PGM1

Summary

PGM1 (phosphoglucomutase 1, HGNC:8905) is a protein-coding gene on chromosome 1p31.3, encoding Phosphoglucomutase-1 (P36871). Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate.

The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red cells, PGM2 is a major isozyme. This gene is highly polymorphic. Mutations in this gene cause glycogen storage disease type 14. Alternativley spliced transcript variants encoding different isoforms have been identified in this gene.

Source: NCBI Gene 5236 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PGM1-congenital disorder of glycosylation (Definitive, ClinGen)
• GWAS associations: 8
• Clinical variants (ClinVar): 473 total — 25 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 47
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_002633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8905
Approved symbol	PGM1
Name	phosphoglucomutase 1
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000079739
Ensembl biotype	protein_coding
OMIM	171900
Entrez	5236

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000371083, ENST00000371084, ENST00000473117, ENST00000483707, ENST00000540265, ENST00000650546, ENST00000895882, ENST00000895883, ENST00000895884, ENST00000925889, ENST00000966605, ENST00000966606

RefSeq mRNA: 3 — MANE Select: NM_002633 NM_001172818, NM_001172819, NM_002633

CCDS: CCDS53323, CCDS53324, CCDS625

Canonical transcript exons

ENST00000371084 — 11 exons

Exon	Start	End
ENSE00000417363	63654332	63654466
ENSE00000773465	63634829	63635019
ENSE00000773466	63636234	63636388
ENSE00000773477	63638685	63638800
ENSE00000773484	63651669	63651852
ENSE00001219956	63648517	63648652
ENSE00001370961	63659586	63660245
ENSE00003491845	63631657	63631782
ENSE00003511758	63629425	63629587
ENSE00003648980	63629942	63630088
ENSE00003835263	63593411	63593734

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.7097 / max 800.1298, expressed in 1758 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3185	39.0909	1754
3184	3.2231	1327
3186	1.3768	617
3187	1.2955	847
3182	1.1257	814
3183	1.0018	733
201531	0.5027	252
3181	0.0731	27
3195	0.0202	10

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.70	gold quality
biceps brachii	UBERON:0001507	99.62	gold quality
vastus lateralis	UBERON:0001379	99.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.58	gold quality
quadriceps femoris	UBERON:0001377	99.57	gold quality
skeletal muscle tissue	UBERON:0001134	99.54	gold quality
gastrocnemius	UBERON:0001388	99.47	gold quality
gluteal muscle	UBERON:0002000	99.47	gold quality
triceps brachii	UBERON:0001509	99.46	gold quality
deltoid	UBERON:0001476	99.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.34	gold quality
diaphragm	UBERON:0001103	99.32	gold quality
muscle organ	UBERON:0001630	99.28	gold quality
tibialis anterior	UBERON:0001385	99.23	gold quality
body of tongue	UBERON:0011876	99.22	gold quality
muscle of leg	UBERON:0001383	99.17	gold quality
heart right ventricle	UBERON:0002080	98.90	gold quality
muscle tissue	UBERON:0002385	98.86	gold quality
left ventricle myocardium	UBERON:0006566	98.79	gold quality
myocardium	UBERON:0002349	98.57	gold quality
cartilage tissue	UBERON:0002418	98.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.08	gold quality
liver	UBERON:0002107	98.07	gold quality
apex of heart	UBERON:0002098	98.05	gold quality
cardiac ventricle	UBERON:0002082	97.99	gold quality
heart left ventricle	UBERON:0002084	97.97	gold quality
right lobe of liver	UBERON:0001114	97.63	gold quality
cardiac atrium	UBERON:0002081	97.53	gold quality
jejunal mucosa	UBERON:0000399	97.52	gold quality
right atrium auricular region	UBERON:0006631	97.48	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	114.41
E-CURD-114	no	18.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting PGM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-6847-5P	97.93	66.74	1808

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 26)

