G6PC1

glucose-6-phosphatase catalytic subunit 1, the group of Glucose 6-phosphatases, catalytic

Basic information

Region (hg38): 17:42900796-42914438

Previous symbols: [ "G6PT", "G6PC" ]

Links

ENSG00000131482 ∙ NCBI:2538 ∙ OMIM:613742 ∙ HGNC:4056 ∙ Uniprot:P35575 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to glucose-6-phosphatase deficiency type IA (Definitive), mode of inheritance: AR
• glycogen storage disease due to glucose-6-phosphatase deficiency type IA (Strong), mode of inheritance: AR
• glycogen storage disease due to glucose-6-phosphatase deficiency type IA (Strong), mode of inheritance: AR
• glycogen storage disease due to glucose-6-phosphatase deficiency type IA (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease Ia	AR	Biochemical; Gastrointestinal; Oncologic; Renal	Dietary measures (eg, with Glycosade or cornstarch) can be beneficial to allow optimal glucose levels and promote growth and development (additionally, specific carbohydrate sources should be limited); Allopurinol to prevent gout and lipid-lowering medications to prevent hyperlipidemia may be necessary when dietary therapy is ineffective; Citrate supplementation and ACE inhibitors may help prevent development of decrease renal complications, though renal transplant may ultimately be necessary; Surveillance for and treatment of hepatic neoplasms (including liver transplant in some) can be beneficial	Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic; Renal	5240134; 4302545; 204806; 204758; 6928317; 6581385; 2883397; 3030527; 3422104; 2199830; 2109144; 1743219; 8391447; 8211187; 8448918; 8319728; 8441093; 8319729; 8319726 ; 8203427; 8273986; 7668282; 7573034; 8733042; 8758135; 9427147; 9332655; 10472532; 10070617; 10748407; 11241046; 11757580; 15151508; 19762333; 20301489; 20720360; 21058447; 21481415; 21620082; 29223626

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the G6PC1 gene.

• Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (460 variants)
• not provided (46 variants)
• Inborn genetic diseases (31 variants)
• not specified (23 variants)
• Glycogen storage disease, type I (7 variants)
• G6PC1-related condition (4 variants)
• Glycogen storage disease (2 variants)
• Hypoglycemia;Short stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the G6PC1 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		1	3	124	1	129
missense	23	33	83	1	1	141
nonsense	19	13	1			33
start loss						0
frameshift	16	12				28
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)	1	5				6
splice region		1	3	14		18
non coding			52	21	23	96
Total	59	66	142	146	25

Highest pathogenic variant AF is 0.000348

Variants in G6PC1

This is a list of pathogenic ClinVar variants found in the G6PC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-42900800-G-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA • G6PC1-related disorder	Benign/Likely benign (Nov 27, 2023)
17-42900832-G-A		not specified • Glycogen storage disease due to glucose-6-phosphatase deficiency type IA • G6PC1-related disorder	Conflicting classifications of pathogenicity (May 18, 2022)
17-42900882-GG-AA		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Uncertain significance (Jun 26, 2022)
17-42900885-A-G		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Apr 22, 2021)
17-42900890-T-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely pathogenic (Apr 21, 2022)
17-42900890-T-G		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Conflicting classifications of pathogenicity (Jan 12, 2024)
17-42900891-G-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely pathogenic (Jun 27, 2023)
17-42900891-G-C		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely pathogenic (Dec 11, 2023)
17-42900891-G-T		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely pathogenic (Sep 03, 2022)
17-42900894-T-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Uncertain significance (Jan 18, 2022)
17-42900894-T-C		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Conflicting classifications of pathogenicity (Jan 03, 2024)
17-42900903-T-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA • not specified	Uncertain significance (Sep 16, 2021)
17-42900918-G-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Dec 13, 2021)
17-42900921-A-C		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Jan 20, 2021)
17-42900921-A-G		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Dec 30, 2019)
17-42900922-A-G		not specified	Uncertain significance (Jan 20, 2023)
17-42900923-C-G		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Uncertain significance (Oct 18, 2017)
17-42900924-A-C		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Sep 12, 2023)
17-42900926-A-ATTACCTCCAGGTGAAT		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely pathogenic (Oct 10, 2017)
17-42900930-C-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Pathogenic (Aug 14, 2021)
17-42900933-C-T		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Nov 09, 2023)
17-42900935-A-G		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Conflicting classifications of pathogenicity (Mar 25, 2024)
17-42900935-AG-A		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely pathogenic (-)
17-42900942-T-C		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Likely benign (Nov 30, 2022)
17-42900945-C-G		Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Pathogenic (Dec 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
G6PC1	protein_coding	protein_coding	ENST00000253801	5	12573

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000184	0.895	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.266	182	192	0.946	0.0000109	2330
Missense in Polyphen		65	71.82	0.90504		882
Synonymous	-1.58	100	81.8	1.22	0.00000520	715
Loss of Function	1.54	10	16.8	0.596	8.34e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000842	0.000842
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000281	0.000281
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. Forms with the glucose-6-phosphate transporter (SLC37A4/G6PT) the complex responsible for glucose production through glycogenolysis and gluconeogenesis. Hence, it is the key enzyme in homeostatic regulation of blood glucose levels.
• Disease: DISEASE: Glycogen storage disease 1A (GSD1A) [MIM:232200]: A metabolic disorder characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Patients manifest a wide range of clinical symptoms and biochemical abnormalities, including hypoglycemia, severe hepatomegaly due to excessive accumulation of glycogen, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. {ECO:0000269|PubMed:10070617, ECO:0000269|PubMed:10094563, ECO:0000269|PubMed:10447271, ECO:0000269|PubMed:10612834, ECO:0000269|PubMed:10738005, ECO:0000269|PubMed:10748407, ECO:0000269|PubMed:10874313, ECO:0000269|PubMed:10960498, ECO:0000269|PubMed:11058903, ECO:0000269|PubMed:11058910, ECO:0000269|PubMed:12373566, ECO:0000269|PubMed:15151508, ECO:0000269|PubMed:15316959, ECO:0000269|PubMed:15542400, ECO:0000269|PubMed:7573034, ECO:0000269|PubMed:7623438, ECO:0000269|PubMed:7655466, ECO:0000269|PubMed:8182131, ECO:0000269|PubMed:8733042, ECO:0000269|PubMed:9001800, ECO:0000269|PubMed:9332655, ECO:0000269|PubMed:9506659, ECO:0000269|PubMed:9700612, ECO:0000269|PubMed:9700613}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Starch and sucrose metabolism - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Glycolysis;Galactose Metabolism;Glycogenosis, Type VII. Tarui disease;Gluconeogenesis;Glycogenosis, Type IA. Von gierke disease;GLUT-1 deficiency syndrome;Glycogenosis, Type IC;Fanconi-bickel syndrome;Congenital disorder of glycosylation CDG-IId;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Lactose Synthesis;Galactosemia;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Angiopoietin Like Protein 8 Regulatory Pathway;PI3K-Akt Signaling Pathway;Glycolysis and Gluconeogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;DNA Damage Response (only ATM dependent);Metabolism of carbohydrates;glycogenolysis;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Metabolism;gluconeogenesis;Gluconeogenesis;Glucose metabolism;FoxO family signaling;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.795

Intolerance Scores

• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.893
• hipred: N
• hipred_score: 0.471
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: G6pc
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; neoplasm; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: glycogen metabolic process;glycogen catabolic process;gluconeogenesis;triglyceride metabolic process;steroid metabolic process;regulation of gene expression;glucose-6-phosphate transport;response to food;multicellular organism growth;glucose homeostasis;cholesterol homeostasis;urate metabolic process;phosphorylated carbohydrate dephosphorylation;glucose 6-phosphate metabolic process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;integral component of endoplasmic reticulum membrane
• Molecular function: glucose-6-phosphatase activity;phosphotransferase activity, alcohol group as acceptor;phosphate ion binding