Congenital anemia

Summary

Congenital anemia (MONDO:0000577) is a disease (an umbrella term covering 8 Mondo subtypes) with 3 cohort genes and 1 clinical trial.

At a glance

• Umbrella term: 8 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 4
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital anemia
Mondo ID	MONDO:0000577
NCIT	C35228
SNOMED CT	63565007
UMLS	C0158995
MedGen	102361
GARD	0022807
Is cancer (heuristic)	no

Also known as: congenital anaemia (disease) · congenital anemia · congenital anemia (disease)

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 8 Mondo subtypes.

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

Related subtypes (18): neonatal anemia, microcytic anemia, hypochromic anemia, pancytopenia, deficiency anemia, pure red-cell aplasia, macrocytic anemia, normocytic anemia, sideroblastic anemia, aplastic anemia, hemoglobin C disease, hemoglobin E disease, beta-thalassemia and related diseases, hemoglobinopathy Toms River, hereditary methemoglobinemia, hemoglobin D disease, anemia due to enzyme disorder, anemia due to chronic disorder

Subtypes (8): 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, 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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1511	NM_000298.6(PKLR):c.1529G>A (p.Arg510Gln)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
618827	NM_000298.6(PKLR):c.994G>A (p.Gly332Ser)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
15125	NM_000518.4(HBB):c.224G>T (p.Gly75Val)	HBB	Uncertain significance	criteria provided, single submitter
315943	NM_138477.4(CDAN1):c.1967C>G (p.Thr656Ser)	CDAN1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 31 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDAN1	Orphanet:98869	Congenital dyserythropoietic anemia type I
HBB	Orphanet:2132	Hemoglobin C disease
HBB	Orphanet:2133	Hemoglobin E disease
HBB	Orphanet:231214	Beta-thalassemia major
HBB	Orphanet:231222	Beta-thalassemia intermedia
HBB	Orphanet:231226	Unstable beta globin chain variant disease
HBB	Orphanet:231237	Delta-beta-thalassemia
HBB	Orphanet:231242	Hemoglobin C-beta-thalassemia syndrome
HBB	Orphanet:231249	Hemoglobin E-beta-thalassemia syndrome
HBB	Orphanet:232	Sickle cell anemia
HBB	Orphanet:247511	Autosomal dominant secondary polycythemia
HBB	Orphanet:251365	Sickle cell S-C disease
HBB	Orphanet:251370	Sickle cell S-D Punjab disease
HBB	Orphanet:251375	Sickle cell S-E disease
HBB	Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
HBB	Orphanet:330041	Hemoglobin M disease
HBB	Orphanet:46532	Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
HBB	Orphanet:695140	Sickle cell-beta zero-thalassemia
HBB	Orphanet:695147	Sickle cell-beta plus-thalassemia
HBB	Orphanet:699822	Sickle cell S-Lepore disease
HBB	Orphanet:700090	Sickle cell S-O Arab disease
HBB	Orphanet:700107	Sickle cell S-other specified hemoglobin variant
HBB	Orphanet:700111	Homozygous hemoglobin O Arab disease
HBB	Orphanet:715125	Hemoglobin E-beta-thalassemia intermedia
HBB	Orphanet:715128	Hemoglobin E-beta-thalassemia major
HBB	Orphanet:715135	Hemoglobin Lepore-beta-thalassemia intermedia
HBB	Orphanet:715140	Hemoglobin Lepore-beta-thalassemia major
HBB	Orphanet:715143	Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBB	Orphanet:715157	Low oxygen affinity beta chain hemoglobin disease
HBB	Orphanet:90039	Hemoglobin D disease
PKLR	Orphanet:766	Hemolytic anemia due to red cell pyruvate kinase deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDAN1	HGNC:1713	ENSG00000140326	Q8IWY9	Codanin-1	clinvar
HBB	HGNC:4827	ENSG00000244734	P68871	Hemoglobin subunit beta	clinvar
PKLR	HGNC:9020	ENSG00000143627	P30613	Pyruvate kinase PKLR	clinvar

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.
HBB	Hemoglobin subunit beta	Involved in oxygen transport from the lung to the various peripheral tissues.
PKLR	Pyruvate kinase PKLR	Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDAN1	Other/Unknown	no		Codanin-1_C, Codanin-1
HBB	Other/Unknown	no		Globin, Hemoglobin_b, Globin-like_sf
PKLR	Kinase	yes	2.7.1.40	Pyr_Knase, Pyrv_Knase-like_insert_dom_sf, Pyrv_Knase_brl

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
sural nerve	1
ventricular zone	1
monocyte	1
trabecular bone tissue	1
vena cava	1
duodenum	1
liver	1
right lobe of liver	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
HBB	284	broad	marker	monocyte, trabecular bone tissue, vena cava
PKLR	69	tissue_specific	marker	liver, right lobe of liver, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDAN1	1,056
HBB	454
PKLR	94

