G6PC2

Summary

G6PC2 (glucose-6-phosphatase catalytic subunit 2, HGNC:28906) is a protein-coding gene on chromosome 2q31.1, encoding Glucose-6-phosphatase 2 (Q9NQR9). May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum.

This gene encodes an enzyme belonging to the glucose-6-phosphatase catalytic subunit family. These enzymes are part of a multicomponent integral membrane system that catalyzes the hydrolysis of glucose-6-phosphate, the terminal step in gluconeogenic and glycogenolytic pathways, allowing the release of glucose into the bloodstream. The family member encoded by this gene is found in pancreatic islets and does not exhibit phosphohydrolase activity, but it is a major target of cell-mediated autoimmunity in diabetes. Several alternatively spliced transcript variants of this gene have been described, but their biological validity has not been determined.

Source: NCBI Gene 57818 — RefSeq curated summary.

At a glance

• GWAS associations: 44
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_021176

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28906
Approved symbol	G6PC2
Name	glucose-6-phosphatase catalytic subunit 2
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	IGRP
Ensembl gene	ENSG00000152254
Ensembl biotype	protein_coding
OMIM	608058
Entrez	57818

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000282075, ENST00000375363, ENST00000421979, ENST00000429379, ENST00000461586

RefSeq mRNA: 2 — MANE Select: NM_021176 NM_001081686, NM_021176

CCDS: CCDS2230, CCDS46443

Canonical transcript exons

ENST00000375363 — 5 exons

Exon	Start	End
ENSE00001926620	168907568	168910000
ENSE00001951620	168901291	168901549
ENSE00002516305	168902445	168902554
ENSE00003522916	168904505	168904616
ENSE00003537996	168906664	168906779

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 99.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0436 / max 21.6347, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23519	0.0436	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.18	gold quality
pancreas	UBERON:0001264	88.33	gold quality
body of pancreas	UBERON:0001150	83.93	gold quality
duodenum	UBERON:0002114	50.53	gold quality
left testis	UBERON:0004533	46.88	gold quality
testis	UBERON:0000473	46.86	gold quality
right testis	UBERON:0004534	45.30	gold quality
metanephros cortex	UBERON:0010533	42.90	gold quality
calcaneal tendon	UBERON:0003701	42.77	silver quality
hindlimb stylopod muscle	UBERON:0004252	42.25	gold quality
granulocyte	CL:0000094	42.22	silver quality
colonic epithelium	UBERON:0000397	41.65	gold quality
skeletal muscle tissue	UBERON:0001134	41.43	gold quality
leukocyte	CL:0000738	41.16	silver quality
monocyte	CL:0000576	41.07	silver quality
liver	UBERON:0002107	40.93	silver quality
ventricular zone	UBERON:0003053	39.96	gold quality
right lobe of liver	UBERON:0001114	39.95	gold quality
body of stomach	UBERON:0001161	39.08	gold quality
prefrontal cortex	UBERON:0000451	39.07	gold quality
adrenal tissue	UBERON:0018303	38.57	silver quality
stomach	UBERON:0000945	38.51	gold quality
Ammon’s horn	UBERON:0001954	38.34	gold quality
cortex of kidney	UBERON:0001225	38.19	gold quality
tonsil	UBERON:0002372	38.17	gold quality
right coronary artery	UBERON:0001625	37.89	silver quality
primary visual cortex	UBERON:0002436	37.31	silver quality
superior frontal gyrus	UBERON:0002661	37.27	silver quality
lower esophagus mucosa	UBERON:0035834	37.26	gold quality
ganglionic eminence	UBERON:0004023	37.18	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	7203.56
E-GEOD-83139	yes	5601.02
E-MTAB-5061	yes	2674.88
E-GEOD-81608	yes	2416.81
E-ENAD-27	yes	1452.08
E-ANND-3	no	2.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA1, FOXA2, FOXC1, GATA3, MAF, MAFA, MYOD1, NEUROD1, PAX6, PDX1, PITX2, USF1

miRNA regulators (miRDB)

89 targeting G6PC2, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6751-5P	99.56	64.99	1145

Literature-anchored findings (GeneRIF, showing 40)

• IGRP is likely the authentic islet-specific glucose-6-phosphatase catalytic subunit, and selective inhibitors to this molecule can be obtained (PMID:14722102)
• Data show that islet-specific glucose-6-phosphatase-related protein is an endoplasmic reticulum membrane glycoprotein, and is degraded through the proteasome pathway that generates the major histocompatibility complex class I-presented peptides. (PMID:15044018)
• Alpha mutants containing the beta cell antigen sequence are preferentially degraded in cells, which prevents targeting by pathogenic CD8+ T cells implying that IGRP levels in beta cells could dictate susceptibilities to diabetes. (PMID:16012821)
• This study demonstrates the prevalence of CD4+ IGRP-specific T cells not only in subjects with type I diabetes, but also in healthy individuals carrying the DR0301 or DR0401 haplotypes. (PMID:16493034)
• Differential tissue expression may aid in designing synthetic peptides for the identification of IGRP-specific autoreactive T cells in patients with type 1 diabetes. (PMID:16520917)
• human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species. (PMID:17376840)
• missense mutation in exon 4, L173P, found in glycogen storage disease type Ia (PMID:17607665)
• SNP rs560887 was associated with fasting plasma glucose (FPG); it is speculated that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells (PMID:18451265)
• Genetic Polymorphisms of the G6PC2 gene may underlie variation in fasting blood glucose levels, and genetic Polymorphisms of the ABCB11 gene may also contribute to such variation. (PMID:18521185)
• Data suggest that a group of transcription factors, including MafA and Foxa2, regulate expression of two major autoantigens in type 1 diabetes, including islet-specific glucose-6-phosphatase catalytic subunit-related protein. (PMID:18753309)
• rs573225 is a functional cis-regulatory (epi)-single-nucleotide polymorphism (SNP) of G6PC2 associated with glucose-insulin homeostasis in obese children, likely to explain the results of recent genome-wide association studies in nondiabetic adults. (PMID:18984742)
• SNP rs16856187 was associated with type 2 diabetes and fasting plasma glucose in the Chinese population; carriers of the A allele displayed a higher risk for type 2 diabetes and a lower fasting plasma glucose level in the controls. (PMID:19082990)
• Mutations and single nucleotide polymorphisms in this protein do not conribute to neonatal or early infant type 1 diabetes. (PMID:19238352)
• Variations and single-nucleotide polymorphisms are associated in variations in fasting plasma glucose and an increased risk of type 2 diabetes. (PMID:19533084)
• The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate. (PMID:19669124)
• Data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion. (PMID:19741163)
• Fasting glucose association at G6PC2 is replicable across ethnic groups, although ethnic diversity in the pattern and strength of linkage disequilibrium exists. (PMID:19937311)
• results independently confirm the robust association of glucose-6-phosphatase catalytic 2(G6PC2)/rs560887 with fasting plasma glucose levels in non-diabetic non-Hispanic white Americans (PMID:20029179)
• Potential role linking single nucleotide polymphism in G6PC2 to variations in fasting blood glucose. (PMID:20622168)
• Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. (PMID:20628598)
• Study showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. (PMID:20668700)
• The effects of hyperglycemia on insulin secretion override the more subtle effects of genetic variation in the G6PC2 locus on insulin secretion. (PMID:20826583)
• Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced beta-cell function, as indicated by homeostasis model assessment of beta-cell function. (PMID:21515849)
• A single nucleotide polymorphism in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes. (PMID:22438186)
• Variation at the rs560887 locus of G6PC2 is associated with worse glycated haemoglobin levels in individuals with GCK mutations; GG homozygotes are more likely to meet diagnostic criteria for diabetes based on HbA(1c) level. (PMID:22486180)
• one of the newly identified spontaneously reactive epitopes (P8 [IGRP(55-72)]) is highly conserved between mice and man, suggesting that it might also be a target of HLA-DQ8-restricted T cells in diabetic human subjects (PMID:22983906)
• polymorphisms in the G6PC2 gene contribute to the association with higher fasting plasma glucose levels (PMID:23508304)
• GCKR rs780094 variant confers high cross-ethnicity risk for the development of T2DM, while significant associations between GCK, MTNR1B and G6PC2 variants and T2DM risk are limited to Caucasians. (PMID:23840762)
• three novel G6PC2 variants were discovered that occur in islets only, leading to protein truncations, frame shifts and neo-sequences prone to immunogenicity. (PMID:24030068)
• rs560887 associated with increased fasting glucose levels (PMID:25078492)
• we identified coding variants at several GWAS loci which point to the genes underlying these association signals. Importantly, we found that multiple coding variants in G6PC2 result in a loss of protein function and lower fasting glucose levels. (PMID:25625282)
• Data suggest that islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP)-specific CD4(+) helper T (Th) cells play a unique pathogenic role in adult-onset T1D (AT1D). (PMID:26341315)
• these studies identify multiple G6PC2 variants that have the potential to be associated with altered FBG in humans. (PMID:27611587)
• All three allele variants of G6PC2 (rs560887, rs16856187 and rs573225) are associated with elevated fasting glucose, with two variants (rs560887 in the Caucasians subgroup and rs16856187 under the allele and dominant model) being associated with T2 diabetes as well.[meta-analysis] (PMID:28704540)
• The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance, whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance. (PMID:28783164)
• The results suggest that the GCKR and G6PC2 genes may contribute to the risk of type 2 diabetes independently and/or in an interactive manner in the Han Chinese population. (PMID:30055620)
• Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose. (PMID:32213654)
• Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose. (PMID:33842983)
• Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11). (PMID:34128214)
• G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo. (PMID:35277194)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	G6pc2	ENSMUSG00000005232
rattus_norvegicus	AABR07052465.1	ENSRNOG00000050620
drosophila_melanogaster	G6P	FBGN0031463

