Congenital dyserythropoietic anemia type 1

Summary

Congenital dyserythropoietic anemia type 1 (MONDO:0020337) is a disease with 2 cohort genes and 1 clinical trial. Top therapeutic interventions include esomeprazole and omeprazole.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 153
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-9 / 1 000 000	0.5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital dyserythropoietic anemia type 1
Mondo ID	MONDO:0020337
Orphanet	98869
DOID	DOID:0111396
SNOMED CT	59548005
UMLS	C0271933
MedGen	82891
GARD	0002000
Is cancer (heuristic)	no

Also known as: anemia, dyserythropoietic, congenital type 1 · CDA I · CDA type 1 · CDA type I · congenital dyserythropoietic anemia type 1 · dyserythropoietic anemia, congenital type 1 · type I congenital dyserythropoietic anaemia · type I congenital dyserythropoietic anemia

Data availability: 153 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › congenital dyserythropoietic anemia type 1

Related subtypes (7): myopathy, lactic acidosis, and sideroblastic anemia, congenital nonspherocytic hemolytic anemia, congenital dyserythropoietic anemia type 3, congenital dyserythropoietic anemia type 2, congenital dyserythropoietic anemia type 4, severe congenital hypochromic anemia with ringed sideroblasts, Fanconi anemia

Subtypes (2): anemia, congenital dyserythropoietic, type 1a, congenital dyserythropoietic anemia type type 1B

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

153 retrieved; paginated sample, class counts are floors:

71 uncertain significance, 37 conflicting classifications of pathogenicity, 20 benign, 13 benign/likely benign, 5 pathogenic/likely pathogenic, 3 likely pathogenic, 2 likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
21746	NM_138477.4(CDAN1):c.156C>G (p.Phe52Leu)	CDAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21748	NM_138477.4(CDAN1):c.2140C>T (p.Arg714Trp)	CDAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3176	NM_138477.4(CDAN1):c.3124C>T (p.Arg1042Trp)	CDAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3177	NM_138477.4(CDAN1):c.3389C>T (p.Pro1130Leu)	CDAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3179	NM_138477.2(CDAN1):c.2015C>T (p.Pro672Leu)	CDAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3180	NM_138477.4(CDAN1):c.2602T>A (p.Phe868Ile)	CDAN1	Pathogenic	no assertion criteria provided
3182	NM_138477.4(CDAN1):c.1117_1119del (p.Val373del)	CDAN1	Pathogenic	no assertion criteria provided
3178	NM_138477.4(CDAN1):c.1796A>G (p.Asn599Ser)	CDAN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3336216	NM_138477.4(CDAN1):c.152C>T (p.Pro51Leu)	CDAN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
807554	NM_138477.4(CDAN1):c.2066C>A (p.Ala689Glu)	CDAN1	Likely pathogenic	criteria provided, single submitter
262373	NM_138477.4(CDAN1):c.2872C>T (p.Leu958=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315919	NM_138477.4(CDAN1):c.3559-11A>G	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315920	NM_138477.4(CDAN1):c.3384G>A (p.Pro1128=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315921	NM_138477.4(CDAN1):c.3204+5G>A	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315927	NM_138477.4(CDAN1):c.2868C>T (p.Ala956=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315928	NM_138477.4(CDAN1):c.2805-11T>A	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315935	NM_138477.4(CDAN1):c.2406C>T (p.Ile802=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315936	NM_138477.4(CDAN1):c.2361G>A (p.Ala787=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315939	NM_138477.4(CDAN1):c.2016G>A (p.Pro672=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315940	NM_138477.4(CDAN1):c.2008-8C>T	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315944	NM_138477.4(CDAN1):c.1839G>A (p.Gly613=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315950	NM_138477.4(CDAN1):c.1058-11T>G	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315953	NM_138477.4(CDAN1):c.256C>T (p.Pro86Ser)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315957	NM_138477.4(CDAN1):c.57G>C (p.Val19=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
315959	NM_138477.4(CDAN1):c.-14G>A	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
632233	NM_138477.4(CDAN1):c.2173C>T (p.Arg725Trp)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
726722	NM_138477.4(CDAN1):c.2542-4C>G	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
747338	NM_138477.4(CDAN1):c.1368-6C>T	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
749588	NM_138477.4(CDAN1):c.2947+9C>A	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
750583	NM_138477.4(CDAN1):c.3135C>T (p.Asp1045=)	CDAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
CDIN1	Strong	Autosomal recessive	congenital dyserythropoietic anemia type type 1B	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDAN1	Orphanet:98869	Congenital dyserythropoietic anemia type I
CDIN1	Orphanet:98869	Congenital dyserythropoietic anemia type I

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDAN1	HGNC:1713	ENSG00000140326	Q8IWY9	Codanin-1	gencc,clinvar
CDIN1	HGNC:26929	ENSG00000186073	Q9Y2V0	CDAN1-interacting nuclease 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDAN1	Codanin-1	May act as a negative regulator of ASF1 in chromatin assembly.
CDIN1	CDAN1-interacting nuclease 1	Plays a role in erythroid cell differentiation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDAN1	Other/Unknown	no		Codanin-1_C, Codanin-1
CDIN1	Other/Unknown	no		CDIN1

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
sural nerve	1
ventricular zone	1
cardiac ventricle	1
heart right ventricle	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDAN1	230	ubiquitous	marker	ventricular zone, sural nerve, left ovary
CDIN1	226	ubiquitous	yes	left ventricle myocardium, heart right ventricle, cardiac ventricle

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDIN1	1,517
CDAN1	1,056

Intra-cohort edges

A	B	Sources
CDAN1	CDIN1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDAN1	Q8IWY9	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDIN1	Q9Y2V0	93.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
import into nucleus	1	1203.7×	0.003	CDAN1
erythrocyte differentiation	1	133.8×	0.015	CDIN1
intracellular protein localization	1	52.3×	0.020	CDAN1
chromatin organization	1	49.6×	0.020	CDAN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDAN1	0	0
CDIN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CDAN1, CDIN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDAN1	0	—
CDIN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01795794	PHASE4	UNKNOWN	Evaluation of the Efficacy in Decreasing Iron Absorption in Patients With Congenital Dyserythropoietic Anemia Type I by Treatment With LOSEC

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ESOMEPRAZOLE	4	1
OMEPRAZOLE	4	1