• The analysis involved the data on nine polymorphic codominant loci: HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD. The loci were selected by significance of differences in genotype frequencies between tuberculosis patients and healthy controls (PMID:12942785)
• cell signaling kinase Pak1 is a novel regulator of glucose metabolism through its phosphorylation and regulation of PGM activity. (PMID:15378030)
• Results report a novel human protein, calphoglin, which activates inorganic pyrophosphatase (IPP) and enhances phosphoglucomutase activity through the activated IPP. (PMID:15522220)
• During extrauterine life, females carrying the PGM1*2 allele are relatively protected from extreme body mass increase, and during intrauterine life, PGM1*2/*2 homozygotes show a tendency to low body mass increase. (PMID:18091362)
• There is a correlation between glomerular expression of MCP-1 and PGM1 and worsening renal prognosis in paediatric lupus nephritis. (PMID:18495743)
• ZASP/Cypher anchors PGM1 to Z-disc under conditions of stress. The impaired binding of PGM1 to ZASP/Cypher might be involved in the pathogenesis of dilated cardiomyopathy. (PMID:19377068)
• Phosphoglucomutase 1 deficiency, previously identified as a glycogenosis, is also a congenital disorder of glycosylation. (PMID:24499211)
• PGM1 is required for sustained cell growth during nutritional changes (PMID:24952355)
• both PGM1 protein misfolding and catalytic impairment may play a role in PGM1 deficiency (PMID:25288802)
• Homozygous mutation in the PGM1 gene is associated with PGM1 deficiency. (PMID:26768186)
• analysis of the structural basis of PGM1 enzyme dysfunction in PGM1 deficiency (PMID:26972339)
• The structural perturbation resulting from mutation of this single amino acid reveals the molecular mechanism underlying PGM1 deficiency in these missense variants. (PMID:28117557)
• PGM1 deficiency has been recognized as a cause of the congenital disorders of glycosylation. (PMID:29858906)
• Study examine variants within a substrate-binding loop in domain 4 (D4) of PGM1 that cause extreme impairment of activity. Multiple detrimental impacts were found including loss of conserved ligand-binding interactions and reduced mobility of the D4 loop, due to perturbation of its conformational ensemble. These potentially synergistic effects make this ligand-binding loop a hotspot for disease-related variants in PGM1. (PMID:30122451)
• We suggest that neurological symptoms are frequent in PGM1-CDG and could present even in the absence of hypoglycemia. The central nervous system should be assessed early on during the diagnostic process to optimize outcome in patients with PGM1-CDG. (PMID:30262252)
• Integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of hepatocellular carcinoma. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression. (PMID:30335765)
• c.405delT encodes a truncated protein with abnormal distribution and expression in skeletal muscle. (PMID:30737079)
• Variation in PGM-1 was associated with lower blood alcohol content in Korean subjects, suggesting likely involvement in alcohol metabolism and possible association with the development of alcohol-related diseases in Korea. (PMID:31002879)
• A genetic variant in the gene for phosphoglucomutase 1 (PGM1) was identified in the index patient and her two brothers, all were found to be homozygous for the genetic variant (G230E) NM_002633.2:c.689G>A in PGM1. This variant has been linked to a congenital disorder of glycosylation. Both parents and three other siblings were found to be heterozygous gene carriers without risk for the disease. (PMID:31563034)
• A missense variant remote from the active site impairs stability of human phosphoglucomutase 1. (PMID:32057119)
• AMPK-dependent phosphorylation of HDAC8 triggers PGM1 expression to promote lung cancer cell survival under glucose starvation. (PMID:32171858)
• Structural basis for substrate and product recognition in human phosphoglucomutase-1 (PGM1) isoform 2, a member of the alpha-D-phosphohexomutase superfamily. (PMID:32221390)
• Enzyme dysfunction at atomic resolution: Disease-associated variants of human phosphoglucomutase-1. (PMID:32898648)
• Phosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots. (PMID:33342467)
• Effects of the T337M and G391V disease-related variants on human phosphoglucomutase 1: structural disruptions large and small. (PMID:35506765)
• Knock-down of PGM1 inhibits cell viability, glycolysis, and oxidative phosphorylation in glioma under low glucose condition via the Myc signaling pathway. (PMID:36947965)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pgm1	ENSMUSG00000025791
rattus_norvegicus	Pgm1	ENSRNOG00000009889
drosophila_melanogaster	Pgm1	FBGN0003076
caenorhabditis_elegans		WBGENE00019890

Paralogs (6): PGM3 (ENSG00000013375), PRTFDC1 (ENSG00000099256), PGM5 (ENSG00000154330), PGM2L1 (ENSG00000165434), HPRT1 (ENSG00000165704), PGM2 (ENSG00000169299)

Protein

Protein identifiers

Phosphoglucomutase-1 — P36871 (reviewed: P36871)

Alternative names: Glucose phosphomutase 1

All UniProt accessions (2): P36871, A0A3B3ITK7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate. The mechanism proceeds via the intermediate compound alpha-D-glucose 1,6-bisphosphate. This enzyme participates in both the breakdown and synthesis of glucose.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylation at Thr-467 by PAK1 significantly enhances enzymatic activity.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Glucose-1,6-bisphosphate enhances phosphorylation of the active site Ser-117, and thereby increases enzyme activity.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Polymorphism. Many polymorphic variants of PGM1 exist. 8 different alleles are known: PGM11+, PGM11-, PGM12+, PGM12-, PGM13+, PGM13-, PGM17+ and PGM17-. The sequence of PGM1*1+ is shown here.

Similarity. Belongs to the phosphohexose mutase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P36871-1	1	yes
P36871-2	2
P36871-3	3

RefSeq proteins (3): NP_001166289, NP_001166290, NP_002624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005841	Alpha-D-phosphohexomutase_SF	Family
IPR005844	A-D-PHexomutase_a/b/a-I	Domain
IPR005845	A-D-PHexomutase_a/b/a-II	Domain
IPR005846	A-D-PHexomutase_a/b/a-III	Domain
IPR016055	A-D-PHexomutase_a/b/a-I/II/III	Homologous_superfamily
IPR016066	A-D-PHexomutase_CS	Conserved_site
IPR036900	A-D-PHexomutase_C_sf	Homologous_superfamily
IPR045244	PGM	Family

Pfam: PF02878, PF02879, PF02880, PF24947

Enzyme classification (BRENDA):

• EC 5.4.2.2 — phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate-dependent) (BRENDA: 53 organisms, 77 substrates, 56 inhibitors, 76 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALPHA-D-GLUCOSE 1-PHOSPHATE	0.0006–3.53	46
D-GLUCOSE 6-PHOSPHATE	2–13	7
ALPHA-D-MANNOSE 1-PHOSPHATE	0.4392–1.15	3
D-GLUCOSE-1-PHOSPHATE	0.0952–3	3
ALPHA-D-GLUCOSE 1,6-BISPHOSPHATE	0.016–0.033	2
D-MANNOSE-1-PHOSPHATE	0.0915–3.2	2
2-DEOXYRIBOSE-1-PHOSPHATE	3.5	1
D-GLUCOSE 1,6-DIPHOSPHATE	0.001	1
D-MANNOSE 1-PHOSPHATE	0.02	1
GLUCOSE 1-PHOSPHATE	0.022	1
MANNOSE 1-PHOSPHATE	0.017	1

Catalyzed reactions (Rhea), 3 shown:

• alpha-D-glucose 1-phosphate = alpha-D-glucose 6-phosphate (RHEA:23536)
• O-phospho-L-seryl-[protein] + alpha-D-glucose 1-phosphate = alpha-D-glucose 1,6-bisphosphate + L-seryl-[protein] (RHEA:68748)
• alpha-D-glucose 1,6-bisphosphate + L-seryl-[protein] = O-phospho-L-seryl-[protein] + alpha-D-glucose 6-phosphate (RHEA:68752)

UniProt features (119 total): strand 30, helix 24, modified residue 22, sequence variant 18, binding site 12, turn 8, splice variant 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5JN5	X-RAY DIFFRACTION	1.75
5VBI	X-RAY DIFFRACTION	1.75
5EPC	X-RAY DIFFRACTION	1.85
5VG7	X-RAY DIFFRACTION	1.95
6UO6	X-RAY DIFFRACTION	2.15
5VEC	X-RAY DIFFRACTION	2.2
6UIQ	X-RAY DIFFRACTION	2.3
5F9C	X-RAY DIFFRACTION	2.5
5TR2	X-RAY DIFFRACTION	2.5
7S0W	X-RAY DIFFRACTION	2.5
5VIN	X-RAY DIFFRACTION	2.6
5HSH	X-RAY DIFFRACTION	2.65
6SNO	X-RAY DIFFRACTION	2.7
6SNQ	X-RAY DIFFRACTION	2.7
6SNP	X-RAY DIFFRACTION	2.75
7S77	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36871-F1	97.27	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 117 (phosphoserine intermediate)

Ligand- & substrate-binding residues (12): 357; 376; 378; 389; 23; 117; 117 (via phosphate groupe); 288; 290; 292; 292; 293

Post-translational modifications (22): 1, 1, 16, 115, 117, 134, 185, 201, 206, 213, 349, 353, 369, 378, 419, 467, 477, 485, 505, 507 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3322077	Glycogen synthesis
R-HSA-5609974	Defective PGM1 causes PGM1-CDG
R-HSA-6798695	Neutrophil degranulation
R-HSA-70221	Glycogen breakdown (glycogenolysis)
R-HSA-70370	Galactose catabolism

MSigDB gene sets: 387 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_SECRETORY_GRANULE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GTGCCTT_MIR506

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), glycogen catabolic process (GO:0005980), glucose metabolic process (GO:0006006), gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), beta-D-galactose catabolic process via UDP-galactose, Leloir pathway (GO:0033499)

GO Molecular Function (6): magnesium ion binding (GO:0000287), phosphoglucomutase activity (GO:0004614), protein binding (GO:0005515), isomerase activity (GO:0016853), intramolecular phosphotransferase activity (GO:0016868), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycogen metabolism	2
Diseases associated with glycosylation precursor biosynthesis	1
Innate Immune System	1
Metabolism of carbohydrates and carbohydrate derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular organelle lumen	2
primary metabolic process	1
glycogen metabolic process	1
glucan catabolic process	1
hexose metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
galactose catabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
metal ion binding	1
intramolecular phosphotransferase activity	1
binding	1
catalytic activity	1
intramolecular transferase activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGM1	PGM2	Q96G03	968
PGM1	PGD	P52209	943
PGM1	PGM3	O95394	918
PGM1	ENO1	P06733	857
PGM1	AK2	P54819	848
PGM1	PGC	P20142	830
PGM1	FUCA1	P04066	829
PGM1	ESD	P10768	777
PGM1	CD68	P34810	776
PGM1	ENO3	P13929	773
PGM1	AK1	P00568	761
PGM1	GLO1	P78375	702
PGM1	C8B	P07358	697
PGM1	UGP2	Q16851	690
PGM1	HSPA6	P17066	672

IntAct

40 interactions, top by confidence:

A	B	Type	Score
PGM1	TINF2	psi-mi:“MI:0915”(physical association)	0.510
TERF1	PGM1	psi-mi:“MI:0915”(physical association)	0.370
TERF2IP	PGM1	psi-mi:“MI:0915”(physical association)	0.370
PGM1	POT1	psi-mi:“MI:0915”(physical association)	0.370
HSCB	PGM1	psi-mi:“MI:0915”(physical association)	0.370
HSPB2	PGM1	psi-mi:“MI:0915”(physical association)	0.370
PAK1	PGM1	psi-mi:“MI:0915”(physical association)	0.370
PGM1		psi-mi:“MI:0915”(physical association)	0.370
LRRK2		psi-mi:“MI:0914”(association)	0.350
PGM1	Nck1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
UBA5	PGK1	psi-mi:“MI:0914”(association)	0.350
IGF1R	GLRX3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RPS11	SCAMP1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
MAVS	CHMP2A	psi-mi:“MI:0914”(association)	0.350
CSDE1	VPS37C	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPS23	MYH7B	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
SNRNP27	BPNT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (158): PGM1 (Affinity Capture-MS), ATIC (Co-fractionation), CAT (Co-fractionation), ENO1 (Co-fractionation), EXOC2 (Co-fractionation), GALK2 (Co-fractionation), GPI (Co-fractionation), GRHPR (Co-fractionation), LTA4H (Co-fractionation), PGM1 (Co-fractionation), PGM1 (Co-fractionation), PGM1 (Co-fractionation), PGM1 (Co-fractionation), PGM1 (Co-fractionation), PGM1 (Co-fractionation)

