GFPT1

glutamine--fructose-6-phosphate transaminase 1

Basic information

Region (hg38): 2:69319780-69387250

Previous symbols: [ "GFPT" ]

Links

ENSG00000198380 ∙ NCBI:2673 ∙ OMIM:138292 ∙ HGNC:4241 ∙ Uniprot:Q06210 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 12 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 12 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 12 (Moderate), mode of inheritance: AR
• congenital myasthenic syndromes with glycosylation defect (Supportive), mode of inheritance: AR
• congenital myasthenic syndrome 12 (Definitive), mode of inheritance: AR
• congenital myasthenic syndrome 12 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital 12	AR	Musculoskeletal; Pharmacogenomic	Acetylcholinesterase inhibitors have been shown to result in a favorable treatment response; Avoidance of certain agents involved in neuromuscular transmission is indicated (eg, ciprofloxacin, chloroquine, lithium, phenytoin, beta-blockers, procainamide); Additional neurologic monitoring in pregnancy may be beneficial	Musculoskeletal; Neurologic	8664562; 12467753; 21310273; 23108489

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFPT1 gene.

• Congenital myasthenic syndrome 12 (17 variants)
• not provided (3 variants)
• Congenital myasthenic syndrome (1 variants)
• GFPT1-related disorder (1 variants)
• Abnormality of the musculature (1 variants)
• GFPT1-related myasthenic syndrome (1 variants)
• Congenital myasthenic syndrome 12;Congenital myasthenic syndrome 4C (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFPT1 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	66	3	71
missense	1	4	120			125
nonsense	7	1				8
start loss						0
frameshift	8	2				10
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region		1	9	18	2	30
non coding			113	96	60	269
Total	17	10	238	162	63

Highest pathogenic variant AF is 0.0000197

Variants in GFPT1

This is a list of pathogenic ClinVar variants found in the GFPT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-69319811-C-T		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69319823-A-G		Congenital myasthenic syndrome 12	Benign (Jan 13, 2018)
2-69319905-C-T		Congenital myasthenic syndrome 12	Uncertain significance (Jan 12, 2018)
2-69320053-G-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320063-T-C		Congenital myasthenic syndrome 12	Uncertain significance (Jan 12, 2018)
2-69320087-A-C		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320095-G-A		Congenital myasthenic syndrome 12	Benign (Jan 12, 2018)
2-69320104-G-C		Congenital myasthenic syndrome 12	Benign (Jan 13, 2018)
2-69320150-C-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 12, 2018)
2-69320173-G-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320186-C-A		Congenital myasthenic syndrome 12	Likely benign (Jan 13, 2018)
2-69320287-AC-A		Congenital Myasthenic Syndrome, Recessive	Uncertain significance (Jun 14, 2016)
2-69320305-T-C		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320369-G-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 12, 2018)
2-69320389-C-T		Congenital myasthenic syndrome 12	Uncertain significance (Jan 12, 2018)
2-69320425-T-C		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320476-A-G		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320516-G-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 12, 2018)
2-69320675-C-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320713-G-A		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320725-T-C		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320741-T-C		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320752-C-T		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320757-C-T		Congenital myasthenic syndrome 12	Uncertain significance (Jan 13, 2018)
2-69320787-C-CA		Congenital Myasthenic Syndrome, Recessive	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFPT1	protein_coding	protein_coding	ENST00000357308	20	67478

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.900	0.100	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.35	151	394	0.383	0.0000220	4617
Missense in Polyphen		30	155.75	0.19262		1850
Synonymous	1.04	112	127	0.883	0.00000641	1300
Loss of Function	4.92	8	42.7	0.187	0.00000250	488

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000183	0.000183
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000627	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes ARNTL/BMAL1 and CRY1.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;2-Hydroxyglutric Aciduria (D And L Form);Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Salla Disease/Infantile Sialic Acid Storage Disease;Glutamate Metabolism;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;XBP1(S) activates chaperone genes;Aminosugars metabolism;Fructose Mannose metabolism;Post-translational protein modification;Metabolism of proteins;UDP-<i>N</i>-acetyl-D-glucosamine biosynthesis II;Synthesis of UDP-N-acetyl-glucosamine;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.509

Intolerance Scores

• loftool: 0.332
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.701
• hipred: Y
• hipred_score: 0.663
• ghis: 0.638

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gfpt1
• Phenotype: skeleton phenotype; immune system phenotype; limbs/digits/tail 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)

Zebrafish Information Network

• Gene name: gfpt1
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: fructose 6-phosphate metabolic process;UDP-N-acetylglucosamine metabolic process;UDP-N-acetylglucosamine biosynthetic process;energy reserve metabolic process;protein N-linked glycosylation;glutamine metabolic process;circadian regulation of gene expression;IRE1-mediated unfolded protein response
• Cellular component: cytosol;extracellular exosome
• Molecular function: glutamine-fructose-6-phosphate transaminase (isomerizing) activity;carbohydrate derivative binding