GCAT

Summary

GCAT (glycine C-acetyltransferase, HGNC:4188) is a protein-coding gene on chromosome 22q13.1, encoding 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial (O75600). Pyridoxal phosphate (PLP) dependent enzyme, which catalyzes the cleavage of 2-amino-3-oxobutanoate to glycine and acetyl-CoA.

The degradation of L-threonine to glycine consists of a two-step biochemical pathway involving the enzymes L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. L-Threonine is first converted into 2-amino-3-ketobutyrate by L-threonine dehydrogenase. This gene encodes the second enzyme in this pathway, which then catalyzes the reaction between 2-amino-3-ketobutyrate and coenzyme A to form glycine and acetyl-CoA. The encoded enzyme is considered a class II pyridoxal-phosphate-dependent aminotransferase. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 14.

Source: NCBI Gene 23464 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_014291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4188
Approved symbol	GCAT
Name	glycine C-acetyltransferase
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	KBL
Ensembl gene	ENSG00000100116
Ensembl biotype	protein_coding
OMIM	607422
Entrez	23464

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 22 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000248924, ENST00000323205, ENST00000415371, ENST00000426858, ENST00000445195, ENST00000451984, ENST00000478203, ENST00000892357, ENST00000892358, ENST00000892359, ENST00000892360, ENST00000892361, ENST00000892362, ENST00000892363, ENST00000892364, ENST00000892365, ENST00000892366, ENST00000892367, ENST00000892368, ENST00000892369, ENST00000892370, ENST00000912827, ENST00000912828, ENST00000945451, ENST00000945452

RefSeq mRNA: 2 — MANE Select: NM_014291 NM_001171690, NM_014291

CCDS: CCDS13957, CCDS54527

Canonical transcript exons

ENST00000248924 — 9 exons

Exon	Start	End
ENSE00000654026	37815126	37815280
ENSE00000654041	37815418	37815500
ENSE00000654050	37815663	37815834
ENSE00000880223	37816200	37816321
ENSE00001351315	37816567	37816897
ENSE00001862442	37807934	37808163
ENSE00003504293	37813463	37813609
ENSE00003534514	37812887	37812988
ENSE00003617410	37810027	37810157

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 95.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9029 / max 145.9400, expressed in 1640 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192203	11.5749	1636
192204	0.3280	143

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.03	gold quality
apex of heart	UBERON:0002098	93.88	gold quality
right lobe of liver	UBERON:0001114	93.15	gold quality
heart left ventricle	UBERON:0002084	91.37	gold quality
cardiac ventricle	UBERON:0002082	91.04	gold quality
oocyte	CL:0000023	89.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.61	gold quality
liver	UBERON:0002107	88.72	gold quality
buccal mucosa cell	CL:0002336	87.99	gold quality
endothelial cell	CL:0000115	87.67	gold quality
right frontal lobe	UBERON:0002810	87.60	gold quality
prefrontal cortex	UBERON:0000451	87.36	gold quality
pancreas	UBERON:0001264	86.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.68	gold quality
heart	UBERON:0000948	86.64	gold quality
cerebellar hemisphere	UBERON:0002245	85.97	gold quality
amygdala	UBERON:0001876	85.80	gold quality
cerebellar cortex	UBERON:0002129	85.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.70	gold quality
nucleus accumbens	UBERON:0001882	85.68	gold quality
cingulate cortex	UBERON:0003027	85.51	gold quality
anterior cingulate cortex	UBERON:0009835	85.22	gold quality
right atrium auricular region	UBERON:0006631	85.18	gold quality
mucosa of transverse colon	UBERON:0004991	85.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.10	gold quality
frontal cortex	UBERON:0001870	85.03	gold quality
gastrocnemius	UBERON:0001388	85.00	gold quality
heart right ventricle	UBERON:0002080	84.96	gold quality
putamen	UBERON:0001874	84.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• effect of gene on proliferation arrest in a non-small cell bronchopulmonary cancer line. (PMID:12174908)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gcat	ENSDARG00000005643
mus_musculus	Gcat	ENSMUSG00000006378
rattus_norvegicus	Gcat	ENSRNOG00000055408
drosophila_melanogaster	Gcat	FBGN0036208
caenorhabditis_elegans		WBGENE00012007