ESM2 similar proteins: A5A6K8, B9N1F9, O49299, P00503, P00504, P00949, P05201, P08906, P13221, P17174, P18757, P28011, P28734, P33097, P36871, P37833, P38652, P40939, P46645, P49724, P54767, P93804, P93805, Q01912, Q08DP0, Q0P5G4, Q28BL6, Q4R5E4, Q4R5L1, Q58FK9, Q5E9N4, Q5R691, Q5RFI8, Q640V9, Q6GML7, Q6YP21, Q71RI9, Q7T3E5, Q7TSV4, Q8N5Z0

Diamond homologs: A0A2R6W0K6, D3ZVR9, O02606, O15820, O18719, O49299, O74374, P00949, P33401, P36871, P37012, P38652, P39671, P47244, P57749, P93262, P93804, P93805, Q08DP0, Q116W4, Q15124, Q23919, Q4R5E4, Q4WY53, Q890U1, Q8BZF8, Q97LS0, Q9D0F9, Q9M4G4, Q9M4G5, Q9P931, Q9SCY0, Q9SGC1, Q9SM59, Q9SM60, Q9SMM0, Q9SNX2, Q9VUY9, Q9ZSQ4, A0KNE8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PAK1	up-regulates	PGM1	phosphorylation
PKN1	up-regulates	PGM1	phosphorylation
PGM1	“up-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
PGM1	“up-regulates quantity”	“alpha-D-glucose 6-phosphate(2-)”	“chemical modification”
PGM1	“down-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
PGM1	“down-regulates quantity”	“alpha-D-glucose 6-phosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

473 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	8
Uncertain significance	161
Likely benign	171
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064684	PGM1, ARG521TER	Pathogenic
1302006	NM_002633.3(PGM1):c.423del (p.Ala142fs)	Pathogenic
133286	NM_002633.3(PGM1):c.1547T>C (p.Leu516Pro)	Pathogenic
133290	NM_002633.3(PGM1):c.661del (p.Arg221fs)	Pathogenic
13650	NM_002633.3(PGM1):c.343A>G (p.Thr115Ala)	Pathogenic
13651	NM_002633.3(PGM1):c.1145-1G>C	Pathogenic
1383900	NM_002633.3(PGM1):c.929_930del (p.Val310fs)	Pathogenic
1442891	NM_002633.3(PGM1):c.1474del (p.Leu492fs)	Pathogenic
1803009	NM_002633.3(PGM1):c.689dup (p.Pro231fs)	Pathogenic
1803010	NM_002633.3(PGM1):c.696_699del (p.Pro231_Tyr232insTer)	Pathogenic
2013476	NM_002633.3(PGM1):c.511G>T (p.Gly171Ter)	Pathogenic
2581183	NM_002633.3(PGM1):c.87_94del (p.Phe29fs)	Pathogenic
2696539	NM_002633.3(PGM1):c.1500del (p.Ile500fs)	Pathogenic
2792756	NM_002633.3(PGM1):c.946_997dup (p.Arg333fs)	Pathogenic
3247792	NC_000001.10:g.(?64119983)(64125346_?)del	Pathogenic
3727616	NM_002633.3(PGM1):c.1422dup (p.Glu475Ter)	Pathogenic
39771	NM_002633.3(PGM1):c.361G>C (p.Gly121Arg)	Pathogenic
39772	NM_002633.3(PGM1):c.1507C>T (p.Arg503Ter)	Pathogenic
4291923	NM_002633.3(PGM1):c.1519_1545delinsC (p.Thr507fs)	Pathogenic
4750835	NM_002633.3(PGM1):c.313A>T (p.Lys105Ter)	Pathogenic
499573	NM_002633.3(PGM1):c.649C>T (p.Arg217Ter)	Pathogenic
579973	NM_002633.3(PGM1):c.1091del (p.Asn364fs)	Pathogenic
645088	NM_002633.3(PGM1):c.1378_1379del (p.Ala461fs)	Pathogenic
654351	NM_002633.3(PGM1):c.1086dup (p.Gly363fs)	Pathogenic
663105	NM_002633.3(PGM1):c.87_88del (p.Phe29fs)	Pathogenic
1066321	NM_002633.3(PGM1):c.1281-2A>G	Likely pathogenic
2690669	NM_002633.3(PGM1):c.689G>A (p.Gly230Glu)	Likely pathogenic
3769186	NM_002633.3(PGM1):c.1464+1G>A	Likely pathogenic
3780115	NM_002633.3(PGM1):c.1508G>A (p.Arg503Gln)	Likely pathogenic
4627346	NM_002633.3(PGM1):c.1588C>T (p.Gln530Ter)	Likely pathogenic

SpliceAI

2364 predictions. Top by Δscore:

Variant	Effect	Δscore
1:63593732:GGG:G	donor_gain	1.0000
1:63593733:GGG:G	donor_gain	1.0000
1:63629421:CTA:C	acceptor_loss	1.0000
1:63629423:A:AG	acceptor_gain	1.0000
1:63629423:AGATC:A	acceptor_gain	1.0000
1:63629424:G:GG	acceptor_gain	1.0000
1:63629424:GATC:G	acceptor_gain	1.0000
1:63629424:GATCG:G	acceptor_gain	1.0000
1:63629936:TTCCA:T	acceptor_loss	1.0000
1:63629938:CCA:C	acceptor_loss	1.0000
1:63629941:G:GT	acceptor_loss	1.0000
1:63630022:A:T	donor_gain	1.0000
1:63630064:GAAAA:G	donor_gain	1.0000
1:63630065:A:T	donor_gain	1.0000
1:63630068:A:AG	donor_gain	1.0000
1:63630068:A:G	donor_gain	1.0000
1:63631636:T:TA	acceptor_gain	1.0000
1:63631642:T:A	acceptor_gain	1.0000
1:63631655:A:AC	acceptor_loss	1.0000
1:63631655:A:AG	acceptor_gain	1.0000
1:63631655:AGT:A	acceptor_gain	1.0000
1:63631655:AGTG:A	acceptor_gain	1.0000
1:63631656:G:GT	acceptor_gain	1.0000
1:63631656:GT:G	acceptor_gain	1.0000
1:63631656:GTG:G	acceptor_gain	1.0000
1:63631656:GTGG:G	acceptor_gain	1.0000
1:63631656:GTGGA:G	acceptor_gain	1.0000
1:63631780:G:GT	donor_gain	1.0000
1:63631780:G:T	donor_gain	1.0000
1:63631780:GAGGT:G	donor_loss	1.0000

AlphaMissense

3713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:63593549:G:T	G21W	1.000
1:63593550:G:A	G21E	1.000
1:63629527:A:C	S117R	1.000
1:63629528:G:T	S117I	1.000
1:63629529:T:A	S117R	1.000
1:63629529:T:G	S117R	1.000
1:63629530:C:G	H118D	1.000
1:63629532:C:A	H118Q	1.000
1:63629532:C:G	H118Q	1.000
1:63629561:G:A	G128E	1.000
1:63629566:A:G	K130E	1.000
1:63634937:C:A	P264H	1.000
1:63635008:G:C	D288H	1.000
1:63635009:A:T	D288V	1.000
1:63635010:T:A	D288E	1.000
1:63635010:T:G	D288E	1.000
1:63635014:G:C	D290H	1.000
1:63635015:A:T	D290V	1.000
1:63636235:A:C	D292A	1.000
1:63636235:A:T	D292V	1.000
1:63636238:G:C	R293P	1.000
1:63638731:T:A	W359R	1.000
1:63638731:T:C	W359R	1.000
1:63638788:A:C	S378R	1.000
1:63638790:C:A	S378R	1.000
1:63638790:C:G	S378R	1.000
1:63648564:T:A	W398R	1.000
1:63648564:T:C	W398R	1.000
1:63648652:G:T	R427M	1.000
1:63593546:A:C	S20R	0.999

