SLC37A4

solute carrier family 37 member 4, the group of Solute carrier family 37

Basic information

Region (hg38): 11:119023750-119030906

Previous symbols: [ "G6PT1", "G6PT2", "G6PT3" ]

Links

ENSG00000137700 ∙ NCBI:2542 ∙ OMIM:602671 ∙ HGNC:4061 ∙ Uniprot:O43826 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease type 1 due to SLC37A4 mutation (Definitive), mode of inheritance: AR
• glycogen storage disease Ib (Strong), mode of inheritance: AR
• glycogen storage disease Ib (Strong), mode of inheritance: AR
• glycogen storage disease Ib (Strong), mode of inheritance: AR
• glycogen storage disease Ib (Strong), mode of inheritance: AR
• glycogen storage disease Ib (Definitive), mode of inheritance: AR
• congenital disorder of glycosylation, type IIw (Strong), mode of inheritance: AD
• glycogen storage disease Ib (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease Ib; Glycogen storage disease Ic; Glycogen storage disease Id; Congenital disorder of glycosylation, type IIw	AR	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Gastrointestinal; Oncologic; Renal	In Glycogen storage disease, dietary measures can be beneficial 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; G-CSF may be beneficial due to recurrent infections; Individuals with Congenital disorder of glycosylation, type IIw have been described to have hepatic dysfunction, including involving coagulopathy, as well as congenital cardiac anomalies requiring surgical interventions, and awareness may allow early diagnosis and management	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Oncologic; Renal	4300573; 212064; 6928812; 6578929; 6298622; 6309784; 3860000; 3459848; 3464427; 2311631; 1719175; 1375344; 8319729; 273986; 8758135; 9428641; 9758626; 9686363; 10931421; 12576310; 20301489; 21575371; 21599942; 21629566; 31536830; 32884905; 33728255; 33964207

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC37A4 gene.

• Glucose-6-phosphate transport defect (791 variants)
• not provided (113 variants)
• Glycogen storage disease, type I (48 variants)
• Inborn genetic diseases (42 variants)
• not specified (28 variants)
• Phosphate transport defect;Congenital disorder of glycosylation, type IIw;Glucose-6-phosphate transport defect (20 variants)
• Phosphate transport defect (17 variants)
• Congenital disorder of glycosylation, type IIw;Phosphate transport defect;Glucose-6-phosphate transport defect (13 variants)
• Glucose-6-phosphate transport defect;Congenital disorder of glycosylation, type IIw;Phosphate transport defect (12 variants)
• Glucose-6-phosphate transport defect;Phosphate transport defect;Congenital disorder of glycosylation, type IIw (11 variants)
• SLC37A4-related condition (8 variants)
• Phosphate transport defect;Glucose-6-phosphate transport defect;Congenital disorder of glycosylation, type IIw (5 variants)
• Phosphate transport defect;Glucose-6-phosphate transport defect (3 variants)
• Congenital disorder of glycosylation, type IIw (2 variants)
• Glycogen storage disease type 1 due to SLC37A4 mutation (1 variants)
• Glycogen storage disease (1 variants)
• See cases (1 variants)
• 6 conditions (1 variants)
• Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (1 variants)
• Congenital disorder of glycosylation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC37A4 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			10	185	4	199
missense	7	19	270	17	4	317
nonsense	14	9				23
start loss						0
frameshift	27	32	1	1	1	62
inframe indel		1	9	1		11
splice donor/acceptor (+/-2bp)	9	18	36	35	1	99
splice region						0
non coding			52	86	25	163
Total	57	79	378	325	35

Highest pathogenic variant AF is 0.000256

Variants in SLC37A4

This is a list of pathogenic ClinVar variants found in the SLC37A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-119024492-A-G		Glycogen storage disease, type I	Benign (Jan 13, 2018)
11-119024550-G-C		Glycogen storage disease, type I	Uncertain significance (Jan 12, 2018)
11-119024572-A-G		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024612-G-A		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024627-A-G		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024647-A-G		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024706-G-A		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024771-C-A		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024772-G-A		Glycogen storage disease, type I	Uncertain significance (Jan 13, 2018)
11-119024785-C-G		Glycogen storage disease, type I	Benign (Jun 23, 2018)
11-119024841-CCTT-C		not specified	Uncertain significance (Jul 15, 2022)
11-119024879-G-A		Glycogen storage disease, type I	Uncertain significance (Jan 12, 2018)
11-119024893-C-T			Benign (May 14, 2015)
11-119024898-C-T		Glucose-6-phosphate transport defect	Uncertain significance (Mar 23, 2018)
11-119024899-C-T		not specified • Glucose-6-phosphate transport defect	Conflicting classifications of pathogenicity (Jan 15, 2018)
11-119024903-A-C		Glucose-6-phosphate transport defect	Uncertain significance (Mar 16, 2017)
11-119024903-ACT-A		Glucose-6-phosphate transport defect	Uncertain significance (Jul 28, 2017)
11-119024905-T-A		Glucose-6-phosphate transport defect	Uncertain significance (Mar 07, 2018)
11-119024905-T-C		Glucose-6-phosphate transport defect	Uncertain significance (Nov 03, 2017)
11-119024905-T-G		Glycogen storage disease, type I • SLC37A4-related disorder	Conflicting classifications of pathogenicity (Feb 21, 2024)
11-119024909-T-C		Glucose-6-phosphate transport defect	Uncertain significance (Aug 11, 2017)
11-119024909-TTCAC-T		Glucose-6-phosphate transport defect	Conflicting classifications of pathogenicity (Feb 14, 2023)
11-119024911-C-T		Glucose-6-phosphate transport defect	Likely benign (Aug 31, 2022)
11-119024913-C-G		Glucose-6-phosphate transport defect • Phosphate transport defect;Glucose-6-phosphate transport defect;Congenital disorder of glycosylation, type IIw	Uncertain significance (Oct 04, 2021)
11-119024913-C-T		Glucose-6-phosphate transport defect	Likely benign (Mar 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC37A4	protein_coding	protein_coding	ENST00000357590	10	6793

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000167	0.970	377	124265	0	124642	0.945

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00226	249	249	1.00	0.0000132	2868
Missense in Polyphen		65	75.078	0.86577		848
Synonymous	-0.455	104	98.3	1.06	0.00000508	929
Loss of Function	1.98	11	20.7	0.531	9.83e-7	224

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.00	1.94
Ashkenazi Jewish	1.00	0.949
East Asian	1.00	0.968
Finnish	1.00	0.964
European (Non-Finnish)	1.00	0.937
Middle Eastern	1.00	0.968
South Asian	1.00	0.955
Other	1.00	0.945

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inorganic phosphate and glucose-6-phosphate antiporter of the endoplasmic reticulum. Transports cytoplasmic glucose-6- phosphate into the lumen of the endoplasmic reticulum and translocates inorganic phosphate into the opposite direction. Forms with glucose-6-phosphatase the complex responsible for glucose production through glycogenolysis and gluconeogenesis. Hence, it plays a central role in homeostatic regulation of blood glucose levels. {ECO:0000269|PubMed:10026167, ECO:0000269|PubMed:21949678}.
• Disease: DISEASE: Glycogen storage disease 1C (GSD1C) [MIM:232240]: 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:10482962, ECO:0000269|PubMed:9758626}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glycogen storage disease 1D (GSD1D) [MIM:232240]: 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:9758626}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Carbohydrate digestion and absorption - Homo sapiens (human);Mitochondrial Electron Transport Chain;Gluconeogenesis;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Metabolism of carbohydrates;Metabolism;Phosphatidylinositol phosphate metabolism;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.325

Haploinsufficiency Scores

• pHI: 0.215
• hipred: N
• hipred_score: 0.306

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.367

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc37a4
• Phenotype: hematopoietic system 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); 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; immune 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); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: glucose metabolic process;gluconeogenesis;carbohydrate transport;glucose-6-phosphate transport;phosphate ion transmembrane transport
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane
• Molecular function: transporter activity;glucose-6-phosphate transmembrane transporter activity;glucose 6-phosphate:inorganic phosphate antiporter activity