Sideroblastic anemia

disease

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Also known as anaemia sideroblasticanemia sideroblastic

Summary

Sideroblastic anemia (MONDO:0015194) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include fludarabine phosphate and treosulfan.

At a glance

Prevalence: Unknown (Worldwide)
Cohort genes: 1
ClinVar variants: 8
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sideroblastic anemia
Mondo ID	MONDO:0015194
MeSH	D000756
Orphanet	1047
DOID	DOID:8955
NCIT	C36078
SNOMED CT	41841004
UMLS	C0002896
MedGen	8067
GARD	0018714
MedDRA	10040661
Is cancer (heuristic)	no

Also known as: anaemia sideroblastic · anemia sideroblastic · sideroblastic anemia

Data availability: 8 ClinVar variants · 2 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › sideroblastic anemia

Subtypes (3): pyridoxine-responsive sideroblastic anemia, myelodysplastic syndrome with ring sideroblasts, inherited sideroblastic anemia

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

8 retrieved; paginated sample, class counts are floors:

6 benign/likely benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
138857	NM_025215.6(PUS1):c.345C>T (p.Asp115=)	LOC132090059	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138859	NM_025215.6(PUS1):c.397G>A (p.Asp133Asn)	LOC132090059	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138853	NM_025215.6(PUS1):c.999G>C (p.Leu333=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138854	NM_025215.6(PUS1):c.1197C>T (p.Phe399=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138858	NM_025215.6(PUS1):c.364C>A (p.Arg122=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
215035	NM_025215.6(PUS1):c.621G>A (p.Thr207=)	PUS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
512031	NM_025215.6(PUS1):c.1065G>T (p.Pro355=)	PUS1	Likely benign	criteria provided, multiple submitters, no conflicts
721364	NM_025215.6(PUS1):c.1047C>T (p.Asn349=)	PUS1	Likely benign	criteria provided, multiple submitters, no conflicts

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
PUS1	Orphanet:2598	Mitochondrial myopathy and sideroblastic 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
PUS1	HGNC:15508	ENSG00000177192	Q9Y606	Pseudouridylate synthase 1 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PUS1	Pseudouridylate synthase 1 homolog	Pseudouridylate synthase that catalyzes pseudouridylation of tRNAs and mRNAs.

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)
PUS1	Enzyme (other)	yes	5.4.99.B22	PsdUridine_synth_TruA, TruA/RsuA/RluB/E/F_N, PsdUridine_synth_TruA_C

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
lower esophagus mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PUS1	229	ubiquitous	marker	granulocyte, mucosa of transverse colon, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PUS1	2,688

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PUS1	Q9Y606	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
tRNA modification in the mitochondrion	1	1038.2×	0.002	PUS1
tRNA modification in the nucleus and cytosol	1	292.8×	0.003	PUS1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial tRNA pseudouridine synthesis	1	5617.3×	0.001	PUS1
tRNA pseudouridine synthesis	1	2808.7×	0.001	PUS1
mRNA pseudouridine synthesis	1	1685.2×	0.001	PUS1
RNA splicing	1	88.2×	0.015	PUS1
mRNA processing	1	78.8×	0.015	PUS1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	PUS1

Therapeutics

Drug target analysis

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

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
PUS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PUS1	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PUS1	5.4.99.B22

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

0 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.

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	0
C	Druggable family + PDB, no drug	1	PUS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PUS1	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT06213402	Not specified	RECRUITING	RADeep Multicenter European Epidemiological Platform for Patients Diagnosed With Rare Anemia Disorders (RADs)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	1
TREOSULFAN	4	1

Cohort genes: PUS1
Drugs: Fludarabine Phosphate, Treosulfan