G6PC3

glucose-6-phosphatase catalytic subunit 3, the group of Glucose 6-phosphatases, catalytic

Basic information

Region (hg38): 17:44070619-44082151

Links

ENSG00000141349 ∙ NCBI:92579 ∙ OMIM:611045 ∙ HGNC:24861 ∙ Uniprot:Q9BUM1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (Supportive), mode of inheritance: AR
• autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (Definitive), mode of inheritance: AR
• autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital, 4, autosomal recessive	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Genitourinary; Hematologic	Antiinfectious prophylaxis (including with G-CSF) and early and aggressive treatment of infections may be beneficial; Awareness of other manifestations, including affecting the cardiac, endocrine, and urogenital systems may allow early diagnosis and treatment	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Renal	19696212; 19118303; 20799326; 20616219; 20717171; 21285905; 22050868

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the G6PC3 gene.

• Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (259 variants)
• not provided (37 variants)
• Inborn genetic diseases (19 variants)
• not specified (12 variants)
• Severe congenital neutropenia (2 variants)
• G6PC3-related condition (1 variants)
• Inherited Immunodeficiency Diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the G6PC3 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			2	61	2	65
missense	3	2	111	1	2	119
nonsense	6	1				7
start loss						0
frameshift	10					10
inframe indel	1		3			4
splice donor/acceptor (+/-2bp)	4	2				6
splice region			6	8	1	15
non coding			27	18	9	54
Total	24	5	143	80	13

Highest pathogenic variant AF is 0.0000592

Variants in G6PC3

This is a list of pathogenic ClinVar variants found in the G6PC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-44070735-A-G		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Jan 13, 2018)
17-44070772-C-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Jan 13, 2018)
17-44070775-T-G		Severe congenital neutropenia	Uncertain significance (Jun 14, 2016)
17-44070788-C-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Jan 13, 2018)
17-44070802-G-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Jan 12, 2018)
17-44070804-G-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Jan 12, 2018)
17-44070811-T-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Jan 13, 2018)
17-44070814-T-C		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Benign (Jan 12, 2018)
17-44070817-G-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Nov 16, 2017)
17-44070837-C-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Benign (Jul 27, 2018)
17-44070918-G-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Jan 13, 2018)
17-44070962-C-T		G6PC3-related disorder	Likely benign (Sep 17, 2020)
17-44070968-G-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Pathogenic (Feb 16, 2023)
17-44070974-C-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Jan 08, 2024)
17-44070975-A-G		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Sep 19, 2022)
17-44070976-C-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Aug 31, 2021)
17-44070977-G-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Aug 19, 2023)
17-44070977-G-C		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Nov 28, 2023)
17-44070981-G-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Oct 24, 2022)
17-44070986-G-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Dec 14, 2023)
17-44070989-C-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Jul 13, 2023)
17-44070992-C-T		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Jan 02, 2024)
17-44070995-G-A		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Feb 11, 2023)
17-44070995-G-C		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Likely benign (Aug 05, 2022)
17-44070996-A-G		Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	Uncertain significance (Oct 30, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
G6PC3	protein_coding	protein_coding	ENST00000269097	6	5607

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000472	0.862	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.696	161	188	0.857	0.0000112	2209
Missense in Polyphen		51	67.195	0.75898		802
Synonymous	-1.37	91	75.8	1.20	0.00000413	738
Loss of Function	1.47	11	17.7	0.623	9.60e-7	164

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00117	0.00117
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000163	0.000163
South Asian	0.000173	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function. {ECO:0000269|PubMed:12370122, ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915}.
• Disease: DISEASE: Dursun syndrome (DURSS) [MIM:612541]: A disease characterized by pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, intermittent neutropenia, lymphopenia, monocytosis and anemia. {ECO:0000269|PubMed:20799326}. 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);PI3K-Akt Signaling Pathway;Metabolism of carbohydrates;glycogenolysis;Metabolism;gluconeogenesis;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• loftool: 0.726
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

• pHI: 0.194
• hipred: N
• hipred_score: 0.282
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.138

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: G6pc3
• 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); hematopoietic system phenotype; immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: gluconeogenesis;glucose-6-phosphate transport;dephosphorylation;glucose 6-phosphate metabolic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: glucose-6-phosphatase activity