Myelodysplastic syndrome associated with isolated del(5q)

Summary

Myelodysplastic syndrome associated with isolated del(5q) (MONDO:0007925) is a disease with 1 cohort gene and 12 clinical trials. Top therapeutic interventions include bendamustine hydrochloride, busulfan, and clofarabine.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 18
• Clinical trials: 12

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0002863	Myelodysplasia	Very frequent (80-99%)
HP:0001877	Abnormal erythrocyte morphology	Frequent (30-79%)
HP:0001894	Thrombocytosis	Frequent (30-79%)
HP:0001972	Macrocytic anemia	Frequent (30-79%)
HP:0012133	Erythroid hypoplasia	Frequent (30-79%)
HP:0012143	Abnormal megakaryocyte morphology	Frequent (30-79%)
HP:0025435	Increased circulating lactate dehydrogenase concentration	Frequent (30-79%)
HP:0031020	Bone marrow hypercellularity	Frequent (30-79%)
HP:0031385	Megakaryocyte nucleus hypolobulation	Frequent (30-79%)
HP:0001882	Leukopenia	Occasional (5-29%)
HP:0001892	Abnormal bleeding	Occasional (5-29%)
HP:0004808	Acute myeloid leukemia	Occasional (5-29%)
HP:0005528	Bone marrow hypocellularity	Occasional (5-29%)
HP:0011273	Anisocytosis	Occasional (5-29%)
HP:0011992	Abnormality of neutrophil morphology	Occasional (5-29%)
HP:0012129	Abnormality of bone marrow stromal cells	Occasional (5-29%)
HP:0012148	Multiple lineage myelodysplasia	Occasional (5-29%)
HP:0031035	Chronic infection	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	myelodysplastic syndrome associated with isolated del(5q)
Mondo ID	MONDO:0007925
MeSH	C535323
OMIM	153550
Orphanet	86841
DOID	DOID:0090016
ICD-10-CM	D46.C
ICD-11	420472577
NCIT	C6867
SNOMED CT	277597005
UMLS	C1292779
MedGen	226950
GARD	0008723
Is cancer (heuristic)	no

Also known as: 5q deletion syndrome · 5Q minus syndrome · 5q syndrome · 5Q- syndrome · 5q- syndrome · 5q- syndrome, refractory macrocytic anaemia due to 5q deletion · chromosome 5q deletion syndrome · macrocytic anemia, refractory, due to 5q deletion, somatic · MAR · myelodysplastic syndrome associated with isolated del (5q) chromosome Abnormality · myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality · myelodysplastic syndrome with 5q deletion · myelodysplastic syndrome with isolated del(5q) · refractory macrocytic anaemia due to 5q deletion · refractory macrocytic anemia due to 5q deletion

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › macrocytic anemia › myelodysplastic syndrome associated with isolated del(5q)

Related subtypes (1): megaloblastic 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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3064445	NM_001130053.5(EEF1D):c.1488+1G>A	EEF1D	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
EEF1D	HGNC:3211	ENSG00000104529	P29692	Elongation factor 1-delta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EEF1D	Elongation factor 1-delta	EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.

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)
EEF1D	Other/Unknown	no		Transl_elong_EF1B_B/D_CS, EF1B_bsu/dsu_GNE, Transl_elong_EF1B/ribsomal_bS6

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
apex of heart	1
calcaneal tendon	1
left ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EEF1D	136	ubiquitous	marker	calcaneal tendon, apex of heart, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EEF1D	3,866

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EEF1D	P29692	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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 Elongation	1	278.5×	0.004	EEF1D

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
cytoplasmic translational elongation	1	8426.0×	6e-04	EEF1D
translational elongation	1	1203.7×	0.002	EEF1D
cellular response to ionizing radiation	1	411.0×	0.004	EEF1D
cellular response to heat	1	343.9×	0.004	EEF1D
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	EEF1D

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
EEF1D	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	EEF1D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
EEF1D	8	Binding:8

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	EEF1D

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	EEF1D
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: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	5
Not specified	3
PHASE1/PHASE2	2
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00322101	PHASE3	COMPLETED	Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00004997	PHASE2	COMPLETED	Leucovorin for the Treatment of 5 q Minus Syndrome
NCT00839982	PHASE1/PHASE2	COMPLETED	Clofarabine and Cytarabine in Treating Older Patients With AML or High-Risk MDS
NCT01141725	PHASE1/PHASE2	COMPLETED	Bendamustine and Idarubicin in Treating Older Patients With Previously Untreated AML or MDS
NCT01273766	PHASE2	COMPLETED	Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies
NCT01789255	PHASE2	COMPLETED	Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies
NCT01869114	PHASE2	COMPLETED	Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy
NCT02666950	PHASE2	COMPLETED	WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00890747	PHASE1	COMPLETED	Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy
NCT04869683	Not specified	RECRUITING	Biocollection in MyeloDysplastic Syndrome (P-MDS)
NCT00445744	Not specified	COMPLETED	Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome
NCT04701229	Not specified	UNKNOWN	Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BENDAMUSTINE HYDROCHLORIDE	4	1
BUSULFAN	4	1
CLOFARABINE	4	1
DEFERASIROX	4	1
FLUDARABINE PHOSPHATE	4	1
CHEMBL406352	0	1