BPGM

protein-coding

bisphosphoglycerate mutase, the group of Phosphoglycerate mutases|Bisphosphoglycerate phosphatases

Gene summary

2,3-diphosphoglycerate (2,3-DPG) is a small molecule found at high concentrations in red blood cells where it binds to and decreases the oxygen affinity of hemoglobin. This gene encodes a multifunctional enzyme that catalyzes 2,3-DPG synthesis via its synthetase activity, and 2,3-DPG degradation via its phosphatase activity. The enzyme also has phosphoglycerate phosphomutase activity. Deficiency of this enzyme increases the affinity of cells for oxygen. Mutations in this gene result in hemolytic anemia. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MANE transcript

NM_001724.5

Inheritance

AR, AD

ClinVar variants

P:4U:37B:14

Top phenotype

Erythrocytosis, familial, 8

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr7:134,646,811-134,679,816

External References & Databases

Ensembl (ENSG00000172331)

Transcript & Mutation Effects

hg38 • Region Span ~33.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hemolytic anemia due to diphosphoglycerate mutase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009113

Submitter: Labcorp Genetics (formerly Invitae)

hemolytic anemia due to diphosphoglycerate mutase deficiencyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0009113

Submitter: PanelApp Australia

hemolytic anemia due to diphosphoglycerate mutase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009113

Submitter: Ambry Genetics

hemolytic anemia due to diphosphoglycerate mutase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009113

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Erythrocytosis, familial, 8AD/AR

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Phlebotomy has been reported as beneficial in individuals with recessive disease involving severe loss of enzymatic function; Other reports indicate that RBC transfusions and splenectomy may be indicated in some individuals

Refs: 14131784; 5885535; 11947623; 152321; 2542247; 1421379

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BPGM variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 19

Deficiency of bisphosphoglycerate mutaseTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001724.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	12 clinvar		14
missense	3 clinvar		34 clinvar	2 clinvar		39
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	0	37	14	0	55

Highest pathogenic variant AF is 0.000010533412

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001724.5	RefSeq	NP_001715.1	2	MANE Select
ENST00000344924.8	Ensembl	ENSP00000342032.3	2	MANE Select
NM_001293085.2	RefSeq	NP_001280014.1	2	Standard
NM_199186.3	RefSeq	NP_954655.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycolysis / Gluconeogenesis - Homo sapiens (human)
Glycine, serine and threonine metabolism - Homo sapiens (human)
Glycolysis
Glycogenosis, Type VII. Tarui disease
Gluconeogenesis

Biological Process

carbohydrate metabolic process
respiratory gaseous exchange
erythrocyte development
canonical glycolysis

Molecular Function

bisphosphoglycerate mutase activity
phosphoglycerate mutase activity
hydrolase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393132
Coding exons: 2
Length: 33006
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125747
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.703	125	149	0.838	0.00000860	1704
Missense (PolyPhen)		41	57.13	0.71767		693
Synonymous	0.732	49	56.0	0.876	0.00000319	498
Loss of Function	1.58	4	9.14	0.438	3.88e-7	113

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3- bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.11) activity. {ECO:0000269|PubMed:21045285}.;
Disease: DISEASE: Bisphosphoglycerate mutase deficiency (BPGMD) [MIM:222800]: A disease characterized by hemolytic anemia, splenomegaly, cholelithiasis and cholecystitis. {ECO:0000269|PubMed:1421379, ECO:0000269|PubMed:15054810, ECO:0000269|PubMed:2542247}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.186

Intolerance Scores

LoFtool: 0.576
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.946

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium