PGM1

phosphoglucomutase 1

Basic information

Region (hg38): 1:63593410-63660245

Links

ENSG00000079739 ∙ NCBI:5236 ∙ OMIM:171900 ∙ HGNC:8905 ∙ Uniprot:P36871 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PGM1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• PGM1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• PGM1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• PGM1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• PGM1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• PGM1-congenital disorder of glycosylation (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type It	AR	Biochemical; Cardiovascular; Hematologic; Pharmacogenomic; Renal	Treatment with galactose has been described as beneficial (including related to individuals with reported hypogonadotropic hypogonadism as well as parameters related to hepatic function); Individuals may have exercise-induced intolerance with episodic rhabdomyolysis, and precautions may decrease associated morbidity; Individuals have been described with dilated cardiomyopathy, and surveillance may allow early medical management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Hepatic-metabolized agents should be avoided; Cardiac transplant has been described	Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Renal	19625727; 22492991; 24499211; 28617415

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGM1 gene.

• PGM1-congenital disorder of glycosylation (281 variants)
• not provided (124 variants)
• not specified (45 variants)
• Congenital disorder of glycosylation (35 variants)
• Inborn genetic diseases (34 variants)
• PGM1-related condition (3 variants)
• PGM1-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGM1 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	70	1	77
missense	3	3	123	4	2	135
nonsense	4	3	1			8
start loss						0
frameshift	15					15
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region		1	10	14	1	26
non coding			15	55	44	114
Total	22	7	145	129	47

Highest pathogenic variant AF is 0.0000329

Variants in PGM1

This is a list of pathogenic ClinVar variants found in the PGM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-63593440-C-G		not specified	Likely benign (Feb 06, 2018)
1-63593448-G-A			Likely benign (May 18, 2018)
1-63593450-C-G		PGM1-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
1-63593493-T-G		PGM1-congenital disorder of glycosylation	Uncertain significance (Apr 22, 2022)
1-63593500-C-A		PGM1-congenital disorder of glycosylation	Likely benign (Jan 04, 2024)
1-63593506-A-G		PGM1-congenital disorder of glycosylation	Benign/Likely benign (Jan 15, 2024)
1-63593511-A-G		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
1-63593512-G-T		PGM1-congenital disorder of glycosylation	Uncertain significance (Aug 10, 2023)
1-63593512-GACCCAGGCGT-G		PGM1-congenital disorder of glycosylation	Pathogenic (Dec 04, 2023)
1-63593526-A-C		PGM1-congenital disorder of glycosylation	Uncertain significance (Jun 27, 2022)
1-63593530-C-T		PGM1-congenital disorder of glycosylation	Likely benign (Oct 17, 2022)
1-63593536-G-A		PGM1-congenital disorder of glycosylation	Likely benign (Sep 21, 2022)
1-63593539-G-C		PGM1-congenital disorder of glycosylation	Likely benign (Sep 19, 2023)
1-63593544-C-G		Inborn genetic diseases	Uncertain significance (Jan 17, 2023)
1-63593545-G-A		PGM1-congenital disorder of glycosylation	Likely benign (Nov 26, 2021)
1-63593548-C-T		PGM1-congenital disorder of glycosylation	Likely benign (Sep 10, 2023)
1-63593552-C-T		not specified • PGM1-congenital disorder of glycosylation	Likely benign (Oct 25, 2023)
1-63593562-G-A			Uncertain significance (Mar 01, 2019)
1-63593564-G-A		PGM1-congenital disorder of glycosylation	Uncertain significance (Dec 09, 2021)
1-63593574-TCC-T		PGM1-congenital disorder of glycosylation	Pathogenic (Dec 08, 2023)
1-63593574-TCCAGAGCA-T		PGM1-congenital disorder of glycosylation	Pathogenic (Aug 17, 2023)
1-63593578-G-A		PGM1-congenital disorder of glycosylation	Likely benign (Jun 06, 2023)
1-63593579-A-G		PGM1-congenital disorder of glycosylation	Uncertain significance (Oct 18, 2021)
1-63593585-G-C		PGM1-congenital disorder of glycosylation	Uncertain significance (Jul 17, 2022)
1-63593587-C-T		PGM1-congenital disorder of glycosylation	Likely benign (Oct 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGM1	protein_coding	protein_coding	ENST00000371083	11	66970

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.06e-15	0.0260	123485	18	2245	125748	0.00904

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.228	336	324	1.04	0.0000196	3816
Missense in Polyphen		148	143.48	1.0315		1606
Synonymous	-1.36	139	120	1.16	0.00000732	1132
Loss of Function	0.317	23	24.7	0.931	0.00000140	305

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00522	0.00496
Ashkenazi Jewish	0.0208	0.0202
East Asian	0.000728	0.000707
Finnish	0.00753	0.00733
European (Non-Finnish)	0.0154	0.0143
Middle Eastern	0.000728	0.000707
South Asian	0.00288	0.00278
Other	0.00881	0.00851

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This enzyme participates in both the breakdown and synthesis of glucose.
• Disease: DISEASE: Congenital disorder of glycosylation 1T (CDG1T) [MIM:614921]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:19625727, ECO:0000269|PubMed:22492991, ECO:0000269|PubMed:22976764, ECO:0000269|PubMed:24499211, ECO:0000269|PubMed:25288802, ECO:0000269|PubMed:26972339}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Starch and sucrose metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Galactosemia III;Galactosemia II (GALK);Glycogen synthetase deficiency;Glycogenosis, Type III. Cori disease, Debrancher glycogenosis;Mucopolysaccharidosis VI. Sly syndrome;Sucrase-isomaltase deficiency;Glycogenosis, Type IV. Amylopectinosis, Anderson disease;Glycogenosis, Type VI. Hers disease;Pentose Phosphate Pathway;Galactose Metabolism;Gluconeogenesis;Starch and Sucrose Metabolism;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Nucleotide Sugars Metabolism;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Transaldolase deficiency;Galactosemia;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Ectoderm Differentiation;Pathways in clear cell renal cell carcinoma;Glycogen Metabolism;Glucuronidation;Neutrophil degranulation;Metabolism of carbohydrates;glycogenolysis;Glycolysis Gluconeogenesis;TCR;Innate Immune System;Immune System;Metabolism;Pentose phosphate cycle;D-galactose degradation V (Leloir pathway);Galactose catabolism;GDP-glucose biosynthesis II;glycogen biosynthesis;HIF-1-alpha transcription factor network;Glycogen breakdown (glycogenolysis);Galactose metabolism;Glycogen synthesis;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.631

Intolerance Scores

• loftool: 0.803
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.66

Haploinsufficiency Scores

• pHI: 0.876
• hipred: N
• hipred_score: 0.331
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Pgm1

Gene ontology

• Biological process: glycogen biosynthetic process;glycogen catabolic process;glucose metabolic process;gluconeogenesis;glycolytic process;galactose catabolic process;neutrophil degranulation
• Cellular component: extracellular region;cytoplasm;cytosol;actin cytoskeleton;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: magnesium ion binding;phosphoglucomutase activity;protein binding