Hemolytic anemia due to diphosphoglycerate mutase deficiency

Summary

Hemolytic anemia due to diphosphoglycerate mutase deficiency (MONDO:0009113) is a disease caused by BPGM (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BPGM (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemolytic anemia due to diphosphoglycerate mutase deficiency
Mondo ID	MONDO:0009113
OMIM	222800
Orphanet	714
DOID	DOID:0111630
NCIT	C131638
UMLS	C1291620
MedGen	489898
GARD	0001874
Is cancer (heuristic)	no

Also known as: diphosphoglycerate phosphatase deficiency · erythrocytosis, familial, 8

Data availability: 8 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › hemolytic anemia due to diphosphoglycerate mutase deficiency

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, 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, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
12091	NM_001724.5(BPGM):c.268C>T (p.Arg90Cys)	BPGM	Pathogenic	criteria provided, single submitter
12092	NM_001724.5(BPGM):c.61del (p.Arg21fs)	BPGM	Pathogenic	no assertion criteria provided
973177	NM_001724.5(BPGM):c.185G>A (p.Arg62Gln)	BPGM	Pathogenic	no assertion criteria provided
973178	NM_001724.5(BPGM):c.269G>A (p.Arg90His)	BPGM	Pathogenic	no assertion criteria provided
2704279	NM_001724.5(BPGM):c.679C>T (p.Arg227Cys)	BPGM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2439542	NM_001724.5(BPGM):c.461G>A (p.Arg154Gln)	BPGM	Uncertain significance	criteria provided, single submitter
2920936	NM_001724.5(BPGM):c.62G>A (p.Arg21His)	BPGM	Uncertain significance	criteria provided, single submitter
4685693	NM_001724.5(BPGM):c.601+16A>G	BPGM	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
BPGM	Strong	Autosomal recessive	hemolytic anemia due to diphosphoglycerate mutase deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BPGM	Orphanet:247378	Autosomal recessive secondary polycythemia not associated with VHL gene
BPGM	Orphanet:714	Hemolytic anemia due to diphosphoglycerate mutase 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
BPGM	HGNC:1093	ENSG00000172331	P07738	Bisphosphoglycerate mutase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BPGM	Bisphosphoglycerate mutase	Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG).

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)
BPGM	Enzyme (other)	yes	5.4.2.4	PG/BPGM_mutase_AS, Phosphogly_mut1, His_Pase_superF_clade-1

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
amniotic fluid	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BPGM	283	ubiquitous	marker	secondary oocyte, oocyte, amniotic fluid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BPGM	1,881

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BPGM	P07738	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Glycolysis	1	285.5×	0.004	BPGM

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
carbohydrate derivative catabolic process	1	16852.0×	6e-04	BPGM
neuroinflammatory response	1	1532.0×	0.002	BPGM
establishment of blood-brain barrier	1	1404.3×	0.002	BPGM
oxygen transport	1	1053.2×	0.002	BPGM
cellular response to stress	1	842.6×	0.002	BPGM
respiratory gaseous exchange by respiratory system	1	624.1×	0.002	BPGM
defense response to protozoan	1	601.9×	0.002	BPGM
erythrocyte development	1	526.6×	0.002	BPGM
glycolytic process	1	383.0×	0.003	BPGM
carbohydrate metabolic process	1	135.9×	0.007	BPGM

Therapeutics

Drug target analysis

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

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
BPGM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BPGM	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BPGM	5.4.2.4	Bisphosphoglycerate mutase

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

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	1	BPGM
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
BPGM	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.