PGAM2

phosphoglycerate mutase 2, the group of Phosphoglycerate mutases|Bisphosphoglycerate phosphatases

Basic information

Region (hg38): 7:44062727-44065567

Links

ENSG00000164708 ∙ NCBI:5224 ∙ OMIM:612931 ∙ HGNC:8889 ∙ Uniprot:P15259 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to phosphoglycerate mutase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to phosphoglycerate mutase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to phosphoglycerate mutase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease X	AR	Renal	Preventive measures to reduce the chance of severe sequelae can be beneficial, as individuals can present with exercise intolerance, and renal failure has been described	Biochemical; Musculoskeletal; Renal	6283419; 6262916; 6308514; 8447317; 10545043; 19273759

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGAM2 gene.

• Glycogen storage disease type X (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGAM2 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			2	33	2	37
missense			81		1	82
nonsense	4	1				5
start loss						0
frameshift	2	2				4
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			4	4		8
non coding			1	9	1	11
Total	6	3	86	42	4

Highest pathogenic variant AF is 0.0000133

Variants in PGAM2

This is a list of pathogenic ClinVar variants found in the PGAM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-44062729-T-C		Glycogen storage disease type X	Uncertain significance (Jan 12, 2018)
7-44062771-G-T		Glycogen storage disease type X	Uncertain significance (Jun 27, 2023)
7-44062800-G-A		Glycogen storage disease type X • PGAM2-related disorder	Conflicting classifications of pathogenicity (Jan 23, 2025)
7-44062806-C-G		Glycogen storage disease type X	Likely benign (Dec 24, 2021)
7-44062807-C-T		Glycogen storage disease type X • Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
7-44062808-G-C		Inborn genetic diseases	Uncertain significance (Nov 04, 2022)
7-44062812-C-T		Glycogen storage disease type X	Likely benign (Jul 31, 2024)
7-44062813-G-A		Glycogen storage disease type X • Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
7-44062819-T-G		Glycogen storage disease type X • PGAM2-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2025)
7-44062842-C-T		Glycogen storage disease type X	Likely benign (Oct 31, 2022)
7-44062853-T-G		Glycogen storage disease type X • Inborn genetic diseases	Uncertain significance (May 23, 2023)
7-44062882-G-T		Inborn genetic diseases	Uncertain significance (Mar 05, 2024)
7-44062889-C-T		Rhabdomyolysis	Likely pathogenic (Aug 05, 2017)
7-44062890-C-T		Glycogen storage disease type X	Likely benign (Mar 19, 2024)
7-44062891-G-A			Uncertain significance (Sep 15, 2023)
7-44062915-G-A		Glycogen storage disease type X	Uncertain significance (Sep 01, 2021)
7-44062933-A-G		Glycogen storage disease type X	Benign/Likely benign (Jan 20, 2025)
7-44062937-C-T		Glycogen storage disease type X	Uncertain significance (Apr 05, 2023)
7-44062938-G-A		Glycogen storage disease type X	Likely benign (Feb 02, 2024)
7-44062947-A-G		Glycogen storage disease type X	Likely benign (Oct 01, 2022)
7-44064620-A-G			Benign (Jun 29, 2018)
7-44064815-C-T		Glycogen storage disease type X	Likely benign (Feb 06, 2023)
7-44064821-G-A		Glycogen storage disease type X	Likely benign (Jun 22, 2024)
7-44064829-C-A		Glycogen storage disease type X	Uncertain significance (Aug 22, 2022)
7-44064832-C-A		Glycogen storage disease type X	Uncertain significance (Jul 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGAM2	protein_coding	protein_coding	ENST00000297283	3	2861

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.36e-7	0.118	125574	1	172	125747	0.000688

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.667	180	157	1.15	0.0000105	1647
Missense in Polyphen		78	68.633	1.1365		705
Synonymous	-0.651	70	63.4	1.10	0.00000432	500
Loss of Function	-0.287	10	9.07	1.10	3.97e-7	106

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00789	0.00785
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000204	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.000294	0.000294
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Interconversion of 3- and 2-phosphoglycerate with 2,3- bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase), but with a reduced activity.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Glycine, serine and threonine metabolism - Homo sapiens (human);Warburg Effect;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;Glycolysis and Gluconeogenesis;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;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.468
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.56

Haploinsufficiency Scores

• pHI: 0.703
• hipred: Y
• hipred_score: 0.665
• ghis: 0.445

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pgam2

Zebrafish Information Network

• Gene name: pgam2
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased diameter

Gene ontology

• Biological process: gluconeogenesis;glycolytic process;striated muscle contraction;Notch signaling pathway;spermatogenesis;response to mercury ion;canonical glycolysis
• Cellular component: nucleus;cytosol;extracellular exosome
• Molecular function: bisphosphoglycerate mutase activity;phosphoglycerate mutase activity;hydrolase activity;2,3-bisphosphoglycerate-dependent phosphoglycerate mutase activity;cofactor binding