dbSNP variants (sampled 300 via entrez): RS1000004544 (1:63615698 G>C), RS1000005632 (1:63623149 C>T), RS1000119618 (1:63655946 G>A), RS1000290199 (1:63599482 G>C,T), RS1000365085 (1:63607179 G>A), RS1000556480 (1:63625841 C>T), RS1000666183 (1:63640355 G>A), RS1000681746 (1:63613100 A>G), RS1000727497 (1:63629699 G>A), RS1000735332 (1:63641522 A>G), RS1000753029 (1:63600127 C>T), RS1000850009 (1:63646846 C>A,T), RS1000856126 (1:63595194 G>A), RS1000924818 (1:63644729 T>C), RS1000928021 (1:63597765 G>A,T)

Disease associations

OMIM: gene MIM:171900 | disease phenotypes: MIM:614921

GenCC curated gene-disease

Disease	Classification	Inheritance
PGM1-congenital disorder of glycosylation	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
PGM1-congenital disorder of glycosylation	Definitive	AR

Mondo (2): PGM1-congenital disorder of glycosylation (MONDO:0013968), congenital disorder of glycosylation (MONDO:0015286)

Orphanet (2): PGM1-CDG (Orphanet:319646), Congenital disorder of glycosylation (Orphanet:137)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000201	Pierre-Robin sequence
HP:0000347	Micrognathia
HP:0000403	Recurrent otitis media
HP:0000592	Blue sclerae
HP:0000823	Delayed puberty
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001324	Muscle weakness
HP:0001397	Hepatic steatosis
HP:0001406	Intrahepatic cholestasis
HP:0001510	Growth delay
HP:0001629	Ventricular septal defect
HP:0001640	Cardiomegaly
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001649	Tachycardia
HP:0001680	Coarctation of aorta
HP:0001943	Hypoglycemia
HP:0001976	Reduced antithrombin III activity
HP:0002013	Vomiting
HP:0002028	Chronic diarrhea
HP:0002047	Malignant hyperthermia
HP:0002092	Pulmonary arterial hypertension
HP:0002094	Dyspnea
HP:0002240	Hepatomegaly

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000392_16	Type 1 diabetes	4.000000e-07
GCST001103_6	Alcohol consumption (transferrin glycosylation)	2.000000e-09
GCST010118_5	Type 2 diabetes	5.000000e-10
GCST010681_1	Type 1 diabetes	1.000000e-10
GCST90000529_3	Type 1 diabetes	2.000000e-06
GCST90013445_26	Type 1 diabetes	5.000000e-12
GCST90013445_42	Type 1 diabetes	5.000000e-12
GCST90014023_12	Type 1 diabetes	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125
C567859	Glycogen Storage Disease XIV (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4643	Metabolism/PK	3	acetaldehyde

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4643	PGM1	3	1.50	1	acetaldehyde

CTD chemical–gene interactions

83 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	8
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	increases expression, decreases expression	4
Arsenic Trioxide	affects cotreatment, affects binding, decreases reaction, decreases expression, increases reaction (+1 more)	4
trichostatin A	affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
methylmercuric chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Oxygen	increases expression	2
Rotenone	increases expression	2
Tretinoin	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
alpha-naphthoflavone	decreases expression, decreases reaction, increases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	decreases reaction, increases expression	1
cobaltous chloride	increases expression, decreases reaction	1
linalool	increases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	increases expression	1
dinophysistoxin 1	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism