Congenital nonspherocytic hemolytic anemia

Summary

Congenital nonspherocytic hemolytic anemia (MONDO:0006506) is a disease (an umbrella term covering 10 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 10 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital nonspherocytic hemolytic anemia
Mondo ID	MONDO:0006506
EFO	EFO:1000641
MeSH	D000746
OMIM	300908
DOID	DOID:2861
SNOMED CT	301317008
UMLS	C0002882
MedGen	284
GARD	0024433
Is cancer (heuristic)	no

Also known as: anemia, congenital, nonspherocytic hemolytic

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 10 Mondo subtypes.

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

Related subtypes (7): myopathy, lactic acidosis, and sideroblastic 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

Subtypes (10): anemia, nonspherocytic hemolytic, gamma-glutamylcysteine synthetase deficiency, glutathione synthetase deficiency without 5-oxoprolinuria, non-spherocytic hemolytic anemia due to hexokinase deficiency, hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency, pyruvate kinase deficiency of red cells, hemolytic anemia due to adenylate kinase deficiency, hemolytic anemia due to glucophosphate isomerase deficiency, hemolytic anemia due to glutathione reductase deficiency, hemolytic anemia due to erythrocyte adenosine deaminase overproduction

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 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10401	NM_000402.4(G6PD):c.1039G>A (p.Glu347Lys)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
G6PD	Orphanet:466026	Class I glucose-6-phosphate dehydrogenase deficiency

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
G6PD	HGNC:4057	ENSG00000160211	P11413	Glucose-6-phosphate 1-dehydrogenase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
G6PD	Glucose-6-phosphate 1-dehydrogenase	Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
G6PD	Enzyme (other)	yes	1.1.1.49	G6P_DH, G6P_DH_AS, G6P_DH_NAD-bd

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
granulocyte	1
right testis	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
G6PD	218	ubiquitous	marker	stromal cell of endometrium, granulocyte, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
G6PD	4,226

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
G6PD	P11413	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
NFE2L2 regulates pentose phosphate pathway genes	1	1427.5×	0.002	G6PD
Pentose phosphate pathway	1	951.7×	0.002	G6PD
TP53 Regulates Metabolic Genes	1	129.8×	0.008	G6PD

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
ribose phosphate biosynthetic process	1	16852.0×	6e-04	G6PD
response to iron(III) ion	1	8426.0×	6e-04	G6PD
pentose biosynthetic process	1	8426.0×	6e-04	G6PD
positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	8426.0×	6e-04	G6PD
pentose-phosphate shunt, oxidative branch	1	4213.0×	9e-04	G6PD
pentose-phosphate shunt	1	1532.0×	0.002	G6PD
NADP+ metabolic process	1	1532.0×	0.002	G6PD
negative regulation of cell growth involved in cardiac muscle cell development	1	1404.3×	0.002	G6PD
glucose 6-phosphate metabolic process	1	1296.3×	0.002	G6PD
negative regulation of reactive oxygen species metabolic process	1	936.2×	0.002	G6PD
erythrocyte maturation	1	842.6×	0.002	G6PD
regulation of neuron apoptotic process	1	702.2×	0.002	G6PD
response to food	1	495.6×	0.003	G6PD
cholesterol biosynthetic process	1	421.3×	0.003	G6PD
substantia nigra development	1	366.4×	0.004	G6PD
glutathione metabolic process	1	351.1×	0.004	G6PD
glucose metabolic process	1	255.3×	0.005	G6PD
cellular response to oxidative stress	1	154.6×	0.007	G6PD
response to ethanol	1	146.5×	0.007	G6PD
lipid metabolic process	1	91.6×	0.011	G6PD

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

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
G6PD	BREXANOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
G6PD	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
G6PD	49	Binding:46, ADMET:2, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
G6PD	1.1.1.49	glucose-6-phosphate dehydrogenase (NADP+)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
G6PD	1

Chemical tractability of cohort targets

8 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)
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	G6PD
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	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.