0.017–37	40
D-ALLOSE	3.8–460	13
D-PSICOSE	43–78	9
D-RIBOSE	44–270	6
D-RIBOSE-5-PHOSPHATE	0.52–4.41	5
D-RIBULOSE 5-PHOSPHATE	0.015–15	4
D-RIBOSE 5-DIPHOSPHATE	2–10	3
D-RIBULOSE 5-DIPHOSPHATE	1.4–2.5	2
L-TALOSE	37–190	2
D-RIBULOSE	34	1
D-TALOSE	232	1
L-ALLOSE	98	1
L-RHAMNOSE	43.47	1
L-RIBOSE	173	1
L-RIBULOSE	319	1

Catalyzed reactions (Rhea), 1 shown:

• aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate (RHEA:14657)

UniProt features (9 total): compositionally biased region 2, modified residue 2, sequence conflict 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49247-F1	84.97	0.77

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 (2): 52, 106

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5659996	RPIA deficiency: failed conversion of R5P to RU5P
R-HSA-6791461	RPIA deficiency: failed conversion of RU5P to R5P
R-HSA-71336	Pentose phosphate pathway
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-5663084	Diseases of carbohydrate metabolism
R-HSA-5668914	Diseases of metabolism
R-HSA-6791465	Pentose phosphate pathway disease
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 251 (showing top): MORF_DNMT1, GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GGAMTNNNNNTCCY_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLUCOSE_6_PHOSPHATE_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, SCHUHMACHER_MYC_TARGETS_UP, GATA1_01, HEN1_01, WTGAAAT_UNKNOWN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, MORF_PRKDC

GO Biological Process (3): D-ribose metabolic process (GO:0006014), pentose-phosphate shunt (GO:0006098), pentose-phosphate shunt, non-oxidative branch (GO:0009052)

GO Molecular Function (6): ribose-5-phosphate isomerase activity (GO:0004751), identical protein binding (GO:0042802), monosaccharide binding (GO:0048029), protein binding (GO:0005515), isomerase activity (GO:0016853), carbohydrate binding (GO:0030246)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Pentose phosphate pathway disease	2
Metabolism of carbohydrates and carbohydrate derivatives	1
Diseases of metabolism	1
Disease	1
Diseases of carbohydrate metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
cytoplasm	2
pentose metabolic process	1
NADPH regeneration	1
pentose-phosphate shunt, oxidative branch	1
pentose-phosphate shunt, non-oxidative branch	1
glucose 6-phosphate metabolic process	1
D-ribulose-phosphate 3-epimerase activity	1
ribose-5-phosphate isomerase activity	1
transaldolase activity	1
transketolase activity	1
generation of precursor metabolites and energy	1
pentose-phosphate shunt	1
glyceraldehyde-3-phosphate metabolic process	1
intramolecular oxidoreductase activity, interconverting aldoses and ketoses	1
protein binding	1
carbohydrate binding	1
small molecule binding	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPIA	TALDO1	P37837	992
RPIA	RPE	Q96AT9	895
RPIA	TKT	P29401	840
RPIA	RPEL1	Q2QD12	810
RPIA	TKTL2	Q9H0I9	799
RPIA	TKTL1	P51854	799
RPIA	PGD	P52209	793
RPIA	H6PD	O95479	762
RPIA	TPI1	P00938	744
RPIA	GPI	P06744	744
RPIA	PGLS	O95336	743
RPIA	G6PD	P11413	724
RPIA	RBKS	Q9H477	704
RPIA	XYLB	O75191	649
RPIA	PFKM	P08237	647

IntAct

126 interactions, top by confidence:

A	B	Type	Score
NTAQ1	RPIA	psi-mi:“MI:0915”(physical association)	0.830
RPIA	GORASP2	psi-mi:“MI:0915”(physical association)	0.830
RPIA	NTAQ1	psi-mi:“MI:0915”(physical association)	0.830
GORASP2	RPIA	psi-mi:“MI:0915”(physical association)	0.830
RPIA	ATPAF2	psi-mi:“MI:0915”(physical association)	0.810
ATPAF2	RPIA	psi-mi:“MI:0915”(physical association)	0.810
RPIA	LNX1	psi-mi:“MI:0915”(physical association)	0.740
RPIA	CENPP	psi-mi:“MI:0915”(physical association)	0.720
TXN2	RPIA	psi-mi:“MI:0915”(physical association)	0.720
CENPP	RPIA	psi-mi:“MI:0915”(physical association)	0.720
RPIA	TXN2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (98): RPIA (Two-hybrid), RPIA (Two-hybrid), RPIA (Two-hybrid), TXN2 (Two-hybrid), GORASP2 (Two-hybrid), WDYHV1 (Two-hybrid), ATPAF2 (Two-hybrid), FOXP2 (Two-hybrid), CENPP (Two-hybrid), RNF208 (Two-hybrid), RPIA (Affinity Capture-RNA), RPIA (Affinity Capture-RNA), RPIA (Affinity Capture-MS), RPIA (Affinity Capture-MS), RPIA (Affinity Capture-MS)

