G6PC1 (glucose-6-phosphatase catalytic subunit 1)

Gene

• Entrez ID: 2538
• Gene name: Glucose-6-phosphatase catalytic subunit 1
• Gene symbol: G6PC1
• Synonyms: G6PC, G6PT, G6Pase, GSD1, GSD1a
• Chromosome: 17
• Chromosome location: 17q21.31
• Summary: Glucose-6-phosphatase (G6Pase) is a multi-subunit integral membrane protein of the endoplasmic reticulum that is composed of a catalytic subunit and transporters for G6P, inorganic phosphate, and glucose. This gene (G6PC) is one of the three glucose-6-phosphatase catalytic-subunit-encoding genes in human: G6PC, G6PC2 and G6PC3. Glucose-6-phosphatase catalyzes the hydrolysis of D-glucose 6-phosphate to D-glucose and orthophosphate and is a key enzyme in glucose homeostasis, functioning in gluconeogenesis and glycogenolysis. Mutations in this gene cause glycogen storage disease type I (GSD1). This disease, also known as von Gierke disease, is a metabolic disorder characterized by severe hypoglycemia associated with the accumulation of glycogen and fat in the liver and kidneys.[provided by RefSeq, Feb 2011]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1801175	C>T	Pathogenic	Coding sequence variant, missense variant
rs1801176	G>A	Pathogenic	Coding sequence variant, missense variant
rs80356479	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs80356482	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs80356483	G>T	Pathogenic-likely-pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant
rs80356484	G>A,T	Pathogenic-likely-pathogenic, pathogenic	Synonymous variant, coding sequence variant, 3 prime UTR variant
rs80356485	C>T	Pathogenic-likely-pathogenic	Stop gained, coding sequence variant, 3 prime UTR variant
rs80356486	TCT>-	Likely-pathogenic	Inframe deletion, coding sequence variant, 3 prime UTR variant
rs80356487	C>G,T	Pathogenic	Stop gained, missense variant, coding sequence variant, 3 prime UTR variant
rs80356488	->TA	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs104894563	C>T	Pathogenic-likely-pathogenic, pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant
rs104894565	A>G,T	Pathogenic	Missense variant, coding sequence variant
rs104894566	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs104894567	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs104894568	G>A	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs104894569	G>A,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs104894571	T>C,G	Pathogenic, uncertain-significance	Synonymous variant, missense variant, coding sequence variant
rs142917638	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained
rs143321486	C>G,T	Likely-pathogenic, uncertain-significance	3 prime UTR variant, coding sequence variant, missense variant
rs145172999	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	3 prime UTR variant, coding sequence variant, missense variant
rs199505156	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs367727229	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant
rs368450665	C>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Intron variant
rs373345919	C>T	Pathogenic	Stop gained, coding sequence variant, missense variant
rs387906505	T>A,C	Pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant
rs587776757	A>G	Pathogenic	Intron variant
rs748363083	C>A,T	Pathogenic	Coding sequence variant, stop gained, synonymous variant
rs749323139	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant, 3 prime UTR variant
rs755612674	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs756632286	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs764920787	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs775826449	T>C	Likely-pathogenic	Missense variant, synonymous variant, coding sequence variant
rs780226142	C>A,T	Pathogenic-likely-pathogenic, pathogenic	3 prime UTR variant, stop gained, synonymous variant, coding sequence variant
rs863224022	T>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant
rs863224023	G>C	Likely-pathogenic	Splice donor variant
rs1057516367	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1057516630	->T	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1057516674	GT>-	Pathogenic-likely-pathogenic	Frameshift variant, coding sequence variant
rs1057516858	G>-	Likely-pathogenic	3 prime UTR variant, frameshift variant, coding sequence variant
rs1057517008	A>C	Pathogenic-likely-pathogenic	Coding sequence variant, missense variant
rs1057517227	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1189630738	G>A,T	Likely-pathogenic	Stop gained, coding sequence variant, synonymous variant, missense variant
rs1250172816	T>G	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs1411037881	G>A	Likely-pathogenic	Splice acceptor variant
rs1457925404	G>A,C	Likely-pathogenic	Stop gained, missense variant, coding sequence variant, 3 prime UTR variant
rs1485038937	C>G	Likely-pathogenic	Stop gained, synonymous variant, coding sequence variant
rs1555558920	->TACCTCCAGGTGAATT	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1555559279	G>A	Likely-pathogenic	Splice acceptor variant
rs1555559741	C>A	Likely-pathogenic	Intron variant, stop gained, coding sequence variant
rs1555559991	C>A	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1555560140	G>A	Likely-pathogenic	Stop gained, 3 prime UTR variant, coding sequence variant
rs1555560185	->GT	Likely-pathogenic	Frameshift variant, 3 prime UTR variant, coding sequence variant
rs1567702823	G>A	Pathogenic	Stop gained, coding sequence variant
rs1567705064	ATGGTCACATCTA>-	Pathogenic	Frameshift variant, intron variant, coding sequence variant
rs1597988331	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1597989983	G>C	Likely-pathogenic	Splice donor variant
rs1597989985	T>C	Likely-pathogenic	Splice donor variant
rs1597990895	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1597990906	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1597990921	C>T	Likely-pathogenic	Missense variant, coding sequence variant, stop gained
rs1597991608	C>G	Pathogenic	Intron variant
rs1597991733	C>A	Likely-pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006281	hsa-miR-23a-3p	Luciferase reporter assay	22318941
MIRT054921	hsa-miR-33b-5p	Luciferase reporter assay, qRT-PCR	23716591
MIRT461650	hsa-miR-4309	PAR-CLIP	23592263
MIRT461651	hsa-miR-3198	PAR-CLIP	23592263
MIRT461652	hsa-miR-106a-3p	PAR-CLIP	23592263
MIRT461653	hsa-miR-3650	PAR-CLIP	23592263
MIRT461654	hsa-miR-122-5p	PAR-CLIP	23592263
MIRT461655	hsa-miR-504-3p	PAR-CLIP	23592263
MIRT461656	hsa-miR-4726-3p	PAR-CLIP	23592263
MIRT461657	hsa-miR-1298-3p	PAR-CLIP	23592263
MIRT461658	hsa-miR-454-3p	PAR-CLIP	23592263
MIRT461659	hsa-miR-3666	PAR-CLIP	23592263
MIRT461660	hsa-miR-4295	PAR-CLIP	23592263
MIRT461661	hsa-miR-301b-3p	PAR-CLIP	23592263
MIRT461662	hsa-miR-301a-3p	PAR-CLIP	23592263
MIRT461663	hsa-miR-130b-3p	PAR-CLIP	23592263
MIRT461664	hsa-miR-130a-3p	PAR-CLIP	23592263
MIRT496505	hsa-miR-19a-3p	PAR-CLIP	22291592
MIRT496506	hsa-miR-3189-5p	PAR-CLIP	22291592
MIRT496507	hsa-miR-4758-3p	PAR-CLIP	22291592
MIRT496508	hsa-miR-5699-5p	PAR-CLIP	22291592
MIRT496509	hsa-miR-203a-3p	PAR-CLIP	22291592
MIRT496510	hsa-miR-4762-5p	PAR-CLIP	22291592
MIRT496511	hsa-miR-365b-3p	PAR-CLIP	22291592
MIRT496512	hsa-miR-365a-3p	PAR-CLIP	22291592
MIRT532113	hsa-miR-539-3p	PAR-CLIP	22012620
MIRT532114	hsa-miR-485-3p	PAR-CLIP	22012620
MIRT532115	hsa-miR-4536-5p	PAR-CLIP	22012620
MIRT532116	hsa-miR-664a-3p	PAR-CLIP	22012620
MIRT532117	hsa-miR-6074	PAR-CLIP	22012620
MIRT532118	hsa-miR-3163	PAR-CLIP	22012620
MIRT532119	hsa-miR-577	PAR-CLIP	22012620
MIRT532120	hsa-miR-5692a	PAR-CLIP	22012620
MIRT532121	hsa-miR-3662	PAR-CLIP	22012620
MIRT532122	hsa-miR-4668-5p	PAR-CLIP	22012620
MIRT532123	hsa-miR-1253	PAR-CLIP	22012620
MIRT532124	hsa-miR-4311	PAR-CLIP	22012620
MIRT574248	hsa-miR-574-5p	PAR-CLIP	20371350
MIRT574249	hsa-miR-6821-5p	PAR-CLIP	20371350
MIRT574250	hsa-miR-6867-5p	PAR-CLIP	20371350
MIRT574251	hsa-miR-223-5p	PAR-CLIP	20371350
MIRT574252	hsa-miR-4793-5p	PAR-CLIP	20371350
MIRT574253	hsa-miR-5196-3p	PAR-CLIP	20371350
MIRT574254	hsa-miR-136-3p	PAR-CLIP	20371350
MIRT650121	hsa-miR-514b-5p	HITS-CLIP	23824327
MIRT650122	hsa-miR-513c-5p	HITS-CLIP	23824327
MIRT650123	hsa-miR-4284	HITS-CLIP	23824327
MIRT650124	hsa-miR-4772-3p	HITS-CLIP	23824327
MIRT650125	hsa-miR-4638-5p	HITS-CLIP	23824327
MIRT650126	hsa-miR-1307-3p	HITS-CLIP	23824327
MIRT650127	hsa-miR-1304-3p	HITS-CLIP	23824327
MIRT650128	hsa-miR-6741-3p	HITS-CLIP	23824327
MIRT650129	hsa-miR-6890-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004346	Function	Glucose-6-phosphatase activity	EXP	12093795
GO:0004346	Function	Glucose-6-phosphatase activity	IBA	21873635
GO:0004346	Function	Glucose-6-phosphatase activity	IDA	8211187, 10318794, 15661744
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005977	Process	Glycogen metabolic process	TAS	8211187
GO:0005980	Process	Glycogen catabolic process	IEA
GO:0006094	Process	Gluconeogenesis	IBA	21873635
GO:0006094	Process	Gluconeogenesis	IEA
GO:0006094	Process	Gluconeogenesis	IMP	8211187
GO:0006094	Process	Gluconeogenesis	TAS
GO:0006641	Process	Triglyceride metabolic process	IEA
GO:0008202	Process	Steroid metabolic process	IEA
GO:0009743	Process	Response to carbohydrate	IEA
GO:0010468	Process	Regulation of gene expression	IEA
GO:0015760	Process	Glucose-6-phosphate transport	IEA
GO:0016020	Component	Membrane	IBA	21873635
GO:0016021	Component	Integral component of membrane	IDA	10318794
GO:0016773	Function	Phosphotransferase activity, alcohol group as acceptor	IEA
GO:0030176	Component	Integral component of endoplasmic reticulum membrane	TAS	10318794
GO:0032094	Process	Response to food	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0042301	Function	Phosphate ion binding	IMP	12093795
GO:0042593	Process	Glucose homeostasis	IMP	8211187
GO:0042632	Process	Cholesterol homeostasis	IEA
GO:0046415	Process	Urate metabolic process	IEA
GO:0046838	Process	Phosphorylated carbohydrate dephosphorylation	IEA
GO:0051156	Process	Glucose 6-phosphate metabolic process	IBA	21873635
GO:1904638	Process	Response to resveratrol	IEA

