AMT (aminomethyltransferase)

Gene

• Entrez ID: 275
• Gene name: Aminomethyltransferase
• Gene symbol: AMT
• Synonyms (NCBI Gene): GCE, GCE2, GCST, GCVT, NKH
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: 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. [provided by

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1126422	G>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs116192290	C>G,T	Conflicting-interpretations-of-pathogenicity, benign-likely-benign	Non coding transcript variant, missense variant, coding sequence variant
rs121964981	C>T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs121964984	C>G	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs121964985	C>A,T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs121964986	G>A	Likely-pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs181134220	C>G,T	Pathogenic	Splice acceptor variant
rs386833681	C>G	Likely-pathogenic	Splice acceptor variant
rs386833682	T>A,C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant, intron variant
rs386833683	GAGGGCCAAATCTTT>-	Pathogenic	Non coding transcript variant, coding sequence variant, inframe deletion, intron variant
rs386833684	A>G	Pathogenic	Splice donor variant, intron variant
rs386833685	G>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs386833689	T>C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs386833690	C>T	Uncertain-significance, pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs386833691	TCA>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, inframe deletion
rs386833692	GC>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs541594122	A>C,T	Likely-pathogenic	Splice donor variant
rs558998633	G>A	Likely-pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs753221440	C>A,T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs757918826	C>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs781466698	G>A	Pathogenic-likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs797045082	C>T	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs866625610	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant
rs1056820947	G>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1238918084	->C	Likely-pathogenic	Splice acceptor variant, non coding transcript variant, coding sequence variant
rs1278265933	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1553638247	A>G	Pathogenic	Splice donor variant
rs1553638266	C>-,CC	Pathogenic-likely-pathogenic, likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1553638405	A>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1553638408	->A	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1553638457	CTTCTTGACACACCTCCACACCA>-	Likely-pathogenic	Splice donor variant, non coding transcript variant, intron variant, coding sequence variant
rs1553638460	C>T	Likely-pathogenic	Splice donor variant
rs1553638649	CA>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, intron variant, coding sequence variant
rs1575303218	G>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1575305901	C>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1575308129	C>T	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018253	hsa-miR-335-5p	Microarray	18185580
MIRT780659	hsa-miR-1	CLIP-seq
MIRT780660	hsa-miR-185	CLIP-seq
MIRT780661	hsa-miR-206	CLIP-seq
MIRT780662	hsa-miR-3065-3p	CLIP-seq
MIRT780663	hsa-miR-3190	CLIP-seq
MIRT780664	hsa-miR-4306	CLIP-seq
MIRT780665	hsa-miR-4481	CLIP-seq
MIRT780666	hsa-miR-4491	CLIP-seq
MIRT780667	hsa-miR-4644	CLIP-seq
MIRT780668	hsa-miR-4657	CLIP-seq
MIRT780669	hsa-miR-4745-5p	CLIP-seq
MIRT780670	hsa-miR-613	CLIP-seq
MIRT780671	hsa-miR-7	CLIP-seq
MIRT780672	hsa-miR-759	CLIP-seq
MIRT780662	hsa-miR-3065-3p	CLIP-seq
MIRT1930447	hsa-miR-3121-5p	CLIP-seq
MIRT2384146	hsa-miR-4710	CLIP-seq
MIRT2384147	hsa-miR-4792	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004047	Function	Aminomethyltransferase activity	IEA
GO:0004047	Function	Aminomethyltransferase activity	IMP	16051266
GO:0004047	Function	Aminomethyltransferase activity	TAS
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005654	Component	Nucleoplasm	IDA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IC	16051266
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	TAS	8188235
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005960	Component	Glycine cleavage complex	IEA
GO:0006546	Process	Glycine catabolic process	IEA
GO:0006546	Process	Glycine catabolic process	TAS	9600239
GO:0008483	Function	Transaminase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0019464	Process	Glycine decarboxylation via glycine cleavage system	IMP	16051266

Other IDs

• MIM: 238310
• HGNC: 473
• e!Ensembl: ENSG00000145020

Protein

• UniProt ID: P48728
• Protein name: Aminomethyltransferase, mitochondrial (EC 2.1.2.10) (Glycine cleavage system T protein) (GCVT)
• Protein function: The glycine cleavage system catalyzes the degradation of glycine.
• PDB: 1WSR, 1WSV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01571	GCV_T	38 → 291	Aminomethyltransferase folate-binding domain	Domain
  PF08669	GCV_T_C	318 → 396	Glycine cleavage T-protein C-terminal barrel domain	Domain

• Sequence:

  MQRAVSVVARLGFRLQAFPPALCRPLSCAQEVLRRTPLYDFHLAHGGKMVAFAGWSLPVQ
  YRDSHTDSHLHTRQHCSLFDVSHMLQTKILGSDRVKLMESLVVGDIAELRPNQGTLSLFT
  NEAGGILDDLIVTNTSEGHLYVVSNAGCWEKDLALMQDKVRELQNQGRDVGLEVLDNALL
  ALQGPTAAQVLQAGVADDLRKLPFMTSAVMEVFGVSGCRVTRCGYTGEDGVEISVPVAGA
  VHLATAILKNPEVKLAGLAARDSLRLEAGLCLYGNDIDEHTTPVEGSLSWTLGKRRRAAM
  DFPGAKVIVPQLKGRVQRRRVGLMCEGAPMRAHSPILNMEGTKIGTVTSGCPSPSLKKNV
  AMGYVPCEYSRPGTMLLVEVRRKQQMAVVSKMPFVPTNYYTLK

• Sequence length: 403

Pathways

KEGG:

Glycine, serine and threonine metabolism
Glyoxylate and dicarboxylate metabolism
One carbon pool by folate
Lipoic acid metabolism
Metabolic pathways
Carbon metabolism

Reactome:

Glycine degradation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Glycine encephalopathy	Pathogenic; Likely pathogenic	rs1279743247, rs1352631535, rs562695274, rs1266259634, rs2107932226, rs2107933839, rs1249645541, rs748522054, rs2107937267, rs2107937536, rs2107937574, rs2049058298, rs2107933731, rs2107933735, rs386833680, rs2107937352, rs386833690, rs2107931458, rs2107935989, rs386833686, rs771214835, rs781466698, rs2107937370, rs2049124862, rs2471146082, rs541011963, rs2471150599, rs753150990, rs386833685, rs2471154253, rs2049026547, rs797045082, rs2471161355, rs1056820947, rs2471146370, rs2471150370, rs2471162355, rs1167886830, rs1210592462, rs2107928969, rs2471161813, rs2471151168, rs2471145430, rs2471158020, rs121964983, rs121964984, rs121964985, rs121964986, rs181134220, rs2471146274, rs2471161209, rs2471154458, rs2471146213, rs2471145466, rs2471160480, rs1039165645, rs2049060862, rs2471150164, rs2471145574, rs373140736, rs2471151025, rs2471150314, rs2471160357, rs2107932045, rs2471158260, rs2471150601, rs2471145374, rs1171965250, rs386833679, rs2471160420, rs1467607949, rs769468125, rs1553638907, rs1553638463, rs541594122, rs1553638457, rs1053797603, rs1553638266, rs558998633, rs1126422, rs1553638904, rs753743263, rs757918826, rs779483959, rs1553638247, rs866625610, rs1483890972, rs1553638822, rs1559530507, rs773988915, rs1575309867, rs1575308888, rs1575308129, rs121964982, rs386833678, rs386833681, rs386833682, rs386833683, rs386833684, rs386833687, rs386833688, rs386833689, rs386833692, rs1575303218, rs1575305901, rs1278265933, rs2049052992, rs2049020585, rs2049022161, rs2049025668, rs2049123051, rs1368099067, rs768293167	RCV001312233 RCV001329302 RCV001329301 RCV001972587 RCV001384518 RCV001390880 RCV001383889 RCV001381284 RCV001388721 RCV001382319 RCV001385076 RCV001383790 RCV003470848 RCV001806813 RCV001825146 RCV001844504 RCV001870436 RCV001968995 RCV002037709 RCV002001336 RCV002002454 RCV001915076 RCV001961638 RCV001935293 RCV002011866 RCV002471300 RCV003087006 RCV002624512 RCV002664312 RCV002651706 RCV002750240 RCV002756630 RCV000190566 RCV002814674 RCV002829439 RCV002830118 RCV002913231 RCV002944167 RCV002972569 RCV003019611 RCV003023656 RCV003063840 RCV003036415 RCV003142289 RCV003147203 RCV000012756 RCV000012758 RCV000012759 RCV000012760 RCV000012761 RCV003331830 RCV003461882 RCV003461884 RCV003470219 RCV003461890 RCV003512917 RCV003513590 RCV003513592 RCV003511688 RCV003512653 RCV003512607 RCV003625227 RCV003625255 RCV003625368 RCV003625464 RCV003625426 RCV003625468 RCV003625915 RCV003625984 RCV003624969 RCV003830821 RCV003856526 RCV000495928 RCV002525127 RCV000533799 RCV000638279 RCV000670825 RCV000666301 RCV000673332 RCV000668200 RCV000673783 RCV000674000 RCV000667775 RCV000671316 RCV000669862 RCV000665764 RCV000672693 RCV000666875 RCV000672268 RCV000668737 RCV000666927 RCV000685122 RCV001868952 RCV000761472 RCV000813481 RCV000817660 RCV000806703 RCV000049638 RCV000049639 RCV000049641 RCV000049642 RCV000049643 RCV000049644 RCV000049645 RCV000049646 RCV000049647 RCV000049648 RCV000049649 RCV000049650 RCV000049651 RCV000049653 RCV000987270 RCV000987271 RCV002505520 RCV001056489 RCV001236819 RCV001226600 RCV001244920 RCV001239628 RCV001257431 RCV001305807	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glycine encephalopathy 1	Pathogenic; Likely pathogenic	rs2049124862, rs121964983, rs121964984, rs121964985, rs121964986, rs181134220, rs748522054, rs2471158260, rs2049119534, rs769468125, rs1553638405, rs1553638457, rs1553638460, rs1053797603, rs1238918084, rs1553638266, rs1553638408, rs781466698, rs558998633, rs1126422, rs1553638904, rs753743263, rs757918826, rs779483959, rs1553638206, rs1553638247, rs866625610, rs1553638649, rs1483890972, rs1553638822, rs773988915, rs1056820947, rs386833680, rs386833682, rs386833683, rs386833684, rs386833690, rs2049020585	RCV004571689 RCV004566726 RCV005430459 RCV004566727 RCV004566728 RCV004566729 RCV004574038 RCV004574273 RCV004576230 RCV005430541 RCV005430585 RCV005430683 RCV005430392 RCV004568499 RCV005430564 RCV005430764 RCV005430798 RCV004568513 RCV005430777 RCV004568563 RCV005430576 RCV005430699 RCV005430637 RCV005430421 RCV004568549 RCV005430446 RCV005430450 RCV005430726 RCV005430802 RCV004568518 RCV005430454 RCV004576965 RCV004569693 RCV004566904 RCV004566905 RCV004566906 RCV005430478 RCV005430479 RCV004570598	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glycine encephalopathy 2	Pathogenic; Likely pathogenic	rs1279743247, rs1352631535, rs2107937574, rs2107932966, rs2107938475, rs2107937352, rs2471150599, rs2471158020, rs121964983, rs121964984, rs121964985, rs121964986, rs181134220, rs2471160420, rs769468125, rs1053797603, rs781466698, rs1126422, rs757918826, rs779483959, rs866625610, rs773988915, rs386833682, rs386833683, rs386833684, rs386833686, rs2049020585, rs2049025668	RCV003888014 RCV005911078 RCV005038192 RCV003492272 RCV003492273 RCV005023306 RCV005034800 RCV003492842 RCV003230355 RCV003230356 RCV003230357 RCV003230358 RCV003230359 RCV005230588 RCV003230522 RCV005027783 RCV005004333 RCV005860124 RCV003492125 RCV005027817 RCV003492126 RCV005231306 RCV005025098 RCV003492394 RCV005025099 RCV003230387 RCV005036515 RCV004570624	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neurodevelopmental delay	Likely pathogenic; Pathogenic	rs386833683	RCV002273950	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AMT-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATYPICAL GLYCINE ENCEPHALOPATHY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLYCINE ENCEPHALOPATHY WITH NORMAL SERUM GLYCINE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERGLYCINEMIA, NONKETOTIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atypical glycine encephalopathy	Glycine Encephalopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	23352163		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	25667121		★☆☆☆☆ Found in Text Mining only
Corneal Ulcer	Corneal Ulcer	BEFREE	29456673		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	GWASDB_DG	17804789		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	29723235		★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	BEFREE	21421655		★☆☆☆☆ Found in Text Mining only
Early myoclonic encephalopathy	Myoclonic Encephalopathy	BEFREE	26371980		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	10822440		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	BEFREE	30742989		★☆☆☆☆ Found in Text Mining only
Hemophilia B	Hemophilia	BEFREE	31698454, 31709273		★☆☆☆☆ Found in Text Mining only
Hyperglycinemia Nonketotic	Hyperglycemia	Pubtator	19299230, 27164344, 27362913	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycinemia, Nonketotic, Type I	Hyperglycinemia	CTD_human_DG	16450403		★☆☆☆☆ Found in Text Mining only
Hyperglycinemia, Nonketotic, Type II	Hyperglycinemia	CTD_human_DG	16450403		★☆☆☆☆ Found in Text Mining only
Hyperglycinemia, Nonketotic, Type III	Hyperglycinemia	CTD_human_DG	16450403		★☆☆☆☆ Found in Text Mining only
HYPERGLYCINURIA (disorder)	Hyperglycinuria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperlipoproteinemia Type I	Hyperlipoproteinemia	BEFREE	22717743, 25559420		★☆☆☆☆ Found in Text Mining only
Infantile glycine encephalopathy	Glycine Encephalopathy	Orphanet			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	33819484	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	7532919		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28529635		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	29723235		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	31230217		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	30412738		★☆☆☆☆ Found in Text Mining only
Nasal Polyps	Nasal polyposis	BEFREE	18329792		★☆☆☆☆ Found in Text Mining only
Neonatal glycine encephalopathy	Glycine Encephalopathy	Orphanet			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	25667121		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural tube defect	Pubtator	27620832	Associate	★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	29232014		★☆☆☆☆ Found in Text Mining only
Nonketotic Hyperglycinemia	Nonketotic Hyperglycinemia	CLINVAR_DG	10873393, 11139253, 12948742, 15272469, 16051266, 16450403, 22261077, 23352163, 25231368, 26179960, 27164344, 27362913, 28244183, 29300369, 8005589, 9621520		★☆☆☆☆ Found in Text Mining only
Nonketotic Hyperglycinemia	Nonketotic Hyperglycinemia	UNIPROT_DG	10873393, 11286506, 16051266, 26371980, 28244183, 8005589, 9600239, 9621520		★☆☆☆☆ Found in Text Mining only
Nonketotic Hyperglycinemia	Nonketotic Hyperglycinemia	BEFREE	11139253, 1634607, 16450403, 1695480, 17361008, 2013671, 25231368, 26371980, 27362913, 27481395, 29300369, 30108280, 30350008, 31230217, 8657542, 9600239		★☆☆☆☆ Found in Text Mining only
Nonketotic Hyperglycinemia	Nonketotic Hyperglycinemia	CTD_human_DG	16450403		★☆☆☆☆ Found in Text Mining only
Nonketotic Hyperglycinemia	Nonketotic Hyperglycinemia	CLINGEN_DG	25231368, 26179960, 26371980, 27164344, 6469978, 6863283, 8005589		★☆☆☆☆ Found in Text Mining only
Nonketotic Hyperglycinemia	Nonketotic Hyperglycinemia	GENOMICS_ENGLAND_DG	27604308		★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	BEFREE	22717743, 25559420		★☆☆☆☆ Found in Text Mining only
Russell-Silver syndrome	Russell-Silver Syndrome	BEFREE	20082469		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	29232014	Associate	★☆☆☆☆ Found in Text Mining only
Spasms Infantile	Infantile spasms	Pubtator	19299230	Associate	★☆☆☆☆ Found in Text Mining only