BPGM

bisphosphoglycerate mutase, the group of Phosphoglycerate mutases|Bisphosphoglycerate phosphatases

Basic information

Region (hg38): 7:134646811-134679816

Links

ENSG00000172331 ∙ NCBI:669 ∙ OMIM:613896 ∙ HGNC:1093 ∙ Uniprot:P07738 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemolytic anemia due to diphosphoglycerate mutase deficiency (Moderate), mode of inheritance: AR
• hemolytic anemia due to diphosphoglycerate mutase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Erythrocytosis, familial, 8	AD/AR	Hematologic	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	Hematologic	14131784; 5885535; 11947623; 152321; 2542247; 1421379

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BPGM gene.

• not provided (1 variants)
• Deficiency of bisphosphoglycerate mutase (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BPGM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6		6
missense	1		14	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	14	7	0

Variants in BPGM

This is a list of pathogenic ClinVar variants found in the BPGM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-134661566-AC-A		Deficiency of bisphosphoglycerate mutase	Pathogenic (Nov 15, 1992)
7-134661569-G-A		Deficiency of bisphosphoglycerate mutase	Uncertain significance (May 26, 2023)
7-134661689-A-C			Uncertain significance (Sep 25, 2021)
7-134661692-G-A		Deficiency of bisphosphoglycerate mutase	Pathogenic (Jul 17, 2020)
7-134661693-G-A			Likely benign (Apr 06, 2023)
7-134661754-A-T		not specified	Uncertain significance (Sep 12, 2023)
7-134661775-C-T		Deficiency of bisphosphoglycerate mutase	Pathogenic (Apr 12, 2023)
7-134661776-G-A		Deficiency of bisphosphoglycerate mutase	Pathogenic (Nov 15, 1992)
7-134661796-G-C		not specified	Uncertain significance (Nov 17, 2022)
7-134661820-T-G			Uncertain significance (Jun 18, 2022)
7-134661876-G-A			Likely benign (Aug 19, 2022)
7-134661895-C-T		not specified	Uncertain significance (Oct 12, 2022)
7-134661926-G-A		not specified	Uncertain significance (Aug 14, 2023)
7-134661942-C-T			Likely benign (Jul 17, 2022)
7-134661960-A-C		not specified	Uncertain significance (Feb 21, 2024)
7-134661968-G-A		Deficiency of bisphosphoglycerate mutase	Uncertain significance (Mar 16, 2022)
7-134661968-G-T		not specified	Uncertain significance (May 29, 2024)
7-134661993-G-A			Likely benign (Sep 27, 2023)
7-134662000-C-T		not specified	Uncertain significance (Dec 02, 2022)
7-134662019-A-G		not specified	Uncertain significance (Sep 01, 2021)
7-134662022-G-T		not specified	Uncertain significance (Jul 19, 2023)
7-134662033-G-A		not specified	Uncertain significance (Feb 21, 2024)
7-134662053-C-T			Likely benign (Sep 09, 2022)
7-134662082-G-A		not specified	Uncertain significance (Sep 26, 2023)
7-134662101-C-A		not specified	Uncertain significance (Apr 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BPGM	protein_coding	protein_coding	ENST00000393132	2	33006

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0213	0.914	125723	0	24	125747	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.703	125	149	0.838	0.00000860	1704
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Glycine, serine and threonine metabolism - Homo sapiens (human);Glycolysis;Glycogenosis, Type VII. Tarui disease;Gluconeogenesis;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Fanconi-bickel syndrome;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Metabolism of carbohydrates;Glycolysis Gluconeogenesis;Metabolism;Rapoport-Luebering glycolytic shunt;Glycolysis;gluconeogenesis;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.576
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.719
• hipred: Y
• hipred_score: 0.804
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.946

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bpgm

Gene ontology

• Biological process: carbohydrate metabolic process;respiratory gaseous exchange;erythrocyte development;canonical glycolysis
• Cellular component: cytosol;extracellular exosome
• Molecular function: bisphosphoglycerate mutase activity;phosphoglycerate mutase activity;hydrolase activity