Other IDs

• MIM: 613742
• HGNC: 4056
• e!Ensembl: ENSG00000131482

Protein

• UniProt ID: P35575
• Protein name: Glucose-6-phosphatase catalytic subunit 1 (EC 3.1.3.9) (Glucose-6-phosphatase) (G-6-Pase) (G6Pase) (Glucose-6-phosphatase alpha) (G6Pase-alpha)
• Protein 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 in the terminal step of glycogenolysis and gluconeogenesis. Hence, it is the key enzyme in homeostatic regulation of blood glucose levels.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01569	PAP2	57 → 204	PAP2 superfamily	Family

• Sequence:

  MEEGMNVLHDFGIQSTHYLQVNYQDSQDWFILVSVIADLRNAFYVLFPIWFHLQEAVGIK
  LLWVAVIGDWLNLVFKWILFGQRPYWWVLDTDYYSNTSVPLIKQFPVTCETGPGSPSGHA
  MGTAGVYYVMVTSTLSIFQGKIKPTYRFRCLNVILWLGFWAVQLNVCLSRIYLAAHFPHQ
  VVAGVLSGIAVAETFSHIHSIYNASLKKYFLITFFLFSFAIGFYLLLKGLGVDLLWTLEK
  AQRWCEQPEWVHIDTTPFASLLKNLGTLFGLGLALNSSMYRESCKGKLSKWLPFRLSSIV
  ASLVLLHVFDSLKPPSQVELVFYVLSFCKSAVVPLASVSVIPYCLAQVLGQPHKKSL

• Sequence length: 357

Pathways

KEGG:

Glycolysis / Gluconeogenesis
Galactose metabolism
Starch and sucrose metabolism
Metabolic pathways
FoxO signaling pathway
PI3K-Akt signaling pathway
AMPK signaling pathway
Insulin signaling pathway
Adipocytokine signaling pathway
Glucagon signaling pathway
Insulin resistance
Carbohydrate digestion and absorption

Reactome:

Glycogen storage disease type Ia (G6PC)
Gluconeogenesis

Associated diseases

Disease name	Disease term	References
	Anemia
	Malignant neoplasm of breast
	Dwarfism
	Eyelid Xanthoma
	Focal glomerulosclerosis
	Glycogen Storage Disease	27604308, 15316959, 8211187
	Glycogen Storage Disease Type I	10960498, 10070617, 10447271, 7623438, 8733042, 12373566, 10094563, 7655466, 10738005, 10612834, 15316959, 27604308, 9700612, 11058903, 15151508, 7573034, 8182131, 11058910, 10874313, 9332655, 15542400, 10748407, 8211187, 9001800, 9506659, 9700613
	Glycogen storage disease type Ia	25308557, 15542400, 11739393, 10960498, 28397058, 10447271, 10748407, 17994282, 8734807, 21599942, 23046672, 7744838, 10070617, 19762333, 10234610, 22899091, 25333069, 8211187, 24385852, 10612834, 7573034, 10944847, 23352793, 19541498, 23486339, 24565827, 21983240, 18449899, 11596659, 10874313, 7623438, 7525963, 18008183, 15316959, 28659124, 7668282, 9705299, 11949931, 24082139, 23000067, 10834516, 8733042, 12373566, 8182131, 10094563, 9332655, 12093795, 15455297, 23312056, 9001800, 10738525, 28360385, 16435186, 7814621, 7655466, 9630072, 10797430, 11386847, 10604148, 11058903, 24980439, 11161844, 11310582, 9359038, 11916325, 18083610
	Glycogen storage disease due to glucose-6-phosphatase deficiency type Ia
	Gout
	Hyperlipidemia
	Hypertensive disease
	Hyperuricemia
	Hypoglycemia
	Lipidemia retinalis
	Liver carcinoma
	Nephrolithiasis
	Osteoporosis
	Pancreatitis
	Xanthoma
	Xanthomatosis