Paralogs (2): G6PC1 (ENSG00000131482), G6PC3 (ENSG00000141349)

Protein

Protein identifiers

Glucose-6-phosphatase 2 — Q9NQR9 (reviewed: Q9NQR9)

Alternative names: Islet-specific glucose-6-phosphatase catalytic subunit-related protein

All UniProt accessions (2): Q9NQR9, C9IYU7

UniProt curated annotations — full annotation on UniProt →

Function. May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Specifically expressed in pancreas and also detected to a lower extent in testis. Expressed by most islet cells in the pancreas (at protein level).

Post-translational modifications. N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome.

Pathway. Carbohydrate biosynthesis; gluconeogenesis.

Polymorphism. Genetic variations in G6PC2 define the fasting plasma glucose levels quantitative trait locus 1 (FGQTL1) [MIM:612108]. The normal fasting plasma glucose level in the plasma is defined as less than 100 mg per deciliter (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality.

Similarity. Belongs to the glucose-6-phosphatase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQR9-1	1	yes
Q9NQR9-2	2
Q9NQR9-3	3

RefSeq proteins (2): NP_001075155, NP_066999* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR016275	Glucose-6-phosphatase	Family
IPR036938	PAP2/HPO_sf	Homologous_superfamily

Pfam: PF01569

Enzyme classification (BRENDA):

• EC 3.1.3.9 — glucose-6-phosphatase (BRENDA: 75 organisms, 95 substrates, 121 inhibitors, 58 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-GLUCOSE 6-PHOSPHATE	0.1–5.3	30
CARBAMOYL PHOSPHATE	0.6–2.5	6
GLUCOSE 6-PHOSPHATE	0.51–2.7	6
DIPHOSPHATE	1.3–1.8	2
ADP	11.1	1
ATP	4.7	1
CDP	3.8	1
CTP	3.1	1
DCTP	2.6	1
GDP	2.7	1
GTP	3.6	1
ITP	6.1	1
PHOSPHOENOLPYRUVATE	6.9	1
PHOSPHORAMIDE	2.8	1

Catalyzed reactions (Rhea), 1 shown:

• D-glucose 6-phosphate + H2O = D-glucose + phosphate (RHEA:16689)

UniProt features (39 total): topological domain 10, transmembrane region 9, sequence variant 6, splice variant 4, mutagenesis site 3, active site 2, binding site 2, chain 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQR9-F1	89.91	0.69

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 (2): 115 (proton donor); 174 (nucleophile)

Ligand- & substrate-binding residues (2): 79; 168

Glycosylation sites (1): 92

Mutagenesis-validated functional residues (3):

Position	Phenotype
50	no effect on n-glycosylation.
92	loss of n-glycosylation.
287	no effect on n-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70263	Gluconeogenesis

MSigDB gene sets: 129 (showing top): KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_GLUCOSE_6_PHOSPHATE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_SECRETION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (4): gluconeogenesis (GO:0006094), glucose homeostasis (GO:0042593), regulation of insulin secretion (GO:0050796), glucose 6-phosphate metabolic process (GO:0051156)

GO Molecular Function (2): glucose-6-phosphatase activity (GO:0004346), hydrolase activity (GO:0016787)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glucose metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glucose metabolic process	1
hexose biosynthetic process	1
carbohydrate homeostasis	1
insulin secretion	1
regulation of protein secretion	1
regulation of peptide hormone secretion	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
sugar-terminal-phosphatase activity	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
G6PC2	INS	P01308	898
G6PC2	GCK	P35557	894
G6PC2	GCG	P01275	832
G6PC2	SLC37A4	O43826	825
G6PC2	SLC2A2	P11168	818
G6PC2	PCK1	P35558	802
G6PC2	MTNR1B	P49286	800
G6PC2	ADCY5	O95622	793
G6PC2	AGL	P35573	788
G6PC2	PYGL	P06737	782
G6PC2	PYGB	P11216	782
G6PC2	PYGM	P11217	781
G6PC2	PCK2	Q16822	758
G6PC2	DGKB	Q9Y6T7	757
G6PC2	CD8A	P01732	731
G6PC2	PC	P11498	731

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ECE1	G6PC2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): G6PC2 (Cross-Linking-MS (XL-MS)), G6PC2 (Cross-Linking-MS (XL-MS)), G6PC2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0AAS4, A0JP80, A4II83, A5D6W6, A7YWN2, B2MVP8, D4AD75, O04928, O42153, O42154, O49639, O64761, O70536, P0CW70, P23501, P47013, P53223, P53439, Q06676, Q0VFE3, Q1LW89, Q1LZA4, Q20696, Q20735, Q52KL1, Q568I2, Q5CZ37, Q5CZN0, Q68EV0, Q6AX73, Q6NUT2, Q7K0P4, Q7T3T4, Q7TN73, Q7TSN4, Q7TSX5, Q7Z7B1, Q810K3, Q86IX2, Q86VZ5

Diamond homologs: A1A5Z0, O19133, O42153, O42154, P35575, P35576, P43428, Q148G2, Q19KA1, Q29RU6, Q6AZ83, Q6NSQ9, Q9BUM1, Q9NQR9, Q9Z186

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
G6PC2	“up-regulates quantity”	α-D-glucose	“chemical modification”
G6PC2	“down-regulates quantity”	“alpha-D-glucose 6-phosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

815 predictions. Top by Δscore:

Variant	Effect	Δscore
2:168901439:G:GT	donor_gain	0.9900
2:168901440:A:T	donor_gain	0.9700
2:168907665:A:AG	acceptor_gain	0.9600
2:168907666:G:GG	acceptor_gain	0.9600
2:168907666:GTT:G	acceptor_gain	0.9600
2:168901383:GAC:G	donor_gain	0.9500
2:168906779:G:GA	donor_gain	0.9400
2:168901511:AGC:A	donor_gain	0.9300
2:168907665:AGTT:A	acceptor_gain	0.9200
2:168907666:GTTG:G	acceptor_gain	0.9200
2:168906881:G:C	acceptor_gain	0.8500
2:168901510:T:TA	donor_gain	0.8400
2:168901545:AAATG:A	donor_loss	0.8400
2:168901547:ATGG:A	donor_loss	0.8400
2:168901548:TGGTA:T	donor_loss	0.8400
2:168901550:G:GA	donor_loss	0.8400
2:168901551:T:A	donor_loss	0.8400
2:168901350:A:T	donor_gain	0.8200
2:168901552:A:C	donor_loss	0.8100
2:168901349:G:GT	donor_gain	0.8000
2:168902928:G:T	acceptor_gain	0.8000
2:168904591:GA:G	donor_gain	0.8000
2:168906784:A:G	donor_gain	0.8000
2:168902927:A:T	acceptor_gain	0.7900
2:168901833:TTC:T	donor_gain	0.7800
2:168901393:C:G	donor_gain	0.7400
2:168902812:A:AG	acceptor_gain	0.7300
2:168902813:G:GG	acceptor_gain	0.7300
2:168902924:CAAA:C	acceptor_gain	0.7100
2:168902925:AAAG:A	acceptor_gain	0.7100

AlphaMissense

2348 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:168901547:A:C	K72N	0.991
2:168901547:A:T	K72N	0.991
2:168906746:T:C	F175L	0.990
2:168906748:T:A	F175L	0.990
2:168906748:T:G	F175L	0.990
2:168901546:A:T	K72I	0.989
2:168901548:T:A	W73R	0.984
2:168901548:T:C	W73R	0.984
2:168904507:A:C	S111R	0.983
2:168904509:T:A	S111R	0.983
2:168904509:T:G	S111R	0.983
2:168906747:T:G	F175C	0.982
2:168901535:T:A	N68K	0.975
2:168901535:T:G	N68K	0.975
2:168906747:T:C	F175S	0.975
2:168901527:T:A	W66R	0.974
2:168901527:T:C	W66R	0.974
2:168902472:G:C	W82C	0.974
2:168902472:G:T	W82C	0.974
2:168906743:C:G	H174D	0.974
2:168906767:G:A	G182R	0.974
2:168906767:G:C	G182R	0.974
2:168901545:A:G	K72E	0.972
2:168902465:C:A	P80H	0.972
2:168904543:T:A	W123R	0.970
2:168904543:T:C	W123R	0.970
2:168902461:C:G	R79G	0.969
2:168902462:G:C	R79P	0.969
2:168904511:C:A	P112Q	0.969
2:168906716:T:C	C165R	0.969

dbSNP variants (sampled 300 via entrez): RS1000177745 (2:168903618 G>C), RS1000613134 (2:168903835 G>T), RS1001309528 (2:168900177 A>G), RS1001384850 (2:168903597 A>G), RS1001614628 (2:168904064 G>A,C), RS1001752542 (2:168903838 T>C,G), RS1001887616 (2:168905490 C>T), RS1002255128 (2:168904925 A>T), RS1002543896 (2:168908467 C>T), RS1002979546 (2:168901739 T>C,G), RS1003517735 (2:168900819 C>T), RS1003550287 (2:168900471 T>C), RS1003621578 (2:168899859 T>A), RS1005319332 (2:168906454 T>C), RS1005506632 (2:168899408 C>A,T)

Disease associations

OMIM: gene MIM:608058 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST000202_1	Fasting plasma glucose	4.000000e-07
GCST000205_1	Fasting plasma glucose	4.000000e-23
GCST000276_2	Fasting plasma glucose	1.000000e-57
GCST000292_5	Metabolic traits	6.000000e-10
GCST000303_3	Glycated hemoglobin levels	5.000000e-10
GCST000568_1	Fasting blood glucose	9.000000e-218
GCST000803_2	Glycated hemoglobin levels	8.000000e-18
GCST001391_9	Metabolite levels	2.000000e-17
GCST001436_12	Metabolic syndrome	5.000000e-26
GCST001486_3	Fasting plasma glucose	2.000000e-06
GCST001527_14	Fasting blood glucose (BMI interaction)	2.000000e-113
GCST001639_17	Metabolite levels	4.000000e-15
GCST002110_5	Glycemic traits (pregnancy)	2.000000e-16
GCST002303_1	Glycated hemoglobin levels	1.000000e-17
GCST002390_9	Glycated hemoglobin levels	3.000000e-11
GCST002586_6	Fasting plasma glucose	2.000000e-36
GCST003433_5	Serum lycopene concentrations	1.000000e-06
GCST004206_1	Fasting plasma glucose	6.000000e-68
GCST004206_10	Fasting plasma glucose	2.000000e-75
GCST005145_6	Glycated hemoglobin levels	4.000000e-06
GCST005180_6	Homeostasis model assessment of beta-cell function	2.000000e-66
GCST005186_16	Fasting blood glucose	3.000000e-99
GCST005913_2	Fasting blood glucose	4.000000e-08
GCST005913_4	Fasting blood glucose	7.000000e-12
GCST005913_5	Fasting blood glucose	2.000000e-09
GCST006001_8	Hemoglobin A1c levels	1.000000e-11
GCST006002_4	Blood sugar levels	3.000000e-37
GCST006060_2	Hemoglobin A1c levels	3.000000e-07
GCST006629_82	Pulse pressure	4.000000e-19
GCST006993_3	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-06

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004468	glucose measurement
EFO:0004541	HbA1c measurement
EFO:0004725	metabolite measurement
EFO:0000195	metabolic syndrome
EFO:0004340	body mass index
EFO:0004723	coronary artery calcification
EFO:0007801	lycopene measurement
EFO:0004469	HOMA-B
EFO:0007629	hemoglobin A1 measurement
EFO:0005763	pulse pressure measurement
EFO:0005035	hippocampal volume
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004467	insulin measurement
EFO:0005000	leptin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Corticosterone	increases expression	1
Dexamethasone	increases expression, increases reaction	1
Endosulfan	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Glucose-6-Phosphate	increases hydrolysis	1

Clinical trials (associated diseases)

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