PGM3

Summary

PGM3 (phosphoglucomutase 3, HGNC:8907) is a protein-coding gene on chromosome 6q14.1, encoding Phosphoacetylglucosamine mutase (O95394). Catalyzes the conversion of GlcNAc-6-P into GlcNAc-1-P during the synthesis of uridine diphosphate/UDP-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways including protein N- and O-glycosylation. It is a selective cancer dependency (DepMap: 25.0% of cell lines).

This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5238 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 23 (Definitive, ClinGen)
• Clinical variants (ClinVar): 538 total — 45 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 87
• Cancer dependency (DepMap): dependent in 25.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_015599

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8907
Approved symbol	PGM3
Name	phosphoglucomutase 3
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	AGM1, DKFZP434B187, PAGM
Ensembl gene	ENSG00000013375
Ensembl biotype	protein_coding
OMIM	172100
Entrez	5238

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 41 protein_coding, 19 nonsense_mediated_decay, 10 retained_intron

ENST00000283977, ENST00000503094, ENST00000504780, ENST00000505470, ENST00000506587, ENST00000507404, ENST00000507554, ENST00000508748, ENST00000509219, ENST00000510258, ENST00000512866, ENST00000513973, ENST00000515333, ENST00000605602, ENST00000616566, ENST00000650640, ENST00000650642, ENST00000651204, ENST00000651425, ENST00000651698, ENST00000652222, ENST00000652468, ENST00000698524, ENST00000698525, ENST00000698526, ENST00000698599, ENST00000698600, ENST00000698601, ENST00000698602, ENST00000698603, ENST00000698604, ENST00000698605, ENST00000698606, ENST00000698607, ENST00000698608, ENST00000698609, ENST00000698610, ENST00000698611, ENST00000698612, ENST00000698613, ENST00000698614, ENST00000698615, ENST00000698616, ENST00000698617, ENST00000698618, ENST00000698619, ENST00000698620, ENST00000698621, ENST00000698622, ENST00000698623, ENST00000879094, ENST00000879095, ENST00000925371, ENST00000925372, ENST00000925373, ENST00000925374, ENST00000925375, ENST00000925376, ENST00000925377, ENST00000925378, ENST00000925379, ENST00000925380, ENST00000941524, ENST00000941525, ENST00000941526, ENST00000941527, ENST00000941528, ENST00000941529, ENST00000941530, ENST00000941531

RefSeq mRNA: 6 — MANE Select: NM_015599 NM_001199917, NM_001199918, NM_001199919, NM_001367286, NM_001367287, NM_015599

CCDS: CCDS4997, CCDS56435, CCDS56436, CCDS75487, CCDS93954

Canonical transcript exons

ENST00000513973 — 13 exons

Exon	Start	End
ENSE00000759985	83171937	83172059
ENSE00000759986	83174374	83174487
ENSE00000759988	83175962	83176060
ENSE00002058845	83164873	83169323
ENSE00003973896	83187008	83187075
ENSE00003973897	83170305	83170478
ENSE00003973899	83181736	83181931
ENSE00003973900	83182845	83182978
ENSE00003973904	83190809	83191014
ENSE00003973905	83188614	83188798
ENSE00003974120	83178673	83178756
ENSE00003974145	83193179	83193265
ENSE00003974148	83179810	83179967

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 97.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5930 / max 509.6753, expressed in 1791 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74550	27.5592	1791
74551	0.0338	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.68	gold quality
pancreas	UBERON:0001264	96.03	gold quality
islet of Langerhans	UBERON:0000006	95.93	gold quality
stromal cell of endometrium	CL:0002255	95.75	gold quality
adenohypophysis	UBERON:0002196	94.66	gold quality
calcaneal tendon	UBERON:0003701	94.44	gold quality
cartilage tissue	UBERON:0002418	94.29	gold quality
pituitary gland	UBERON:0000007	93.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.98	gold quality
adrenal tissue	UBERON:0018303	92.91	gold quality
left ovary	UBERON:0002119	92.64	gold quality
sperm	CL:0000019	92.60	gold quality
minor salivary gland	UBERON:0001830	92.57	gold quality
gall bladder	UBERON:0002110	92.54	gold quality
right ovary	UBERON:0002118	92.54	gold quality
rectum	UBERON:0001052	92.42	gold quality
right lobe of liver	UBERON:0001114	92.22	gold quality
left adrenal gland	UBERON:0001234	91.73	gold quality
left adrenal gland cortex	UBERON:0035825	91.71	gold quality
saliva-secreting gland	UBERON:0001044	91.69	gold quality
left testis	UBERON:0004533	91.56	gold quality
endocervix	UBERON:0000458	91.50	gold quality
right testis	UBERON:0004534	91.46	gold quality
omental fat pad	UBERON:0010414	91.43	gold quality
peritoneum	UBERON:0002358	91.39	gold quality
upper lobe of left lung	UBERON:0008952	91.31	gold quality
ascending aorta	UBERON:0001496	91.27	gold quality
right adrenal gland	UBERON:0001233	91.16	gold quality
thoracic aorta	UBERON:0001515	91.08	gold quality
prostate gland	UBERON:0002367	91.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

163 targeting PGM3, 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-340-5P	100.00	72.50	4437
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-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6809-3P	99.91	71.45	3814

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 25.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• PGM(3) is identical to AGM(1). (PMID:12174217)
• Polymorphic analysis of the human phosphoglucomutase-3 gene. (PMID:20221814)
• Autosomal recessive hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability, and hypomyelination. (PMID:24589341)
• Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. (PMID:24698316)
• define PGM3-CDG as a treatable immunodeficiency, document the power of whole-exome sequencing in gene discoveries for rare disorders, and illustrate the utility of genomic analyses in studying combined and variable phenotypes (PMID:24931394)
• Data indicate the effect of the phosphoglucomutase 3 (PGM3) mutation for four immunodeficient siblings in a Swedish family. (PMID:26482871)
• PGM3 mutation identified in a patient with hyper IgE syndrome results in lack of glycosylation at Asn264 and altered glycosylation profile. (PMID:26687240)
• Novel PGM3 Mutation Is Associated With a Severe Phenotype of Bone Marrow Failure, Severe Combined Immunodeficiency, Skeletal Dysplasia, and Congenital Malformations. (PMID:28543917)
• study reports the first founder mutation in PGM3 gene (p.Glu340del) in twelve Tunisian PGM3 deficient patients belonging to three consanguineous families originating from a rural district in west central Tunisia (PMID:28704707)
• our findings demonstrate that defective glycosylation in PGM3-deficient patients results in reduced expression of unglycosylated gp130 protein and consequently, impaired gp130-dependent STAT3 phosphorylation. (PMID:30578875)
• Deficiency of phosphoglucomutase 3 (PGM3) is an autosomal recessive disorder of N- and O-glycosylation. (PMID:31231132)
• Compound Heterozygous PGM3 Mutations in a Thai Patient with a Specific Antibody Deficiency Requiring Monthly IVIG Infusions. (PMID:31707513)
• Targeting PGM3 as a Novel Therapeutic Strategy in KRAS/LKB1 Co-Mutant Lung Cancer. (PMID:35011738)
• PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression. (PMID:35723049)
• Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients. (PMID:36768728)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgm3	ENSDARG00000024654
mus_musculus	Pgm3	ENSMUSG00000056131
rattus_norvegicus	Pgm3	ENSRNOG00000009515
drosophila_melanogaster	nst	FBGN0036298
caenorhabditis_elegans		WBGENE00009006

Paralogs (6): PGM1 (ENSG00000079739), PRTFDC1 (ENSG00000099256), PGM5 (ENSG00000154330), PGM2L1 (ENSG00000165434), HPRT1 (ENSG00000165704), PGM2 (ENSG00000169299)

Protein

Protein identifiers

Phosphoacetylglucosamine mutase — O95394 (reviewed: O95394)

Alternative names: Acetylglucosamine phosphomutase, N-acetylglucosamine-phosphate mutase, Phosphoglucomutase-3

All UniProt accessions (24): O95394, A0A087WT27, A0A494C099, A0A494C0G1, A0A494C163, A0A494C1E2, A0A494C1Q4, A0A8V8TLT8, A0A8V8TM25, A0A8V8TMH7, A0A8V8TMI1, A0A8V8TNG4, A0A8V8TNH4, A0A8V8TNM1, A0A8V8TNT6, D6RC77, D6RCD1, D6RCQ8, D6RF77, D6RIS6, H0Y8I3, H0Y987, J3KN95, S4R390

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of GlcNAc-6-P into GlcNAc-1-P during the synthesis of uridine diphosphate/UDP-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways including protein N- and O-glycosylation.

Tissue specificity. Found in many tissues except lung. Relatively high expression in pancreas, heart, liver, and placenta, and relatively low expression in brain, skeletal muscle and kidney.

Disease relevance. Immunodeficiency 23 (IMD23) [MIM:615816] A primary immunodeficiency syndrome characterized by recurrent respiratory and skin infections beginning in early childhood, severe atopy, increased serum IgE, and developmental delay or cognitive impairment of varying severity. The disease is caused by variants affecting the gene represented in this entry.

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

Pathway. Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-glucosamine biosynthesis; N-acetyl-alpha-D-glucosamine 1-phosphate from alpha-D-glucosamine 6-phosphate (route I): step 2/2.

Similarity. Belongs to the phosphohexose mutase family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95394-1	1	yes
O95394-3	2
O95394-4	3

RefSeq proteins (6): NP_001186846, NP_001186847, NP_001186848, NP_001354215, NP_001354216, NP_056414* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005843	A-D-PHexomutase_C	Domain
IPR005844	A-D-PHexomutase_a/b/a-I	Domain
IPR016055	A-D-PHexomutase_a/b/a-I/II/III	Homologous_superfamily
IPR016066	A-D-PHexomutase_CS	Conserved_site
IPR016657	PAGM	Family
IPR036900	A-D-PHexomutase_C_sf	Homologous_superfamily
IPR049022	AMG1_III	Domain
IPR049023	AMG1_II	Domain

Pfam: PF00408, PF02878, PF21404, PF21405

Enzyme classification (BRENDA):

• EC 5.4.2.3 — phosphoacetylglucosamine mutase (BRENDA: 14 organisms, 23 substrates, 20 inhibitors, 11 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GLUCOSE 1-PHOSPHATE	0.39–0.658	2
N-ACETYLGLUCOSAMINE 1-PHOSPHATE	0.0237–0.29	2
ALPHA-D-GLUCOSE 1-PHOSPHATE	0.6792	1
D-GLUCOSE-1-PHOSPHATE	0.54	1
N-ACETYL-ALPHA-D-GLUCOSAMINE	0.046	1
N-ACETYL-ALPHA-D-GLUCOSAMINE 1-PHOSPHATE	0.7	1
N-ACETYL-D-GLUCOSAMINE 6-PHOSPHATE	0.014	1
N-ACETYLGLUCOSAMINE 6-PHOSPHATE	3.6	1
N-ACETYLGLUCOSAMINE-1-PHOSPHATE	0.046	1

Catalyzed reactions (Rhea), 1 shown:

• N-acetyl-alpha-D-glucosamine 1-phosphate = N-acetyl-D-glucosamine 6-phosphate (RHEA:23804)

UniProt features (29 total): sequence variant 9, binding site 7, mutagenesis site 4, modified residue 3, splice variant 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95394-F1	95.54	0.93

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): 64 (phosphoserine intermediate)

Ligand- & substrate-binding residues (7): 64 (via phosphate group); 276; 278; 280; 370–372; 496–500; 505

Post-translational modifications (3): 62, 64, 1

Mutagenesis-validated functional residues (4):

Position	Phenotype
64	loss of activity.
65	loss of activity.
278	loss of activity.
281	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-446210	Synthesis of UDP-N-acetyl-glucosamine
R-HSA-392499	Metabolism of proteins
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 382 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MORF_MSH3, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, MORF_BRCA1, GOZGIT_ESR1_TARGETS_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_AMINO_SUGAR_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, MORF_RAD51L3, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (9): carbohydrate metabolic process (GO:0005975), D-glucosamine metabolic process (GO:0006041), UDP-N-acetylglucosamine biosynthetic process (GO:0006048), protein N-linked glycosylation (GO:0006487), protein O-linked glycosylation (GO:0006493), spermatogenesis (GO:0007283), hemopoiesis (GO:0030097), amino sugar biosynthetic process (GO:0046349), cell wall organization (GO:0071555)

GO Molecular Function (5): magnesium ion binding (GO:0000287), phosphoacetylglucosamine mutase activity (GO:0004610), isomerase activity (GO:0016853), intramolecular phosphotransferase activity (GO:0016868), metal ion binding (GO:0046872)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
amino sugar metabolic process	2
glycoprotein biosynthetic process	2
primary metabolic process	1
UDP-N-acetylglucosamine metabolic process	1
nucleotide-sugar biosynthetic process	1
amino sugar biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
cell development	1
carbohydrate derivative biosynthetic process	1
external encapsulating structure organization	1
cell wall organization or biogenesis	1
metal ion binding	1
intramolecular phosphotransferase activity	1
catalytic activity	1
intramolecular transferase activity	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGM3	PGM2	Q96G03	929
PGM3	PGM1	P36871	918
PGM3	PGM5	Q15124	886
PGM3	IGLL1	P15814	879
PGM3	UAP1	Q16222	849
PGM3	GNPNAT1	Q96EK6	841
PGM3	GLO1	P78375	824
PGM3	GFPT1	Q06210	773
PGM3	GFPT2	O94808	731
PGM3	ME1	P48163	712
PGM3	LRRC8A	Q8IWT6	692
PGM3	NAGK	Q9UJ70	689
PGM3	PGD	P52209	682
PGM3	DOCK8	Q8NF50	677
PGM3	HLA-A	P01891	671

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
GPR17	IPO8	psi-mi:“MI:0914”(association)	0.530
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
ERBB2	PGM3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
COMTD1	TARS3	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
AQP3	UBXN8	psi-mi:“MI:0914”(association)	0.350
VIPR1	SLC33A1	psi-mi:“MI:0914”(association)	0.350
SLC2A1	SLC33A1	psi-mi:“MI:0914”(association)	0.350
FPR1	RAB29	psi-mi:“MI:0914”(association)	0.350
LYPD1	LRP5	psi-mi:“MI:0914”(association)	0.350
SLC15A1	MEN1	psi-mi:“MI:0914”(association)	0.350
SLC35B4	PSMD11	psi-mi:“MI:0914”(association)	0.350
SLC7A11	PSMD9	psi-mi:“MI:0914”(association)	0.350
LRRK2	SF3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (102): ENOPH1 (Co-fractionation), HDHD1 (Co-fractionation), LACTB2 (Co-fractionation), PGM3 (Co-fractionation), PGM3 (Co-fractionation), PGM3 (Co-fractionation), PGM3 (Co-fractionation), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS), PGM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4BZI5, A7M6E7, A7M6E8, B4G0F3, B8BKI7, B9SQI7, C6JS30, F4JGR5, F4JP46, F4JVN6, O04015, O04226, O65361, O80574, O95394, P11172, P31754, P32296, P69060, Q10P67, Q10S55, Q28EN2, Q2R483, Q32LQ4, Q3SZM5, Q53JY8, Q5R514, Q5R6R5, Q5RAK7, Q5RF32, Q5XGM3, Q6P6M7, Q6STH5, Q8GSJ1, Q8LAX0, Q8LB01, Q8NFW8, Q90WG6, Q91WS4, Q94A08

Diamond homologs: F1RQM2, O95394, P38628, P57750, Q09687, Q09770, Q6ZDQ1, Q8SSL7, Q9CYR6, Q9P4V2, Q9UZT5, A9W9G7, B0ULF6, B2IGB3, B3PYX0, B5ZNL4, B7KWJ1, B9J9H0, Q0ALR7, Q0BT42, Q11DI7, Q1GUJ4, Q2GB44, Q2K4M3, Q2RVE4, Q4FN15, B9JRY5, Q6FYQ7, B8DN76, A0QSQ1, A1T554, A1UC06, A1WEE4, A3PVN7, A4TEL0, Q1BCY7, Q7NRI6, A4FX97, A6UP86, A6VG24

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	11
Uncertain significance	168
Likely benign	270
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071144	NM_015599.3(PGM3):c.421dup (p.Ile141fs)	Pathogenic
1071477	NM_015599.3(PGM3):c.784C>T (p.Gln262Ter)	Pathogenic
1073418	NM_015599.3(PGM3):c.767_777del (p.Ser256fs)	Pathogenic
133317	NM_015599.3(PGM3):c.1354_1358del (p.Leu452fs)	Pathogenic
133318	NM_015599.3(PGM3):c.891T>G (p.Asp297Glu)	Pathogenic
133319	NM_015599.3(PGM3):c.1020_1022del (p.Glu340_Val341delinsAsp)	Pathogenic
133320	NM_015599.3(PGM3):c.248T>C (p.Leu83Ser)	Pathogenic
1350279	NM_015599.3(PGM3):c.-2-238del	Pathogenic
140734	NM_015599.3(PGM3):c.737dup (p.Asn246fs)	Pathogenic
140735	NM_015599.3(PGM3):c.1352A>G (p.Gln451Arg)	Pathogenic
1412911	NM_015599.3(PGM3):c.1330_1333dup (p.Thr445fs)	Pathogenic
1419730	NC_000006.11:g.(?83878953)(83900987_?)del	Pathogenic
1912110	NM_015599.3(PGM3):c.-2-195C>G	Pathogenic
2096756	NM_015599.3(PGM3):c.1104T>G (p.Tyr368Ter)	Pathogenic
224830	NM_015599.3(PGM3):c.715G>C (p.Asp239His)	Pathogenic
2691540	NM_015599.3(PGM3):c.162del (p.Lys54fs)	Pathogenic
2709928	NM_015599.3(PGM3):c.322_323insGATTG (p.Asp108fs)	Pathogenic
2727774	NM_015599.3(PGM3):c.-2-242_-2-241del	Pathogenic
2739581	NM_015599.3(PGM3):c.1255_1277del (p.Asp418_Ala419insTer)	Pathogenic
2745927	NM_015599.3(PGM3):c.152_153del (p.Lys51fs)	Pathogenic
2808030	NM_015599.3(PGM3):c.620C>G (p.Ser207Ter)	Pathogenic
2821069	NM_015599.3(PGM3):c.1359dup (p.Val454fs)	Pathogenic
2836292	NM_015599.3(PGM3):c.162dup (p.Ser55fs)	Pathogenic
2839320	NM_015599.3(PGM3):c.908del (p.Thr303fs)	Pathogenic
2839660	NM_015599.3(PGM3):c.43_46dup (p.Pro16fs)	Pathogenic
2861234	NM_015599.3(PGM3):c.-2-218G>T	Pathogenic
2863785	NM_015599.3(PGM3):c.816C>A (p.Cys272Ter)	Pathogenic
2888196	NM_015599.3(PGM3):c.1165_1166del (p.Gln389fs)	Pathogenic
2896746	NM_015599.3(PGM3):c.1197_1201del (p.Arg399fs)	Pathogenic
2905265	NM_015599.3(PGM3):c.563_564del (p.Leu187_Ser188insTer)	Pathogenic

SpliceAI

4882 predictions. Top by Δscore:

Variant	Effect	Δscore
6:83148754:TGCA:T	acceptor_loss	1.0000
6:83148755:GCA:G	acceptor_loss	1.0000
6:83148756:CAG:C	acceptor_loss	1.0000
6:83148757:A:AG	acceptor_gain	1.0000
6:83148758:G:GG	acceptor_gain	1.0000
6:83148758:GA:G	acceptor_gain	1.0000
6:83148862:GG:G	donor_gain	1.0000
6:83148863:GG:G	donor_gain	1.0000
6:83151878:TTTAG:T	acceptor_loss	1.0000
6:83151879:TTA:T	acceptor_loss	1.0000
6:83151881:A:AC	acceptor_loss	1.0000
6:83151881:A:AG	acceptor_gain	1.0000
6:83151881:AG:A	acceptor_gain	1.0000
6:83151881:AGGAT:A	acceptor_gain	1.0000
6:83151882:G:GG	acceptor_gain	1.0000
6:83151882:GG:G	acceptor_gain	1.0000
6:83151882:GGA:G	acceptor_gain	1.0000
6:83151882:GGAT:G	acceptor_gain	1.0000
6:83151882:GGATG:G	acceptor_gain	1.0000
6:83151967:G:GT	donor_gain	1.0000
6:83151971:T:G	donor_gain	1.0000
6:83152022:TTGA:T	donor_gain	1.0000
6:83154178:A:AG	acceptor_gain	1.0000
6:83154179:G:GA	acceptor_gain	1.0000
6:83154237:GATGA:G	donor_gain	1.0000
6:83154240:GA:G	donor_gain	1.0000
6:83154242:G:GG	donor_gain	1.0000
6:83155949:A:AG	acceptor_gain	1.0000
6:83155950:G:GG	acceptor_gain	1.0000
6:83155950:GCTC:G	acceptor_gain	1.0000

AlphaMissense

3554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:83175972:C:T	G373E	0.999
6:83175973:C:A	G373W	0.999
6:83179916:T:A	D280V	0.999
6:83175972:C:A	G373V	0.998
6:83179916:T:G	D280A	0.998
6:83179928:T:A	D276V	0.998
6:83175966:C:T	G375D	0.997
6:83175970:G:C	H374D	0.997
6:83175980:T:A	E370D	0.997
6:83175980:T:G	E370D	0.997
6:83175981:T:A	E370V	0.997
6:83179912:T:A	R281S	0.997
6:83179912:T:G	R281S	0.997
6:83179913:C:G	R281T	0.997
6:83179915:G:C	D280E	0.997
6:83179915:G:T	D280E	0.997
6:83179917:C:G	D280H	0.997
6:83179920:C:G	A279P	0.997
6:83190820:G:C	H65D	0.997
6:83175968:A:C	H374Q	0.996
6:83175968:A:T	H374Q	0.996
6:83175969:T:G	H374P	0.996
6:83175974:A:C	N372K	0.996
6:83175974:A:T	N372K	0.996
6:83179862:C:T	G298E	0.996
6:83179922:T:A	D278V	0.996
6:83179925:C:T	G277E	0.996
6:83179927:A:C	D276E	0.996
6:83179927:A:T	D276E	0.996
6:83179928:T:G	D276A	0.996

dbSNP variants (sampled 300 via entrez): RS1000012132 (6:83192683 T>C), RS1000076158 (6:83160129 G>A), RS1000253321 (6:83166621 T>C), RS1000274142 (6:83173380 G>A,C,T), RS1000325119 (6:83159495 T>C), RS1000350903 (6:83159048 A>G), RS1000433863 (6:83166499 T>C,G), RS1000512043 (6:83187370 C>A,T), RS1000604103 (6:83185653 G>A), RS1000615511 (6:83179341 C>A,T), RS1000664684 (6:83180345 G>T), RS1000684655 (6:83171625 G>T), RS1000781954 (6:83179802 C>A,G), RS1000809529 (6:83178147 TCACA>T), RS1000862665 (6:83153363 C>T)

Disease associations

OMIM: gene MIM:172100 | disease phenotypes: MIM:216920, MIM:615816, MIM:147060

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 23	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
immunodeficiency 23	Definitive	AR

Mondo (3): immunodeficiency 23 (MONDO:0014353), severe combined immunodeficiency (MONDO:0015974), hyper-IgE syndrome (MONDO:0018037)

Orphanet (3): PGM3-CDG (Orphanet:443811), Severe combined immunodeficiency (Orphanet:183660), Hyper-IgE syndrome (Orphanet:331223)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000389	Chronic otitis media
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000793	Membranoproliferative glomerulonephritis
HP:0000924	Abnormality of the skeletal system
HP:0000964	Eczematoid dermatitis
HP:0001047	Atopic dermatitis
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001290	Generalized hypotonia
HP:0001336	Myoclonus
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001581	Recurrent skin infections
HP:0001875	Decreased total neutrophil count
HP:0001878	Hemolytic anemia
HP:0001880	Increased total eosinophil count
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0001904	Autoimmune neutropenia
HP:0001999	Abnormal facial shape
HP:0002020	Gastroesophageal reflux

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C565684	Combined Inflammatory and Immunologic Defect (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Cyclosporine	increases expression	4
Valproic Acid	affects expression, decreases expression, decreases methylation	3
sodium arsenite	increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression, decreases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
fenpyroximate	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
pyrachlostrobin	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00527878	PHASE2	TERMINATED	Effect of Ranitidine on Hyper-IgE Recurrent Infection (Job’s) Syndrome
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT00260702	PHASE1	COMPLETED	Omalizumab to Treat Hyper-IgE (Job’s) Syndrome
NCT07262983	PHASE1	RECRUITING	Evaluating the Safety and Tolerability of Baricitinib in Patients With Job Syndrome With Lupus-Like Disease and/or Atopic Dermatitis
NCT01454856	Not specified	TERMINATED	Perioperative Evaluation of Immuno-inflammatory Parameters
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies