Congenital dyserythropoietic anemia

Summary

Congenital dyserythropoietic anemia (MONDO:0019403) is a disease (an umbrella term covering 9 Mondo subtypes) with 4 cohort genes and 5 clinical trials. Top therapeutic interventions include zoledronic acid anhydrous.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 4
• ClinVar variants: 4
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		740	Worldwide	Validated
Point prevalence	1-9 / 1 000 000		Worldwide	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated
Prevalence at birth	1-9 / 1 000 000	0.16	Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital dyserythropoietic anemia
Mondo ID	MONDO:0019403
MeSH	D000742
OMIM	224120
Orphanet	85
DOID	DOID:1338
ICD-10-CM	D64.4
ICD-11	899830967
NCIT	C84646
SNOMED CT	52951008
UMLS	C0002876
MedGen	8064
GARD	0001999
Is cancer (heuristic)	no

Also known as: anemia, congenital dyserythropoietic · CDA · congenital dyshaematopoietic anaemia · congenital dyshaematopoietic anemia · dyserythropoietic anemia, congenital

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › congenital dyserythropoietic anemia

Related subtypes (22): congenital nonspherocytic hemolytic anemia, elliptocytosis 2, southeast Asian ovalocytosis, overhydrated hereditary stomatocytosis, cryohydrocytosis, dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, abetalipoproteinemia, hemolytic anemia due to diphosphoglycerate mutase deficiency, glycogen storage disease VII, cutaneous porphyria, hereditary cryohydrocytosis with reduced stomatin, familial pseudohyperkalemia, renal tubular acidosis, distal, 4, with hemolytic anemia, elliptocytosis 1, glycogen storage disease due to aldolase A deficiency, primary CD59 deficiency, triosephosphate isomerase deficiency, dehydrated hereditary stomatocytosis 2, Rh deficiency syndrome, hereditary spherocytosis, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

Subtypes (9): congenital dyserythropoietic anemia type 3, congenital dyserythropoietic anemia type 2, X-linked dyserythropoetic anemia with abnormal platelets and neutropenia, pancreatic insufficiency-anemia-hyperostosis syndrome, congenital dyserythropoietic anemia type 4, thrombocytopenia with congenital dyserythropoietic anemia, congenital dyserythropoietic anemia type 1, Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive, anemia, congenital dyserythropoietic, type IVb

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2498182	NM_016123.4(IRAK4):c.161+1G>A	IRAK4	Likely pathogenic	criteria provided, single submitter
666985	NM_006363.6(SEC23B):c.1079del (p.Leu360fs)	SEC23B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2498181	NM_016123.4(IRAK4):c.86A>C (p.Gln29Pro)	IRAK4	Uncertain significance	criteria provided, single submitter
2498175	NM_173469.4(UBE2Q2):c.884+2293G>A	UBE2Q2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 4 · 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
CDAN1	Definitive	Autosomal recessive	anemia, congenital dyserythropoietic, type 1a	4
SEC23B	Definitive	Autosomal recessive	congenital dyserythropoietic anemia type 2	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEC23B	Orphanet:201	Cowden syndrome
SEC23B	Orphanet:98873	Congenital dyserythropoietic anemia type II
CDAN1	Orphanet:98869	Congenital dyserythropoietic anemia type I
IRAK4	Orphanet:70592	Transient predisposition to invasive pyogenic bacterial infection

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SEC23B	HGNC:10702	ENSG00000101310	Q15437	Protein transport protein Sec23B	gencc,clinvar
CDAN1	HGNC:1713	ENSG00000140326	Q8IWY9	Codanin-1	gencc
IRAK4	HGNC:17967	ENSG00000198001	Q9NWZ3	Interleukin-1 receptor-associated kinase 4	clinvar
UBE2Q2	HGNC:19248	ENSG00000140367	Q8WVN8	Ubiquitin-conjugating enzyme E2 Q2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEC23B	Protein transport protein Sec23B	Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
CDAN1	Codanin-1	May act as a negative regulator of ASF1 in chromatin assembly.
IRAK4	Interleukin-1 receptor-associated kinase 4	Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens.
UBE2Q2	Ubiquitin-conjugating enzyme E2 Q2	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	6.9×	0.538
Enzyme (other)	1	3.0×	0.538
Transcription factor	1	2.1×	0.538
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEC23B	Transcription factor	no		Znf_Sec23_Sec24, Sec23/24_trunk_dom, Sec23/24_helical_dom
CDAN1	Other/Unknown	no		Codanin-1_C, Codanin-1
IRAK4	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Kinase-like_dom_sf
UBE2Q2	Enzyme (other)	yes	2.3.2.23	UBC, RWD_dom, UBQ-conjugating_enzyme/RWD

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
islet of Langerhans	1
parotid gland	1
left ovary	1
sural nerve	1
ventricular zone	1
leukocyte	1
monocyte	1
mononuclear cell	1
oocyte	1
secondary oocyte	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEC23B	289	ubiquitous	marker	endothelial cell, islet of Langerhans, parotid gland
CDAN1	230	ubiquitous	marker	ventricular zone, sural nerve, left ovary
IRAK4	224	ubiquitous	yes	monocyte, mononuclear cell, leukocyte
UBE2Q2	259	ubiquitous	marker	secondary oocyte, oocyte, tibia

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IRAK4	2,977
SEC23B	2,460
CDAN1	1,056
UBE2Q2	737

Intra-cohort edges

A	B	Sources
CDAN1	SEC23B	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IRAK4	Q9NWZ3	96
CDAN1	Q8IWY9	2
UBE2Q2	Q8WVN8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEC23B	Q15437	92.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 4 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
IRAK4 deficiency (TLR5)	1	1427.5×	0.018	IRAK4
Diseases of Immune System	1	439.2×	0.018	IRAK4
Diseases associated with the TLR signaling cascade	1	439.2×	0.018	IRAK4
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	1	439.2×	0.018	IRAK4
IRAK4 deficiency (TLR2/4)	1	285.5×	0.021	IRAK4
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	1	184.2×	0.021	UBE2Q2
Negative regulation of the PI3K/AKT network	1	139.3×	0.021	IRAK4
Interleukin-1 family signaling	1	135.9×	0.021	IRAK4
Toll Like Receptor 10 (TLR10) Cascade	1	107.7×	0.021	IRAK4
Toll Like Receptor 5 (TLR5) Cascade	1	107.7×	0.021	IRAK4
MyD88 cascade initiated on plasma membrane	1	102.0×	0.021	IRAK4
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	95.2×	0.021	IRAK4
MyD88 dependent cascade initiated on endosome	1	95.2×	0.021	IRAK4
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	92.1×	0.021	IRAK4
Toll Like Receptor 9 (TLR9) Cascade	1	87.8×	0.021	IRAK4
Toll Like Receptor TLR6:TLR2 Cascade	1	87.8×	0.021	IRAK4
Toll Like Receptor 2 (TLR2) Cascade	1	86.5×	0.021	IRAK4
Toll Like Receptor TLR1:TLR2 Cascade	1	84.0×	0.021	IRAK4
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	76.1×	0.022	IRAK4
Toll Like Receptor 4 (TLR4) Cascade	1	65.6×	0.023	IRAK4
Toll-like Receptor Cascades	1	62.1×	0.023	IRAK4
Interleukin-1 signaling	1	62.1×	0.023	IRAK4
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.029	IRAK4
Intracellular signaling by second messengers	1	45.7×	0.029	IRAK4
PIP3 activates AKT signaling	1	33.4×	0.038	IRAK4
Signaling by Interleukins	1	32.1×	0.038	IRAK4
Cytokine Signaling in Immune system	1	20.4×	0.057	IRAK4
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.061	UBE2Q2
Innate Immune System	1	12.8×	0.085	IRAK4
Disease	1	6.5×	0.153	IRAK4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Toll signaling pathway	1	601.9×	0.010	IRAK4
import into nucleus	1	601.9×	0.010	CDAN1
interleukin-33-mediated signaling pathway	1	526.6×	0.010	IRAK4
toll-like receptor 9 signaling pathway	1	468.1×	0.010	IRAK4
neutrophil mediated immunity	1	351.1×	0.010	IRAK4
neutrophil migration	1	351.1×	0.010	IRAK4
COPII-coated vesicle cargo loading	1	247.8×	0.012	SEC23B
MyD88-dependent toll-like receptor signaling pathway	1	234.1×	0.012	IRAK4
interleukin-1-mediated signaling pathway	1	200.6×	0.012	IRAK4
toll-like receptor signaling pathway	1	150.5×	0.014	IRAK4
lipopolysaccharide-mediated signaling pathway	1	131.7×	0.014	IRAK4
toll-like receptor 4 signaling pathway	1	131.7×	0.014	IRAK4
positive regulation of smooth muscle cell proliferation	1	82.6×	0.020	IRAK4
JNK cascade	1	68.0×	0.023	IRAK4
protein K48-linked ubiquitination	1	42.1×	0.035	UBE2Q2
cytokine-mediated signaling pathway	1	32.7×	0.042	IRAK4
intracellular protein localization	1	26.2×	0.049	CDAN1
chromatin organization	1	24.8×	0.049	CDAN1
positive regulation of canonical NF-kappaB signal transduction	1	18.2×	0.062	IRAK4
intracellular protein transport	1	16.2×	0.066	SEC23B
intracellular signal transduction	1	9.5×	0.106	IRAK4
innate immune response	1	8.4×	0.114	IRAK4

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
IRAK4	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IRAK4	43	4
SEC23B	0	0
CDAN1	0	0
UBE2Q2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	IRAK4
FEDRATINIB	4	IRAK4
VANDETANIB	4	IRAK4
BOSUTINIB	4	IRAK4
GILTERITINIB	4	IRAK4
NINTEDANIB	4	IRAK4
SUNITINIB	4	IRAK4
DASATINIB	4	IRAK4
QUIZARTINIB	4	IRAK4
CRIZOTINIB	4	IRAK4
GEFITINIB	4	IRAK4
CRENOLANIB	3	IRAK4
LINIFANIB	3	IRAK4
CANERTINIB	3	IRAK4
TESEVATINIB	3	IRAK4
ALVOCIDIB	3	IRAK4
DOVITINIB	3	IRAK4
LESTAURTINIB	3	IRAK4
SU-014813	2	IRAK4
REBASTINIB	2	IRAK4
MK-2461	2	IRAK4
CENISERTIB	2	IRAK4
ILORASERTIB	2	IRAK4
LAUROGUADINE	2	IRAK4
SCH-900776	2	IRAK4
ZIMLOVISERTIB	2	IRAK4
BMS-919373	2	IRAK4
R-406	2	IRAK4
EMAVUSERTIB	2	IRAK4
BI-2536	2	IRAK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
IRAK4	799	Binding:795, Functional:3, ADMET:1
SEC23B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBE2Q2	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
IRAK4	799

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
PONATINIB	4	IRAK4
FEDRATINIB	4	IRAK4
VANDETANIB	4	IRAK4
BOSUTINIB	4	IRAK4
GILTERITINIB	4	IRAK4
NINTEDANIB	4	IRAK4
SUNITINIB	4	IRAK4
DASATINIB	4	IRAK4
QUIZARTINIB	4	IRAK4
CRIZOTINIB	4	IRAK4
GEFITINIB	4	IRAK4
CRENOLANIB	3	IRAK4
LINIFANIB	3	IRAK4
CANERTINIB	3	IRAK4
TESEVATINIB	3	IRAK4
ALVOCIDIB	3	IRAK4
DOVITINIB	3	IRAK4
LESTAURTINIB	3	IRAK4
SU-014813	2	IRAK4
REBASTINIB	2	IRAK4
MK-2461	2	IRAK4
CENISERTIB	2	IRAK4
ILORASERTIB	2	IRAK4
LAUROGUADINE	2	IRAK4
SCH-900776	2	IRAK4
ZIMLOVISERTIB	2	IRAK4
BMS-919373	2	IRAK4
R-406	2	IRAK4
EMAVUSERTIB	2	IRAK4
BI-2536	2	IRAK4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	IRAK4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	UBE2Q2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SEC23B, CDAN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SEC23B	1	—
CDAN1	0	—
UBE2Q2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07471516	PHASE1/PHASE2	RECRUITING	Zoledronic Acid Treatment in Patients With Congenital Dyserythropoietic Anemia
NCT02964494	Not specified	RECRUITING	The Congenital Dyserythropoietic Anemia Registry (CDAR)
NCT06213402	Not specified	RECRUITING	RADeep Multicenter European Epidemiological Platform for Patients Diagnosed With Rare Anemia Disorders (RADs)
NCT07206095	Not specified	RECRUITING	Integrative Diagnosis for SCD and Other RADs
NCT03983629	Not specified	UNKNOWN	Registry of Congenital Dyserythropoietic Anemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ZOLEDRONIC ACID ANHYDROUS	4	1