ESM2 similar proteins: A2TLM1, B4G0F3, B8BKI7, B9N1F9, B9SQI7, C1BJB1, C6JS30, D2XV59, E0CSI1, E9Q4Z2, F4JGR5, O00178, O00763, O04059, O08582, O19069, P0DPI2, P11029, P11497, P13086, P19356, P21343, P22907, P28492, P47968, P49247, P53597, Q13085, Q28559, Q2R483, Q3T186, Q571F8, Q58DC5, Q58DR8, Q5I0K3, Q5NAY4, Q5R8Q7, Q5SWU9, Q5XGS8, Q5ZHY5

Diamond homologs: A1SSJ0, A2C4N6, A2C6S4, A2TLM1, A3PL91, A4FWY7, A4WQX2, A5GNH7, A5GVF8, A5UA25, A5UGX5, A5UXC5, A5VI94, A6U9T4, A6UPJ0, A6UUZ8, A6VGC9, A6VQH4, A7I6S5, A7NNA4, A9AAC4, A9BCI0, A9VID8, A9WIA0, B0R7H0, B0URT3, B1KFT2, B1XL11, B2G5S0, B2S3K6, B7K6D3, B7KIR2, B8FL28, B8GYT0, B8HN58, B9KKA1, B9KYD3, B9LCG3, B9LU09, C1L1P6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RPIA	“down-regulates quantity”	“D-ribulose 5-phosphate”	“chemical modification”
RPIA	“up-regulates quantity”	“D-ribofuranose 5-phosphate(2-)”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of translation	5	21.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	61
Likely benign	30
Benign	7

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
13007	NM_144563.3(RPIA):c.762del (p.Asn255fs)	Pathogenic
13008	NM_144563.3(RPIA):c.404C>T (p.Ala135Val)	Pathogenic
1683399	NM_144563.3(RPIA):c.451C>T (p.Arg151Ter)	Pathogenic
2682322	NM_144563.3(RPIA):c.679C>T (p.Arg227Ter)	Pathogenic
928791	NM_144563.3(RPIA):c.347-1G>A	Pathogenic
1332818	NM_144563.3(RPIA):c.770T>C (p.Ile257Thr)	Likely pathogenic
635118	NM_144563.3(RPIA):c.627G>C (p.Trp209Cys)	Likely pathogenic
928792	NM_144563.3(RPIA):c.253G>A (p.Ala85Thr)	Likely pathogenic

SpliceAI

1144 predictions. Top by Δscore:

Variant	Effect	Δscore
2:88691982:GG:G	donor_gain	1.0000
2:88691983:GG:G	donor_gain	1.0000
2:88698471:C:CA	acceptor_gain	1.0000
2:88698482:A:AG	acceptor_gain	1.0000
2:88698483:G:GG	acceptor_gain	1.0000
2:88735653:T:A	acceptor_gain	1.0000
2:88735664:T:A	acceptor_gain	1.0000
2:88735664:TGCA:T	acceptor_loss	1.0000
2:88735664:TGCAG:T	acceptor_gain	1.0000
2:88735666:CA:C	acceptor_loss	1.0000
2:88735666:CAG:C	acceptor_gain	1.0000
2:88735667:A:AG	acceptor_gain	1.0000
2:88735667:A:T	acceptor_loss	1.0000
2:88735667:AGA:A	acceptor_gain	1.0000
2:88735667:AGAG:A	acceptor_gain	1.0000
2:88735668:G:GC	acceptor_gain	1.0000
2:88735668:GA:G	acceptor_gain	1.0000
2:88735668:GAG:G	acceptor_gain	1.0000
2:88735668:GAGG:G	acceptor_gain	1.0000
2:88735668:GAGGC:G	acceptor_gain	1.0000
2:88735733:TTCAG:T	donor_loss	1.0000
2:88735734:TCAG:T	donor_loss	1.0000
2:88735736:AGGTA:A	donor_loss	1.0000
2:88735737:GGTAC:G	donor_loss	1.0000
2:88735738:GTACA:G	donor_loss	1.0000
2:88736518:T:A	acceptor_gain	1.0000
2:88736531:CCAG:C	acceptor_loss	1.0000
2:88736532:CAGGA:C	acceptor_loss	1.0000
2:88736533:A:AC	acceptor_loss	1.0000
2:88736534:G:GC	acceptor_loss	1.0000

AlphaMissense

2045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:88698506:G:A	G103E	1.000
2:88698512:G:A	G105D	1.000
2:88734601:T:C	L171P	1.000
2:88734606:A:G	K173E	1.000
2:88734608:G:C	K173N	1.000
2:88734608:G:T	K173N	1.000
2:88734609:G:C	G174R	1.000
2:88735686:A:T	E182V	1.000
2:88735687:G:C	E182D	1.000
2:88735687:G:T	E182D	1.000
2:88736537:A:T	K200I	1.000
2:88750001:T:C	F287L	1.000
2:88750003:C:A	F287L	1.000
2:88750003:C:G	F287L	1.000
2:88691944:G:C	K82N	0.999
2:88691944:G:T	K82N	0.999
2:88691964:C:A	A89D	0.999
2:88698500:G:A	G101E	0.999
2:88698505:G:A	G103R	0.999
2:88698505:G:C	G103R	0.999
2:88698506:G:T	G103V	0.999
2:88698508:A:C	S104R	0.999
2:88698510:T:A	S104R	0.999
2:88698510:T:G	S104R	0.999
2:88698511:G:C	G105R	0.999
2:88698511:G:T	G105C	0.999
2:88698512:G:T	G105V	0.999
2:88700044:T:C	C128R	0.999
2:88700051:C:A	P130H	0.999
2:88700057:C:T	S132F	0.999

dbSNP variants (sampled 300 via entrez): RS1000000662 (2:88721740 A>T), RS1000023391 (2:88721617 A>G), RS1000051882 (2:88700387 A>G), RS1000149796 (2:88727896 T>G), RS1000179731 (2:88693861 G>A), RS1000197013 (2:88751239 T>C), RS1000217257 (2:88740903 T>G), RS1000248572 (2:88727708 G>A,C), RS1000257892 (2:88703726 G>C), RS1000376539 (2:88697854 C>T), RS1000391014 (2:88697105 C>A), RS1000451583 (2:88695000 A>G), RS1000659342 (2:88702004 A>G), RS1000676031 (2:88735945 C>T), RS1000700140 (2:88703933 T>C)

Disease associations

OMIM: gene MIM:180430 | disease phenotypes: MIM:608611

GenCC curated gene-disease

Disease	Classification	Inheritance
ribose-5-P isomerase deficiency	Strong	Autosomal recessive

Mondo (1): ribose-5-P isomerase deficiency (MONDO:0012073)

Orphanet (1): Ribose-5-P isomerase deficiency (Orphanet:440706)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001271	Polyneuropathy
HP:0002311	Incoordination
HP:0002352	Leukoencephalopathy
HP:0007141	Sensorimotor neuropathy
HP:0025550	Elevated circulating ribitol concentration
HP:0034894	Elevated brain polyol compounds by MRS
HP:0410055	Decreased level of erythritol in urine
HP:0410056	Decreased CSF erythritol concentration
HP:0410057	Increased level of D-threitol in plasma
HP:0410058	Increased CSF D-threitol concentration
HP:0410059	Increased level of D-threitol in urine
HP:0410070	Increased level of ribitol in urine
HP:0410071	Increased CSF ribitol concentration
HP:0410072	Increased level of ribose in urine
HP:0410073	Increased CSF ribose concentration
HP:0410074	Increased level of xylitol in urine
HP:0410075	Increased CSF xylitol concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_2695	Blood protein levels	2.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563212	Ribose 5-Phosphate Isomerase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725137 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178617: Inhibition of RPIA (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
Testosterone	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
methylselenic acid	decreases expression	1
cobaltous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Rosiglitazone	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Allergens	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697347	Binding	Inhibition of RPIA (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1QE	Abcam K-562 RPIA KO	Cancer cell line	Female
CVCL_D2M0	Abcam Raji RPIA KO	Cancer cell line	Male
CVCL_WQ48	Abcam Jurkat RPIA KO	Cancer cell line	Male

Clinical trials (associated diseases)

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