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HBB	P68871	350
PKLR	P30613	58
CDAN1	Q8IWY9	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 3 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
Heme assimilation	1	1903.3×	0.007	HBB
Erythrocytes take up oxygen and release carbon dioxide	1	634.4×	0.007	HBB
ChREBP activates metabolic gene expression	1	634.4×	0.007	PKLR
Erythrocytes take up carbon dioxide and release oxygen	1	439.2×	0.007	HBB
Scavenging of heme from plasma	1	439.2×	0.007	HBB
Regulation of gene expression in beta cells	1	259.6×	0.009	PKLR
Chaperone Mediated Autophagy	1	248.3×	0.009	HBB
Pyruvate metabolism	1	203.9×	0.009	PKLR
Late endosomal microautophagy	1	163.1×	0.010	HBB
Glycolysis	1	142.8×	0.010	PKLR
Heme signaling	1	107.7×	0.013	HBB
Cytoprotection by HMOX1	1	92.1×	0.013	HBB
SARS-CoV-1-host interactions	1	87.8×	0.013	PKLR
Factors involved in megakaryocyte development and platelet production	1	33.2×	0.032	HBB
Neutrophil degranulation	1	11.5×	0.085	HBB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nitric oxide transport	1	1123.5×	0.008	HBB
import into nucleus	1	802.5×	0.008	CDAN1
pyruvate biosynthetic process	1	702.2×	0.008	PKLR
cellular oxidant detoxification	1	624.1×	0.008	HBB
renal absorption	1	561.7×	0.008	HBB
response to metal ion	1	510.7×	0.008	PKLR
carbon dioxide transport	1	432.1×	0.008	HBB
cellular response to epinephrine stimulus	1	432.1×	0.008	PKLR
oxygen transport	1	351.1×	0.008	HBB
response to ATP	1	330.4×	0.008	PKLR
hydrogen peroxide catabolic process	1	224.7×	0.010	HBB
blood vessel diameter maintenance	1	208.1×	0.010	HBB
erythrocyte development	1	175.5×	0.011	HBB
response to cAMP	1	170.2×	0.011	PKLR
response to hydrogen peroxide	1	156.0×	0.011	HBB
positive regulation of nitric oxide biosynthetic process	1	151.8×	0.011	HBB
glycolytic process	1	127.7×	0.012	PKLR
platelet aggregation	1	112.3×	0.013	HBB
response to nutrient	1	98.5×	0.014	PKLR
response to glucose	1	85.1×	0.015	PKLR
regulation of blood pressure	1	73.9×	0.017	HBB
cellular response to insulin stimulus	1	56.7×	0.021	PKLR
intracellular protein localization	1	34.9×	0.032	CDAN1
chromatin organization	1	33.0×	0.032	CDAN1
response to hypoxia	1	31.9×	0.032	PKLR
inflammatory response	1	12.6×	0.077	HBB

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
HBB	CANDESARTAN CILEXETIL
PKLR	MITAPIVAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HBB	23	4
PKLR	3	4
CDAN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANDESARTAN CILEXETIL	4	HBB
MECHLORETHAMINE HYDROCHLORIDE	4	HBB
PHENAZOPYRIDINE HYDROCHLORIDE	4	HBB
MERCAPTOPURINE ANHYDROUS	4	HBB
AZACITIDINE	4	HBB
AZATHIOPRINE	4	HBB
TOPOTECAN HYDROCHLORIDE	4	HBB
ACYCLOVIR	4	HBB
FLUOROURACIL	4	HBB
RAUWOLFIA SERPENTINA	4	HBB
HYDROQUINONE	4	HBB
MENADIONE	4	HBB
THIOTEPA	4	HBB
THIOGUANINE	4	HBB
RESERPINE	4	HBB
MITAPIVAT	4	PKLR
CURCUMIN	3	HBB
HYDROXYCAMPTOTHECIN	3	HBB
SURAMIN	3	PKLR
MOLIBRESIB	2	HBB
FISETIN	2	HBB
TEROXIRONE	2	HBB
5-FLUOROURIDINE	2	HBB
ELLAGIC ACID	2	HBB, PKLR
BAICALEIN	2	HBB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PKLR	82	Binding:69, Functional:12, ADMET:1
HBB	68	Binding:50, Functional:18

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PKLR	2.7.1.40	pyruvate kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

25 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)
CANDESARTAN CILEXETIL	4	HBB
MECHLORETHAMINE HYDROCHLORIDE	4	HBB
PHENAZOPYRIDINE HYDROCHLORIDE	4	HBB
MERCAPTOPURINE ANHYDROUS	4	HBB
AZACITIDINE	4	HBB
AZATHIOPRINE	4	HBB
TOPOTECAN HYDROCHLORIDE	4	HBB
ACYCLOVIR	4	HBB
FLUOROURACIL	4	HBB
RAUWOLFIA SERPENTINA	4	HBB
HYDROQUINONE	4	HBB
MENADIONE	4	HBB
THIOTEPA	4	HBB
THIOGUANINE	4	HBB
RESERPINE	4	HBB
MITAPIVAT	4	PKLR
CURCUMIN	3	HBB
HYDROXYCAMPTOTHECIN	3	HBB
SURAMIN	3	PKLR
MOLIBRESIB	2	HBB
FISETIN	2	HBB
TEROXIRONE	2	HBB
5-FLUOROURIDINE	2	HBB
ELLAGIC ACID	2	HBB, PKLR
BAICALEIN	2	HBB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	HBB, PKLR
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	1	CDAN1

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)
CDAN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00658385	Not specified	COMPLETED	Assess the Feasibility and Safety of Granulocyte Colony Stimulating Factor (GCSF) Mobilization of CD34+ Hematopoietic Progenitor Cells in Patients With Betathalassemia Major