Neonatal glycine encephalopathy
disease diseaseOn this page
Also known as classic glycine encephalopathyneonatal NKHneonatal non-ketotic hyperglycinemia
Summary
Neonatal glycine encephalopathy (MONDO:0017353) is a disease with 3 cohort genes. The dominant Reactome pathway is Glycine degradation (3 cohort genes).
At a glance
- Prevalence: Unknown (Worldwide)
- Cohort genes: 3
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | neonatal glycine encephalopathy |
| Mondo ID | MONDO:0017353 |
| Orphanet | 289857 |
| ICD-11 | 414151121 |
| UMLS | C5548200 |
| MedGen | 1785446 |
| GARD | 0017332 |
| Is cancer (heuristic) | no |
Also known as: classic glycine encephalopathy · neonatal NKH · neonatal non-ketotic hyperglycinemia
Data availability: 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › glycine encephalopathy › neonatal glycine encephalopathy
Related subtypes (5): atypical glycine encephalopathy, infantile glycine encephalopathy, multiple mitochondrial dysfunctions syndrome 7, glycine encephalopathy 1, glycine encephalopathy 2
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 24 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| AMT | Definitive | Autosomal recessive | glycine encephalopathy | 8 |
| GLDC | Definitive | Autosomal recessive | glycine encephalopathy | 8 |
| GCSH | Supportive | Autosomal recessive | neonatal glycine encephalopathy | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GCSH | Orphanet:289857 | Neonatal glycine encephalopathy |
| GCSH | Orphanet:289860 | Infantile glycine encephalopathy |
| GCSH | Orphanet:289863 | Atypical glycine encephalopathy |
| GLDC | Orphanet:289857 | Neonatal glycine encephalopathy |
| GLDC | Orphanet:289860 | Infantile glycine encephalopathy |
| GLDC | Orphanet:289863 | Atypical glycine encephalopathy |
| AMT | Orphanet:289857 | Neonatal glycine encephalopathy |
| AMT | Orphanet:289860 | Infantile glycine encephalopathy |
| AMT | Orphanet:289863 | Atypical glycine encephalopathy |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| GCSH | HGNC:4208 | ENSG00000140905 | P23434 | Glycine cleavage system H protein, mitochondrial | gencc |
| GLDC | HGNC:4313 | ENSG00000178445 | P23378 | Glycine dehydrogenase (decarboxylating), mitochondrial | gencc |
| AMT | HGNC:473 | ENSG00000145020 | P48728 | Aminomethyltransferase, mitochondrial | gencc |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GCSH | Glycine cleavage system H protein, mitochondrial | The glycine cleavage system catalyzes the degradation of glycine. |
| GLDC | Glycine dehydrogenase (decarboxylating), mitochondrial | The glycine cleavage system catalyzes the degradation of glycine. |
| AMT | Aminomethyltransferase, mitochondrial | The glycine cleavage system catalyzes the degradation of glycine. |
Protein-family classification
Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Enzyme (other) | 3 | 12.0× | 6e-04 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GCSH | Enzyme (other) | yes | 1.4.1.27 | Biotin_lipoyl, GCV_H, 2-oxoA_DH_lipoyl-BS |
| GLDC | Enzyme (other) | yes | 1.4.1.27 | ArAA_b-elim_lyase/Thr_aldolase, GcvP, PyrdxlP-dep_Trfase_major |
| AMT | Enzyme (other) | yes | 1.4.1.27 | GCVT_N, GcvT, GcvT_C |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| liver | 2 |
| right lobe of liver | 2 |
| C1 segment of cervical spinal cord | 1 |
| amygdala | 1 |
| substantia nigra | 1 |
| nephron tubule | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GCSH | 134 | ubiquitous | marker | C1 segment of cervical spinal cord, substantia nigra, amygdala |
| GLDC | 216 | broad | marker | right lobe of liver, liver, nephron tubule |
| AMT | 140 | broad | yes | right lobe of liver, liver, right uterine tube |
Protein interactions among cohort
Intra-cohort edges: 3.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| GLDC | 2,559 |
| GCSH | 2,079 |
| AMT | 1,716 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| AMT | GCSH | string_interaction |
| AMT | GLDC | string_interaction |
| GCSH | GLDC | intact, string_interaction |
Structural data
PDB: 3 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| GCSH | P23434 | 3 |
| GLDC | P23378 | 3 |
| AMT | P48728 | 2 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Glycine degradation | 3 | 1631.4× | 3e-10 | GCSH, GLDC, AMT |
| Protein lipoylation | 1 | 346.1× | 0.003 | GCSH |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| glycine decarboxylation via glycine cleavage system | 3 | 5617.3× | 6e-12 | GCSH, GLDC, AMT |
| glycine catabolic process | 2 | 5617.3× | 5e-08 | GLDC, AMT |
| response to methylamine | 1 | 5617.3× | 3e-04 | GLDC |
| response to lipoic acid | 1 | 2808.7× | 4e-04 | GLDC |
| cellular response to leukemia inhibitory factor | 1 | 53.0× | 0.019 | GLDC |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3
Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| GCSH | 0 | 0 |
| GLDC | 0 | 0 |
| AMT | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| GCSH | 1.4.1.27, 1.4.4.2 | glycine cleavage system, glycine dehydrogenase (aminomethyl-transferring) |
| GLDC | 1.4.1.27, 1.4.4.2 | glycine cleavage system, glycine dehydrogenase (aminomethyl-transferring) |
| AMT | 1.4.1.27, 2.1.2.10 | glycine cleavage system, aminomethyltransferase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 3 | GCSH, GLDC, AMT |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| GCSH | 0 | — |
| GLDC | 0 | — |
| AMT | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.