GFPT1

Chr 2

glutamine--fructose-6-phosphate transaminase 1

Also known as: CMS12, CMSTA1, GFA, GFAT, GFAT 1, GFAT1, GFAT1m, GFPT

NCBI Gene: 2673ENSG00000198380UniProt: Q06210

This gene encodes the first and rate-limiting enzyme of the hexosamine pathway and controls the flux of glucose into the hexosamine pathway. The product of this gene catalyzes the formation of glucosamine 6-phosphate. [provided by RefSeq, Sep 2008]

Primary Disease Associations & Inheritance

UniProtMyasthenic syndrome, congenital, 12
377
ClinVar variants
32
Pathogenic / LP
0.90
pLI score
0
Active trials
Clinical Summary— GFPT1
🧬
Gene-Disease Validity (ClinGen)
congenital myasthenic syndrome 12 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 126 VUS of 377 total submissions
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.900
Z-score 4.92
OE 0.19 (0.11–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.35Z-score
OE missense 0.38 (0.34–0.44)
151 obs / 393.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.11–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.38 (0.34–0.44)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 8 / 42.7Missense obs/exp: 151 / 393.8Syn Z: 1.04

ClinVar Variant Classifications

377 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic13
VUS126
Likely Benign193
Benign21
Conflicting5
19
Pathogenic
13
Likely Pathogenic
126
VUS
193
Likely Benign
21
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
10
0
19
Likely Pathogenic
7
3
3
0
13
VUS
1
109
16
0
126
Likely Benign
0
0
120
73
193
Benign
0
0
20
1
21
Conflicting
—5
Total1511416974377

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GFPT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — GFPT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
Congenital myasthenic syndromes.
Finsterer J·Orphanet J Rare Dis
2019
Endogenous glutamate determines ferroptosis sensitivity via ADCY10-dependent YAP suppression in lung adenocarcinoma.
Zhang X et al.·Theranostics
2021
Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort.
Polavarapu K et al.·Brain
2024Cohort
Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.
Theuriet J et al.·Brain
2024
Congenital Myasthenic Syndromes in Belgium: Genetic and Clinical Characterization of Pediatric and Adult Patients.
Smeets N et al.·Pediatr Neurol
2024Cohort
Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.
Patterson AR et al.·Sci Immunol
2024Functional
GFPT1-myasthenia: clinical, structural, and electrophysiologic heterogeneity.
Selcen D et al.·Neurology
2013
GFPT1 facilitates immune escape in breast cancer by promoting the OGT-mediate O-GlcNAcylation of CD39.
Zhen H et al.·Autoimmunity
2025
O-GlcNAcylation Stabilizes NEK7 to Drive Podocyte Pyroptosis in Diabetic Kidney Disease.
Chen W et al.·Diabetes
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Dysfunctional decidual CD2+CD4+T cells regulated by Rev-erbα - GFPT1 - GPI anchored CD58 axis of decidual stromal cells underlies sleep disturbance induced recurrent pregnancy loss.
Qiu M et al.·Front Immunol
2026🔓 Open AccessFunctional
Expanding the phenotypic and imaging spectrum of GFPT1-related congenital myasthenic syndromes: a Brazilian case series.
Camelo-Filho AE et al.·Front Neurol
2025🔓 Open AccessCohort
Galactose treatment rescues neuromuscular junction transmission in glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) deficient mice.
Holland SH et al.·Hum Mol Genet
2025
Combinational Analysis of Metabolomic and O-GlcNAcylation Omics Reveals the HBP Metabolic Regulation of Chemoresistance via GFPT1/NR3C1 O-GlcNAcylation/GPX4 Axis.
Zhou X et al.·Research (Wash D C)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools