ribose-5-P isomerase deficiency

Summary

ribose-5-P isomerase deficiency (MONDO:0012073) is a disease caused by RPIA (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: RPIA (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 38

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	ribose-5-P isomerase deficiency
Mondo ID	MONDO:0012073
MeSH	C563212
OMIM	608611
Orphanet	440706
SNOMED CT	124667004
UMLS	C1291609
MedGen	220946
GARD	0017747
Is cancer (heuristic)	no

Data availability: 38 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › ribose-5-P isomerase deficiency

Related subtypes (64): Alexander disease, cerebrotendinous xanthomatosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, dermatoleukodystrophy, Krabbe disease, Sjogren-Larsson syndrome, Canavan disease, Pelizaeus-Merzbacher spectrum disorder, hereditary spastic paraplegia 2, megalencephalic leukoencephalopathy with subcortical cysts, hypomyelinating leukodystrophy 5, leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome, hypomyelinating leukodystrophy 6, cystic leukoencephalopathy without megalencephaly, sterol carrier protein 2 deficiency, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, hypomyelination with brain stem and spinal cord involvement and leg spasticity, leukoencephalopathy with mild cerebellar ataxia and white matter edema, progressive encephalopathy with leukodystrophy due to DECR deficiency, hypomyelinating leukodystrophy 9, multiple mitochondrial dysfunctions syndrome 4, hypomyelinating leukodystrophy 10, hypomyelinating leukodystrophy 12, hypomyelinating leukodystrophy 13, leukoencephalopathy with bilateral anterior temporal lobe cysts, progressive cavitating leukoencephalopathy, Pelizaeus-Merzbacher-like disease, CADDS, adrenoleukodystrophy, non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy, Aicardi-Goutieres syndrome, metachromatic leukodystrophy, peroxisome biogenesis disorder, unknown leukodystrophy, ravine syndrome, leukodystrophy, hypomyelinating, 22, leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, leukodystrophy, hypomyelinating, 18, leukodystrophy, hypomyelinating, 19, transient infantile, spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 14, leukodystrophy, hypomyelinating, 20, early-onset calcifying leukoencephalopathy-skeletal dysplasia, c11orf73-related autosomal recessive hypomyelinating leukodystrophy, alkaline ceramidase 3 deficiency, leukodystrophy, hypomyelinating, 15, leukodystrophy, hypomyelinating, 16, leukodystrophy, hypomyelinating, 17, POLR-related leukodystrophy, leukoencephalopathy, diffuse hereditary, with spheroids 1, leukoencephalopathy with vanishing white matter, leukodystrophy, hypomyelinating, 24, leukodystrophy, childhood-onset, remitting, leukodystrophy, hypomyelinating, 25, leukodystrophy, hypomyelinating, 26, with chondrodysplasia, adult-onset progressive leukoencephalopathy-early-onset deafness, leukoencephalopathy, porphyria-related, episodic memory defect leukoencephalopathy, leukodystrophy, hypomyelinating, 28, leukodystrophy, demyelinating, adult-onset, leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy, leukoencephalopathy without lacunae, adult-onset, AARS1-related leukoencephalopathy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

38 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 5 pathogenic, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 3 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13007	NM_144563.3(RPIA):c.762del (p.Asn255fs)	RPIA	Pathogenic	no assertion criteria provided
13008	NM_144563.3(RPIA):c.404C>T (p.Ala135Val)	RPIA	Pathogenic	no assertion criteria provided
1683399	NM_144563.3(RPIA):c.451C>T (p.Arg151Ter)	RPIA	Pathogenic	criteria provided, multiple submitters, no conflicts
2682322	NM_144563.3(RPIA):c.679C>T (p.Arg227Ter)	RPIA	Pathogenic	criteria provided, single submitter
928791	NM_144563.3(RPIA):c.347-1G>A	RPIA	Pathogenic	criteria provided, single submitter
1332818	NM_144563.3(RPIA):c.770T>C (p.Ile257Thr)	RPIA	Likely pathogenic	criteria provided, single submitter
635118	NM_144563.3(RPIA):c.627G>C (p.Trp209Cys)	RPIA	Likely pathogenic	criteria provided, single submitter
928792	NM_144563.3(RPIA):c.253G>A (p.Ala85Thr)	RPIA	Likely pathogenic	criteria provided, single submitter
337431	NM_144563.3(RPIA):c.527+11T>C	RPIA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897554	NM_144563.3(RPIA):c.5A>G (p.Gln2Arg)	RPIA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897555	NM_144563.3(RPIA):c.57C>T (p.Pro19=)	RPIA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
898709	NM_144563.3(RPIA):c.789C>T (p.Asp263=)	RPIA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337428	NM_144563.3(RPIA):c.55C>A (p.Pro19Thr)	LOC129934277	Uncertain significance	criteria provided, single submitter
337429	NM_144563.3(RPIA):c.218C>G (p.Ser73Cys)	RPIA	Uncertain significance	criteria provided, single submitter
337430	NM_144563.3(RPIA):c.493G>A (p.Val165Ile)	RPIA	Uncertain significance	criteria provided, single submitter
337432	NM_144563.3(RPIA):c.596+5A>C	RPIA	Uncertain significance	criteria provided, single submitter
337434	NM_144563.3(RPIA):c.706G>A (p.Val236Met)	RPIA	Uncertain significance	criteria provided, multiple submitters, no conflicts
337437	NM_144563.3(RPIA):c.*15G>A	RPIA	Uncertain significance	criteria provided, single submitter
337438	NM_144563.3(RPIA):c.*256C>T	RPIA	Uncertain significance	criteria provided, multiple submitters, no conflicts
337442	NM_144563.3(RPIA):c.*712T>C	RPIA	Uncertain significance	criteria provided, single submitter
337443	NM_144563.3(RPIA):c.*807C>G	RPIA	Uncertain significance	criteria provided, single submitter
895734	NM_144563.3(RPIA):c.*29T>G	RPIA	Uncertain significance	criteria provided, multiple submitters, no conflicts
895735	NM_144563.3(RPIA):c.*134A>C	RPIA	Uncertain significance	criteria provided, single submitter
895737	NM_144563.3(RPIA):c.*281A>G	RPIA	Uncertain significance	criteria provided, single submitter
896016	NM_144563.3(RPIA):c.*558G>A	RPIA	Uncertain significance	criteria provided, single submitter
896017	NM_144563.3(RPIA):c.*591G>T	RPIA	Uncertain significance	criteria provided, single submitter
896018	NM_144563.3(RPIA):c.*635A>G	RPIA	Uncertain significance	criteria provided, single submitter
896019	NM_144563.3(RPIA):c.*728T>C	RPIA	Uncertain significance	criteria provided, single submitter
896020	NM_144563.3(RPIA):c.*783A>G	RPIA	Uncertain significance	criteria provided, single submitter
897553	NM_144563.3(RPIA):c.-17C>A	RPIA	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPIA	Orphanet:440706	Ribose-5-P isomerase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPIA	HGNC:10297	ENSG00000153574	P49247	Ribose-5-phosphate isomerase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPIA	Ribose-5-phosphate isomerase	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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPIA	Enzyme (other)	yes	5.3.1.6	Ribose5P_isomerase_type_A, Ribose5P_isomerase_typA_subgr, NagB/RpiA_transferase-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPIA	285	ubiquitous	marker	secondary oocyte, oocyte, bone marrow

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPIA	2,608

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RPIA	P49247	84.97

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RPIA deficiency: failed conversion of R5P to RU5P	1	11420.0×	4e-04	RPIA
RPIA deficiency: failed conversion of RU5P to R5P	1	11420.0×	4e-04	RPIA
Pentose phosphate pathway disease	1	5710.0×	5e-04	RPIA
Pentose phosphate pathway	1	951.7×	0.002	RPIA
Diseases of carbohydrate metabolism	1	815.7×	0.002	RPIA
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.012	RPIA
Diseases of metabolism	1	80.4×	0.016	RPIA
Disease	1	13.1×	0.086	RPIA
Metabolism	1	11.6×	0.086	RPIA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
D-ribose metabolic process	1	16852.0×	2e-04	RPIA
pentose-phosphate shunt, non-oxidative branch	1	2808.7×	5e-04	RPIA
pentose-phosphate shunt	1	1532.0×	7e-04	RPIA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPIA	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	RPIA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RPIA	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RPIA	5.3.1.6	ribose-5-phosphate isomerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	RPIA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	RPIA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.