Congenital dyserythropoietic anemia type 3

Summary

Congenital dyserythropoietic anemia type 3 (MONDO:0007109) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 7
• Phenotypes (HPO): 20

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		60	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0001903	Anemia	Very frequent (80-99%)
HP:0004447	Poikilocytosis	Very frequent (80-99%)
HP:0011273	Anisocytosis	Very frequent (80-99%)
HP:0002904	Hyperbilirubinemia	Frequent (30-79%)
HP:0003452	Increased serum iron	Frequent (30-79%)
HP:0005518	Increased mean corpuscular volume	Frequent (30-79%)
HP:0012130	Abnormality of cells of the erythroid lineage	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0025035	Abnormal proerythroblast morphology	Frequent (30-79%)
HP:0025196	Increased total iron binding capacity	Frequent (30-79%)
HP:0025354	Abnormal cellular phenotype	Frequent (30-79%)
HP:0001877	Abnormal erythrocyte morphology	Occasional (5-29%)
HP:0000225	Gingival bleeding	Occasional (5-29%)
HP:0000980	Pallor	Occasional (5-29%)
HP:0002249	Melena	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0011891	Post-partum hemorrhage	Occasional (5-29%)
HP:0030140	Oral cavity bleeding	Occasional (5-29%)
HP:0004322	Short stature	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital dyserythropoietic anemia type 3
Mondo ID	MONDO:0007109
OMIM	105600
Orphanet	98870
DOID	DOID:0111399
SNOMED CT	26409005
UMLS	C5676874
MedGen	1801596
GARD	0002002
Is cancer (heuristic)	no

Also known as: anaemia with multinucleated erythroblasts · anemia, congenital dyserythropoietic, type III · CDA III · CDA type 3 · CDA type III · CDAN3 · congenital dyserythropoietic anemia type 3 · dyserythropoietic anemia, congenital type 3 · dyserythropoietic anemia, congenital, type III

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › congenital dyserythropoietic anemia type 3

Related subtypes (7): myopathy, lactic acidosis, and sideroblastic anemia, congenital nonspherocytic hemolytic anemia, congenital dyserythropoietic anemia type 2, congenital dyserythropoietic anemia type 4, severe congenital hypochromic anemia with ringed sideroblasts, Fanconi anemia, congenital dyserythropoietic anemia type 1

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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344522	NM_001367805.3(KIF23):c.2875del (p.Leu959fs)	KIF23	Pathogenic	no assertion criteria provided
1344521	NM_001367805.3(KIF23):c.2789C>G (p.Pro930Arg)	KIF23	Likely pathogenic	criteria provided, single submitter
4278021	NM_001367805.3(KIF23):c.2866G>A (p.Gly956Arg)	KIF23	Likely pathogenic	criteria provided, single submitter
2582639	NM_001367805.3(KIF23):c.2482T>A (p.Ser828Thr)	KIF23	Uncertain significance	criteria provided, single submitter
2597070	NM_001367805.3(KIF23):c.1508A>G (p.Asn503Ser)	KIF23	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064722	NM_001367805.3(KIF23):c.1324A>G (p.Arg442Gly)	KIF23	Uncertain significance	criteria provided, single submitter
4277740	NM_001367805.3(KIF23):c.518G>A (p.Arg173His)	KIF23	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
KIF23	Moderate	Autosomal dominant	congenital dyserythropoietic anemia type 3	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF23	Orphanet:98870	Congenital dyserythropoietic anemia type III

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
KIF23	HGNC:6392	ENSG00000137807	Q02241	Kinesin-like protein KIF23	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF23	Kinesin-like protein KIF23	Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis.

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)
KIF23	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

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
ganglionic eminence	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF23	201	ubiquitous	marker	ventricular zone, secondary oocyte, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF23	5,382

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF23	Q02241	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Mitotic Telophase/Cytokinesis	1	1427.5×	0.011	KIF23
Kinesins	1	178.4×	0.028	KIF23
Golgi-to-ER retrograde transport	1	132.8×	0.028	KIF23
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.028	KIF23
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.028	KIF23
MHC class II antigen presentation	1	89.2×	0.028	KIF23
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.028	KIF23
M Phase	1	66.0×	0.028	KIF23
Cell Cycle, Mitotic	1	48.2×	0.033	KIF23
Membrane Trafficking	1	37.1×	0.033	KIF23
Hemostasis	1	36.0×	0.033	KIF23
Cell Cycle	1	36.0×	0.033	KIF23
Vesicle-mediated transport	1	34.8×	0.033	KIF23
Adaptive Immune System	1	29.8×	0.036	KIF23
Immune System	1	13.0×	0.077	KIF23

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
mitotic spindle elongation	1	8426.0×	6e-04	KIF23
mitotic spindle midzone assembly	1	1532.0×	0.002	KIF23
positive regulation of cytokinesis	1	401.2×	0.004	KIF23
microtubule-based movement	1	295.6×	0.004	KIF23
mitotic cytokinesis	1	259.3×	0.004	KIF23

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
KIF23	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AZD-4877	2	KIF23

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KIF23	15	Binding:15

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)
AZD-4877	2	KIF23

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	KIF23
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: 0.