GLDC

Chr 9AR

glycine decarboxylase

NCBI Gene: 2731ENSG00000178445UniProt: P23378

The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH)

Primary Disease Associations & Inheritance

Glycine encephalopathy1MIM #605899
AR
UniProtNon-ketotic hyperglycinemia
2912
ClinVar variants
112
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GLDC
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 Pathogenic / Likely Pathogenic· 151 VUS of 2912 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.11LOEUF
pLI 0.000
Z-score 0.91
OE 0.86 (0.68–1.11)
Tolerant

Highly tolerant — LoF variants common in population

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.
-1.59Z-score
OE missense 1.19 (1.12–1.27)
645 obs / 541.0 exp
Tolerant

Tolerant to missense variation

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.0.86 (0.68–1.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.19 (1.12–1.27)
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.1.43
0≤1.21.6
LoF obs/exp: 46 / 53.2Missense obs/exp: 645 / 541.0Syn Z: -4.81

ClinVar Variant Classifications

2912 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic44
VUS151
Likely Benign219
Benign1
Conflicting1
68
Pathogenic
44
Likely Pathogenic
151
VUS
219
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
4
46
0
68
Likely Pathogenic
19
11
14
0
44
VUS
1
126
11
13
151
Likely Benign
0
1
132
86
219
Benign
0
0
1
0
1
Conflicting
—1
Total3814220499484

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

View in ClinVar →

Protein Context — Lollipop Plot

GLDC · protein map & ClinVar variants

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

Gene2Phenotype Curations

GLDC-related glycine encephalopathy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glycine encephalopathy1

MIM #605899

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT.
Coughlin CR 2nd et al.·Genet Med
2017
GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC.
Xie H et al.·Front Immunol
2022
Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.
Chen MK et al.·Int J Biol Sci
2023
Glycine decarboxylase advances IgA nephropathy by boosting mesangial cell proliferation through the pyrimidine pathway.
Xiong Y et al.·EMBO Mol Med
2025
Downregulation of glycine decarboxylase enhanced cofilin-mediated migration in hepatocellular carcinoma cells.
Zhuang H et al.·Free Radic Biol Med
2018
Integrative Approach to Predict Severity in Nonketotic Hyperglycinemia.
Kuseyri Hübschmann O et al.·Ann Neurol
2022
Identification of a new GLDC gene alternative splicing variant and its protumorigenic roles in lung cancer.
Yuan Y et al.·Future Oncol
2019
Atypical variants of nonketotic hyperglycinemia.
Dinopoulos A et al.·Mol Genet Metab
2005Review
Homozygosity for disease-causing variants in AMT and GLDC in a patient with severe nonketotic hyperglycinemia.
Drackley A et al.·Am J Med Genet A
2024Case report
Glycine by MR spectroscopy is an imaging biomarker of glioma aggressiveness.
Tiwari V et al.·Neuro Oncol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Phosphorylation of FBXL3 mediates GLDC polyubiquitination to suppress MHC-I expression and promote cancer immune evasion.
Liu R et al.·Cell Insight
2026🔓 Open Access
Glycine Reverses Behavioral Deficits in a Mouse Model for Psychosis With 4 Copies of the Gldc Gene.
Wang M et al.·Pharmacol Res Perspect
2025🔓 Open AccessFunctional
Corrigendum to "GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma" [Adv. Pharmaceut. Sci. (3), (2025), 100072].
Song Z et al.·Pharm Sci Adv
2025🔓 Open Access
Possible Founder Effect of Glycine Encephalopathy: Evidence of a GLDC c.2714T>G (p.Val905Gly) Common Variant in the Paisa Community Based in Cali, Colombia.
Sinisterra-Diaz SE et al.·Am J Med Genet A
2025
GLDC attenuates liver ischemia-reperfusion injury by inhibiting macrophage recruitment and activation via PTBP1/P2RY6.
Li Z et al.·Cell Signal
2025
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