AMT

Summary

AMT (aminomethyltransferase, HGNC:473) is a protein-coding gene on chromosome 3p21.31, encoding Aminomethyltransferase, mitochondrial (P48728). The glycine cleavage system catalyzes the degradation of glycine.

This gene encodes one of four critical components of the glycine cleavage system. Mutations in this gene have been associated with glycine encephalopathy. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 275 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycine encephalopathy (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 774 total — 61 pathogenic, 61 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_000481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:473
Approved symbol	AMT
Name	aminomethyltransferase
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	GCST, NKH
Ensembl gene	ENSG00000145020
Ensembl biotype	protein_coding
OMIM	238310
Entrez	275

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 35 retained_intron, 15 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000273588, ENST00000395338, ENST00000399379, ENST00000427987, ENST00000430521, ENST00000458307, ENST00000461210, ENST00000462048, ENST00000465925, ENST00000473163, ENST00000476127, ENST00000476226, ENST00000476828, ENST00000478594, ENST00000480957, ENST00000487589, ENST00000491800, ENST00000493046, ENST00000495436, ENST00000498571, ENST00000538581, ENST00000635772, ENST00000635798, ENST00000635808, ENST00000635889, ENST00000635907, ENST00000635936, ENST00000636023, ENST00000636070, ENST00000636148, ENST00000636188, ENST00000636199, ENST00000636522, ENST00000636587, ENST00000636594, ENST00000636597, ENST00000636725, ENST00000636803, ENST00000636865, ENST00000636871, ENST00000636978, ENST00000636991, ENST00000637059, ENST00000637114, ENST00000637268, ENST00000637291, ENST00000637455, ENST00000637457, ENST00000637527, ENST00000637682, ENST00000637684, ENST00000637821, ENST00000637914, ENST00000637982, ENST00000637994, ENST00000638063, ENST00000638092

RefSeq mRNA: 4 — MANE Select: NM_000481 NM_000481, NM_001164710, NM_001164711, NM_001164712

CCDS: CCDS2797, CCDS54583, CCDS54584, CCDS54585

Canonical transcript exons

ENST00000273588 — 9 exons

Exon	Start	End
ENSE00003482904	49420211	49420342
ENSE00003564602	49417818	49417973
ENSE00003567679	49419710	49419788
ENSE00003593967	49421492	49421572
ENSE00003611044	49418971	49419151
ENSE00003620797	49419260	49419405
ENSE00003656537	49422104	49422271
ENSE00003794373	49422361	49422473
ENSE00003798868	49416778	49417718

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 94.65.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2658 / max 108.5483, expressed in 512 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42263	3.1053	509
42262	0.1605	93

Top tissues by expression

140 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	94.65	gold quality
liver	UBERON:0002107	93.23	gold quality
right uterine tube	UBERON:0001302	91.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.49	gold quality
cerebellar hemisphere	UBERON:0002245	91.01	gold quality
cerebellar cortex	UBERON:0002129	91.00	gold quality
cerebellum	UBERON:0002037	90.96	gold quality
apex of heart	UBERON:0002098	90.08	gold quality
mucosa of transverse colon	UBERON:0004991	89.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.17	gold quality
pituitary gland	UBERON:0000007	89.07	gold quality
adult mammalian kidney	UBERON:0000082	88.70	gold quality
body of pancreas	UBERON:0001150	88.68	gold quality
left ovary	UBERON:0002119	88.23	gold quality
adenohypophysis	UBERON:0002196	88.09	gold quality
heart left ventricle	UBERON:0002084	88.05	gold quality
fundus of stomach	UBERON:0001160	87.91	gold quality
right atrium auricular region	UBERON:0006631	87.86	gold quality
duodenum	UBERON:0002114	87.69	gold quality
cortex of kidney	UBERON:0001225	87.62	gold quality
transverse colon	UBERON:0001157	87.54	gold quality
ovary	UBERON:0000992	87.45	gold quality
kidney	UBERON:0002113	87.35	gold quality
rectum	UBERON:0001052	87.34	gold quality
heart	UBERON:0000948	87.10	gold quality
right ovary	UBERON:0002118	87.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.06	gold quality
left adrenal gland cortex	UBERON:0035825	86.91	gold quality
right adrenal gland	UBERON:0001233	86.83	gold quality
prostate gland	UBERON:0002367	86.77	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting AMT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-378A-5P	99.65	66.33	1311

Literature-anchored findings (GeneRIF, showing 5)

• The Relish/miR-275/Dredd mediated negative feedback loop is crucial to restoring immune homeostasis of Drosophila Imd pathway. (PMID:37804878)
• x-ray crystallographic structure of human T-protein of glycine cleavage system (PMID:16051266)
• Two unique non-synonymous changes were identified in the AMT gene in patients with neural tube defects. (PMID:22171071)
• Data indicate no mutation was found in glycine cleavage system protein-H (GCSH) and suggest that mutations in both glycine decarboxylase (GLDC) and aminomethyltransferase (AMT) are the main cause of glycine encephalopathy in Malaysian population. (PMID:25231368)
• The position and frequency of the breakpoint for CNVs correlated with intron size and presence of Alu elements. Missense mutations, most often recurring, were the most common type of disease-causing mutation in AMT (PMID:27362913)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	amt	ENSDARG00000010862
mus_musculus	Amt	ENSMUSG00000032607
rattus_norvegicus	Amt	ENSRNOG00000050214
drosophila_melanogaster	CG6415	FBGN0032287
caenorhabditis_elegans		WBGENE00017765

Paralogs (10): L2HGDH (ENSG00000087299), YPEL3 (ENSG00000090238), PDPR (ENSG00000090857), YPEL1 (ENSG00000100027), FOXRED1 (ENSG00000110074), YPEL5 (ENSG00000119801), SARDH (ENSG00000123453), DMGDH (ENSG00000132837), YPEL4 (ENSG00000166793), YPEL2 (ENSG00000175155)

Protein

Protein identifiers

Aminomethyltransferase, mitochondrial — P48728 (reviewed: P48728)

Alternative names: Glycine cleavage system T protein

All UniProt accessions (16): P48728, A0A1B0GTA8, A0A1B0GTB6, A0A1B0GTM2, A0A1B0GTV8, A0A1B0GU55, A0A1B0GUK9, A0A1B0GUU7, A0A1B0GV07, A0A1B0GVD0, A0A1B0GVP5, A0A1B0GWC4, B3KTU4, C9JXJ4, F8WF62, H0Y695

UniProt curated annotations — full annotation on UniProt →

Function. The glycine cleavage system catalyzes the degradation of glycine.

Subunit / interactions. The glycine cleavage system is composed of four proteins: P, T, L and H.

Subcellular location. Mitochondrion.

Disease relevance. Glycine encephalopathy 2 (GCE2) [MIM:620398] A form of glycine encephalopathy, a metabolic disorder characterized by a high concentration of glycine in the body fluids. Affected individuals typically have severe neurological symptoms, including seizure, lethargy, and muscular hypotonia soon after birth. Most of them die within the neonatal period. Atypical cases have later disease onset and less severely affected psychomotor development. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the GcvT family.

Isoforms (4)

UniProt ID	Names	Canonical?
P48728-1	1	yes
P48728-2	2
P48728-3	3
P48728-4	4

RefSeq proteins (4): NP_000472, NP_001158182, NP_001158183, NP_001158184 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006222	GCVT_N	Domain
IPR006223	GcvT	Family
IPR013977	GcvT_C	Domain
IPR027266	TrmE/GcvT-like	Homologous_superfamily
IPR028896	GcvT/YgfZ/DmdA	Family
IPR029043	GcvT/YgfZ_C	Homologous_superfamily

Pfam: PF01571, PF08669

Enzyme classification (BRENDA):

• EC 1.4.1.27 — glycine cleavage system (BRENDA: 15 organisms, 4 substrates, 5 inhibitors, 6 Km, 0 kcat entries)
• EC 2.1.2.10 — aminomethyltransferase (BRENDA: 12 organisms, 30 substrates, 2 inhibitors, 21 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5,10-METHYLENETETRAHYDROFOLATE	0.0677–0.151	5
5,10-METHYLENETETRAHYDROPTEROYLTETRAGLUTAMATE	0.0092–0.0382	5
NH4CL	65.4–256	4
REDUCED H-PROTEIN	0.0007–0.0169	4
GLYCINE	6.6–40	2
TETRAHYDROFOLATE	0.05–0.17	2
LIPOIC ACID	0.83	1
S-AMINOMETHYLDIHYDROLIPOYLPROTEIN	0.0037	1
TETRAHYDROFOLATE	0.17	1

Catalyzed reactions (Rhea), 1 shown:

• N(6)-[(R)-S(8)-aminomethyldihydrolipoyl]-L-lysyl-[protein] + (6S)-5,6,7,8-tetrahydrofolate = N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NH4(+) (RHEA:16945)

UniProt features (57 total): strand 20, helix 13, sequence variant 11, binding site 3, turn 3, splice variant 3, transit peptide 1, chain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1WSR	X-RAY DIFFRACTION	2
1WSV	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48728-F1	93.66	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 232; 261; 399

Mutagenesis-validated functional residues (1):

Position	Phenotype
129	loss of aminomethyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6783984	Glycine degradation

MSigDB gene sets: 148 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, KEGG_ONE_CARBON_POOL_BY_FOLATE, MODULE_66, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, MODULE_294, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_GLYCINE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, MODULE_88, GOBP_AMINO_ACID_CATABOLIC_PROCESS, URS_ADIPOCYTE_DIFFERENTIATION_UP, MODULE_11, MODULE_60

GO Biological Process (3): glycine catabolic process (GO:0006546), glycine decarboxylation via glycine cleavage system (GO:0019464), methylation (GO:0032259)

GO Molecular Function (5): aminomethyltransferase activity (GO:0004047), transaminase activity (GO:0008483), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (4): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), glycine cleavage complex (GO:0005960)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glyoxylate metabolism and glycine degradation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycine metabolic process	1
amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
glycine catabolic process	1
metabolic process	1
hydroxymethyl-, formyl- and related transferase activity	1
transferase activity, transferring nitrogenous groups	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
oxidoreductase complex	1
transferase complex	1

Protein interactions and networks

STRING

1704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMT	GLDC	P23378	996
AMT	GCSH	P23434	991
AMT	OCA2	Q04671	986
AMT	MYBPH	Q13203	984
AMT	DLD	P09622	900
AMT	SHMT2	P34897	727
AMT	SHMT1	P34896	709
AMT	A0A1W2PS29	A0A1W2PS29	691
AMT	A0A1W2PPQ1	A0A1W2PPQ1	673
AMT	GCAT	O75600	632
AMT	ATIC	P31939	589
AMT	AGXT	P21549	588
AMT	MTHFD1	P11586	585
AMT	OAT	P04181	559
AMT	MTHFR	P42898	558

IntAct

2 interactions, top by confidence:

A	B	Type	Score
	DNAJA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): AMT (Co-fractionation), PNPT1 (Co-fractionation), AMT (Two-hybrid), AMT (Two-hybrid), AMT (Affinity Capture-RNA), AMT (Affinity Capture-MS), AMT (Positive Genetic), AMT (Proximity Label-MS), AMT (Affinity Capture-Luminescence), AMT (Affinity Capture-MS)

ESM2 similar proteins: A2VD33, A5A6P1, A5GFY8, A6H791, A6QPU5, B5DEQ3, B8JMH0, D4AAT7, E1BNQ4, E2QUI9, O08651, O23936, O43175, O46504, O49849, O65396, P13439, P25285, P28337, P31754, P43353, P48728, P49363, P49364, P54260, P93256, P97849, Q2KI84, Q3KRD0, Q5EAD2, Q5R7M2, Q5R824, Q5XIG6, Q60HD7, Q61753, Q68FH4, Q6AY46, Q6PI48, Q7TNG8, Q7TSQ8

Diamond homologs: A0AIE9, A1BI02, A2CDX3, A4IQV5, A4J2F6, A4SDB4, A5GPL8, A5GWT1, A5IT65, A6GXW3, A6L6X5, A6L8T3, A6LP67, A6QH81, A6U208, A7FRV3, A7GB83, A7X2S3, A7Z6M4, A8MEG4, A9B2Q5, B0K242, B0KD95, B1IEV3, B1KWD5, B1XP99, B1YLN6, B2A2T4, B2FR21, B2RI74, B3EFX7, B3QLF1, B3QV24, B4S437, B4SED4, B4SSE0, B7GH71, B7K468, B8D1D7, B8DFY0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AMT	“form complex”	“Glycine cleavage system”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

774 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	61
Likely pathogenic	61
Uncertain significance	227
Likely benign	334
Benign	13

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069420	NM_000481.4(AMT):c.259-2A>C	Pathogenic
1070246	NM_000481.4(AMT):c.178C>T (p.Gln60Ter)	Pathogenic
1071338	NM_000481.4(AMT):c.2T>A (p.Met1Lys)	Pathogenic
1071418	NM_000481.4(AMT):c.317T>C (p.Ile106Thr)	Pathogenic
1071928	NM_000481.4(AMT):c.609dup (p.Phe204fs)	Pathogenic
1075196	NM_000481.4(AMT):c.257dup (p.Thr87fs)	Pathogenic
1076854	NM_001164710.2(AMT):c.340-552del	Pathogenic
11978	NM_000481.4(AMT):c.826G>C (p.Asp276His)	Pathogenic
11979	NM_000481.4(AMT):c.959G>A (p.Arg320His)	Pathogenic
11981	NM_000481.4(AMT):c.878-1G>A	Pathogenic
1398467	NM_000481.4(AMT):c.847C>T (p.Pro283Ser)	Pathogenic
1405893	NM_000481.4(AMT):c.221del (p.Gln74fs)	Pathogenic
1452651	NM_000481.4(AMT):c.819T>A (p.Tyr273Ter)	Pathogenic
1453525	NM_000481.4(AMT):c.59dup (p.Ala21fs)	Pathogenic
1455011	NC_000003.11:g.(?49454201)(49457785_?)del	Pathogenic
1457206	NM_000481.4(AMT):c.2T>C (p.Met1Thr)	Pathogenic
1804882	NM_000481.4(AMT):c.999_1000del (p.His333fs)	Pathogenic
1983641	NM_000481.4(AMT):c.965_966del (p.Gly322fs)	Pathogenic
2014596	NM_000481.4(AMT):c.931C>T (p.Gln311Ter)	Pathogenic
2043761	NM_000481.4(AMT):c.757del (p.Glu252_Val253insTer)	Pathogenic
2073847	NM_000481.4(AMT):c.10del (p.Ala4fs)	Pathogenic
208562	NM_000481.4(AMT):c.870G>A (p.Trp290Ter)	Pathogenic
2102638	NM_000481.4(AMT):c.74del (p.Pro25fs)	Pathogenic
2105835	NM_000481.4(AMT):c.1033+1G>A	Pathogenic
2131762	NM_000481.4(AMT):c.645_646del (p.Ser216fs)	Pathogenic
2203393	NM_000481.4(AMT):c.1101C>A (p.Cys367Ter)	Pathogenic
2705311	NM_000481.4(AMT):c.236_237del (p.Leu78_Phe79insTer)	Pathogenic
2734536	NM_000481.4(AMT):c.565C>T (p.Gln189Ter)	Pathogenic
2749793	NM_000481.4(AMT):c.815dup (p.Tyr273fs)	Pathogenic
2765422	NM_000481.4(AMT):c.1102G>T (p.Glu368Ter)	Pathogenic

SpliceAI

1481 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49417716:TACC:T	acceptor_loss	1.0000
3:49417717:ACC:A	acceptor_loss	1.0000
3:49417719:C:T	acceptor_loss	1.0000
3:49417720:T:G	acceptor_loss	1.0000
3:49417817:CCAAT:C	donor_gain	1.0000
3:49419275:T:A	donor_gain	1.0000
3:49421486:GCCCA:G	donor_loss	1.0000
3:49421487:CCCA:C	donor_loss	1.0000
3:49421488:CCAC:C	donor_loss	1.0000
3:49421489:CA:C	donor_loss	1.0000
3:49421490:A:AG	donor_loss	1.0000
3:49421506:G:C	donor_gain	1.0000
3:49421572:TC:T	acceptor_loss	1.0000
3:49421573:C:CA	acceptor_loss	1.0000
3:49421573:C:CC	acceptor_gain	1.0000
3:49422437:A:AC	donor_gain	1.0000
3:49422437:ACAG:A	donor_gain	1.0000
3:49422437:ACAGC:A	donor_gain	1.0000
3:49422438:C:CC	donor_gain	1.0000
3:49422438:CAG:C	donor_gain	1.0000
3:49422438:CAGC:C	donor_gain	1.0000
3:49422438:CAGCC:C	donor_gain	1.0000
3:49417715:GTAC:G	acceptor_gain	0.9900
3:49417716:TAC:T	acceptor_gain	0.9900
3:49417719:C:CC	acceptor_gain	0.9900
3:49417723:C:CT	acceptor_gain	0.9900
3:49417803:C:A	donor_gain	0.9900
3:49417974:C:CC	acceptor_gain	0.9900
3:49418965:GCTCA:G	donor_loss	0.9900
3:49418966:CTCAC:C	donor_loss	0.9900

AlphaMissense

2618 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49422206:A:C	F52L	0.997
3:49422206:A:T	F52L	0.997
3:49422208:A:G	F52L	0.997
3:49417705:A:C	S349R	0.995
3:49417705:A:T	S349R	0.995
3:49417707:T:G	S349R	0.995
3:49419059:G:C	S263R	0.995
3:49419059:G:T	S263R	0.995
3:49419061:T:G	S263R	0.995
3:49419283:A:G	Y225H	0.995
3:49419344:G:C	F204L	0.995
3:49419344:G:T	F204L	0.995
3:49419346:A:G	F204L	0.995
3:49420299:T:A	D128V	0.995
3:49422125:A:C	F79L	0.995
3:49422125:A:T	F79L	0.995
3:49422127:A:G	F79L	0.995
3:49417671:C:G	A361P	0.994
3:49420247:G:C	N145K	0.994
3:49420247:G:T	N145K	0.994
3:49419022:C:G	D276H	0.993
3:49419055:G:T	R265S	0.993
3:49420295:G:C	D129E	0.993
3:49420295:G:T	D129E	0.993
3:49420300:C:G	D128H	0.993
3:49419066:C:A	R261M	0.992
3:49420296:T:A	D129V	0.992
3:49420296:T:G	D129A	0.992
3:49420298:A:C	D128E	0.992
3:49420298:A:T	D128E	0.992

dbSNP variants (sampled 300 via entrez): RS1000159574 (3:49419945 A>G,T), RS1000277859 (3:49419602 A>G), RS1001144470 (3:49422591 A>T), RS1001350793 (3:49418743 G>A), RS1001504672 (3:49418753 C>T), RS1001561438 (3:49418010 T>C), RS1002078582 (3:49423496 C>T), RS1002403564 (3:49424230 A>G), RS1004302454 (3:49416277 C>T), RS1004875097 (3:49419127 C>G,T), RS1005010761 (3:49418667 A>G), RS1005423765 (3:49418647 G>A), RS1005696176 (3:49424193 G>A), RS1006246329 (3:49423909 T>C), RS1006290394 (3:49417308 G>A,T)

Disease associations

OMIM: gene MIM:238310 | disease phenotypes: MIM:605899, MIM:620398, MIM:212138, MIM:613818, MIM:616538

GenCC curated gene-disease

Disease	Classification	Inheritance
glycine encephalopathy	Definitive	Autosomal recessive
glycine encephalopathy 2	Definitive	Autosomal recessive
glycine encephalopathy 1	Strong	Autosomal recessive
neonatal glycine encephalopathy	Supportive	Autosomal recessive
infantile glycine encephalopathy	Supportive	Autosomal recessive
atypical glycine encephalopathy	Supportive	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glycine encephalopathy	Definitive	AR

Mondo (9): glycine encephalopathy (MONDO:0011612), glycine encephalopathy 2 (MONDO:0958192), glycine encephalopathy 1 (MONDO:0958179), carnitine-acylcarnitine translocase deficiency (MONDO:0008918), autosomal recessive limb-girdle muscular dystrophy type 2P (MONDO:0013440), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (MONDO:0014683), neonatal glycine encephalopathy (MONDO:0017353), infantile glycine encephalopathy (MONDO:0017354), atypical glycine encephalopathy (MONDO:0015010)

Orphanet (5): Glycine encephalopathy (Orphanet:407), Carnitine-acylcarnitine translocase deficiency (Orphanet:159), Alpha-dystroglycan-related limb-girdle muscular dystrophy R16 (Orphanet:280333), Muscle-eye-brain disease with bilateral multicystic leucodystrophy (Orphanet:370997), Walker-Warburg syndrome (Orphanet:899)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0002878	Respiratory failure
HP:0003623	Neonatal onset
HP:0008288	Nonketotic hyperglycinemia
HP:0010851	EEG with burst suppression
HP:0010864	Severe intellectual disability
HP:0011342	Mild global developmental delay
HP:0011463	Childhood onset
HP:0500230	Increased CSF glycine concentration

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002774_6	Cognitive function	8.000000e-06
GCST003854_53	Gut microbiota (functional units)	4.000000e-06
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005196_105	Coronary artery disease	1.000000e-08
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST008840_1	Depressive symptom (depressed mood) (binary trait)	8.000000e-10
GCST008849_2	Depressive symptoms (binary sum-score)	7.000000e-09
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0007874	gut microbiome measurement
EFO:0009592	social interaction measurement
EFO:0007006	depressive symptom measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562812	Carnitine-Acylcarnitine Translocase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	2
Fluorouracil	increases expression	2
Nickel	decreases expression	2
Valproic Acid	affects expression, increases expression	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
methylselenic acid	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Plant Oils	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Quercetin	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

6 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02214160	PHASE2	COMPLETED	Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments