Pure red-cell aplasia

Summary

Pure red-cell aplasia (MONDO:0001705) is a disease with 1 cohort gene and 16 clinical trials. Top therapeutic interventions include sirolimus, cyclosporine, and daclizumab.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pure red-cell aplasia
Mondo ID	MONDO:0001705
MeSH	D012010
DOID	DOID:1340
NCIT	C34974
SNOMED CT	50715003
UMLS	C0034902
MedGen	11154
GARD	0007504
NORD	1636
Is cancer (heuristic)	no

Also known as: PRCA · pure red cell aplasia · Pure Red Cell Aplasia, Acquired

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › pure red-cell aplasia

Related subtypes (18): congenital anemia, neonatal anemia, microcytic anemia, hypochromic anemia, pancytopenia, deficiency anemia, macrocytic anemia, normocytic anemia, sideroblastic anemia, aplastic anemia, hemoglobin C disease, hemoglobin E disease, beta-thalassemia and related diseases, hemoglobinopathy Toms River, hereditary methemoglobinemia, hemoglobin D disease, anemia due to enzyme disorder, anemia due to chronic disorder

Subtypes (2): Diamond-Blackfan anemia, adult pure red cell aplasia

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
812897	NM_001029.5(RPS26):c.312+2T>A	RPS26	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS26	Orphanet:124	Diamond-Blackfan anemia

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
RPS26	HGNC:10414	ENSG00000197728	P62854	Small ribosomal subunit protein eS26	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS26	Small ribosomal subunit protein eS26	Component of the small ribosomal subunit.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS26	Other/Unknown	no		Ribosomal_eS26, Ribosomal_eS26_sf, Ribosomal_eS26_CS

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
granulocyte	1
left adrenal gland cortex	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS26	140	ubiquitous	marker	granulocyte, left adrenal gland cortex, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPS26	829

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS26	P62854	190

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. 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
Eukaryotic Translation Initiation	1	308.6×	0.016	RPS26
Cap-dependent Translation Initiation	1	308.6×	0.016	RPS26
SARS-CoV-1 modulates host translation machinery	1	308.6×	0.016	RPS26
Eukaryotic Translation Elongation	1	278.5×	0.016	RPS26
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1	271.9×	0.016	RPS26
Nonsense-Mediated Decay (NMD)	1	233.1×	0.016	RPS26
SARS-CoV-2 modulates host translation machinery	1	223.9×	0.016	RPS26
Influenza Viral RNA Transcription and Replication	1	215.5×	0.016	RPS26
Formation of the ternary complex, and subsequently, the 43S complex	1	215.5×	0.016	RPS26
Selenoamino acid metabolism	1	196.9×	0.016	RPS26
Translation initiation complex formation	1	190.3×	0.016	RPS26
Ribosomal scanning and start codon recognition	1	190.3×	0.016	RPS26
Influenza Infection	1	175.7×	0.016	RPS26
SARS-CoV-1-host interactions	1	175.7×	0.016	RPS26
Cellular response to starvation	1	165.5×	0.016	RPS26
rRNA processing in the nucleus and cytosol	1	160.8×	0.016	RPS26
rRNA processing	1	146.4×	0.016	RPS26
SARS-CoV-1 Infection	1	142.8×	0.016	RPS26
Peptide chain elongation	1	126.9×	0.016	RPS26
Viral mRNA Translation	1	126.9×	0.016	RPS26
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.016	RPS26
Signaling by ROBO receptors	1	124.1×	0.016	RPS26
Selenocysteine synthesis	1	120.2×	0.016	RPS26
Eukaryotic Translation Termination	1	120.2×	0.016	RPS26
SARS-CoV-2-host interactions	1	119.0×	0.016	RPS26
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.016	RPS26
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.016	RPS26
Formation of a pool of free 40S subunits	1	112.0×	0.016	RPS26
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.016	RPS26
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.016	RPS26

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
negative regulation of RNA splicing	1	2407.4×	0.001	RPS26
cytoplasmic translation	1	185.2×	0.008	RPS26
translation	1	102.8×	0.010	RPS26

Therapeutics

Drugs indicated for this disease

0 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cyclosporine	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bortezomib, Dexamethasone, Isatuximab.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RPS26	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS26	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS26

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPS26	89	Binding:89

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)
GENTAMICIN SULFATE	4	RPS26

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS26
B	Phased (≥1) drug, not yet approved	0
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: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	4
PHASE2	4
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03364764	PHASE4	COMPLETED	Sirolimus Treatment for Refractory PRCA
NCT03540472	PHASE4	UNKNOWN	Tacrolimus Treatment for Refractory PRCA
NCT03918265	PHASE4	UNKNOWN	Tacrolimus Treatment for Refractory Autoimmune Cytopenia
NCT04470804	PHASE4	COMPLETED	Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA
NCT03214354	PHASE2	RECRUITING	Nonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor
NCT00001962	PHASE2	TERMINATED	A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
NCT00004143	PHASE2	COMPLETED	Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes
NCT00314795	PHASE2	COMPLETED	Efficacy and Safety of Peginesatide (AF37702) in the Treatment of Anemia in Participants With Chronic Kidney Disease
NCT01362595	PHASE1/PHASE2	COMPLETED	Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
NCT03966053	PHASE1/PHASE2	TERMINATED	The Use of Trifluoperazine in Transfusion Dependent DBA
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT00004378	Not specified	COMPLETED	Stem Cell Transplantation (SCT) for Genetic Diseases
NCT00006055	Not specified	UNKNOWN	Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases
NCT00211042	Not specified	COMPLETED	A Study of Patients With Pure Red Cell Aplasia Associated With Recombinant Human Erythropoietin Treatment
NCT00211068	Not specified	COMPLETED	A Study of Risk Factors for Anti-erythropoietin Antibody Positive Pure Red Cell Aplasia Among Patients With Chronic Kidney Disease Receiving Epoetin Alfa
NCT00391287	Not specified	COMPLETED	Surveillance Study to Estimate the Incidence of Pure Red Blood Cell Aplasia Among Patients With Chronic Kidney Failure

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SIROLIMUS	4	3
CYCLOSPORINE	4	1
DACLIZUMAB	4	1
PEGINESATIDE	4	1
TRIFLUOPERAZINE	4	1
LEUCINE	3	1