Paralogs (5): ALAS1 (ENSG00000023330), SPTLC1 (ENSG00000090054), SPTLC2 (ENSG00000100596), ALAS2 (ENSG00000158578), SPTLC3 (ENSG00000172296)

Protein

Protein identifiers

2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial — O75600 (reviewed: O75600)

Alternative names: Aminoacetone synthase, Glycine acetyltransferase

All UniProt accessions (4): O75600, C9IZC9, F2Z340, H7BZ75

UniProt curated annotations — full annotation on UniProt →

Function. Pyridoxal phosphate (PLP) dependent enzyme, which catalyzes the cleavage of 2-amino-3-oxobutanoate to glycine and acetyl-CoA.

Subcellular location. Mitochondrion. Nucleus.

Tissue specificity. Strongly expressed in heart, brain, liver and pancreas. Also found in lung.

Similarity. Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75600-1	1	yes
O75600-2	2

RefSeq proteins (2): NP_001165161, NP_055106* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001917	Aminotrans_II_pyridoxalP_BS	Binding_site
IPR004839	Aminotransferase_I/II_large	Domain
IPR011282	2am3keto_CoA_ligase	Family
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR050087	AON_synthase_class-II	Family

Pfam: PF00155

Catalyzed reactions (Rhea), 1 shown:

• glycine + acetyl-CoA = (2S)-2-amino-3-oxobutanoate + CoA (RHEA:20736)

UniProt features (22 total): modified residue 9, binding site 6, sequence variant 2, sequence conflict 2, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75600-F1	93.23	0.87

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 (6): 134–135 (in other chain); 159; 206 (in other chain); 262–265 (in other chain); 295–296; 389

Post-translational modifications (9): 187, 187, 265, 326, 368, 383, 383, 45, 45

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-8849175	Threonine catabolism

MSigDB gene sets: 156 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, PAL_PRMT5_TARGETS_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, CAGCTG_AP4_Q5, GOLDRATH_ANTIGEN_RESPONSE, MODULE_285, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, DELYS_THYROID_CANCER_DN, TGIF_01, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, AACTTT_UNKNOWN, MYB_Q3

GO Biological Process (3): amino acid metabolic process (GO:0006520), L-threonine catabolic process (GO:0006567), biosynthetic process (GO:0009058)

GO Molecular Function (4): glycine C-acetyltransferase activity (GO:0008890), pyridoxal phosphate binding (GO:0030170), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), nuclear speck (GO:0016607), cytoplasm (GO:0005737), mitochondrial inner membrane (GO:0005743)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism	1
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
primary metabolic process	1
L-threonine metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
metabolic process	1
C-acetyltransferase activity	1
amino acid acyltransferase activity	1
anion binding	1
vitamin B6 binding	1
catalytic activity	1
transferase activity	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular anatomical structure	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

1596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCAT	GALR3	O60755	900
GCAT	H1-0	P07305	650
GCAT	AMT	P48728	632
GCAT	SPMIP1	A0A1B0GUX0	593
GCAT	SHMT2	P34897	571
GCAT	GLDC	P23378	568
GCAT	PSAT1	Q9Y617	477
GCAT	NDUFAF3	Q9BU61	476
GCAT	GPKOW	Q92917	475
GCAT	SDS	P20132	435
GCAT	ATP10D	Q9P241	427
GCAT	OSGEP	Q9NPF4	422
GCAT	SDSL	Q96GA7	421
GCAT	GCSH	P23434	414
GCAT	H7C2H4	H7C2H4	407

IntAct

32 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
GCAT	NDUFS6	psi-mi:“MI:0914”(association)	0.530
MDM2	GCAT	psi-mi:“MI:0915”(physical association)	0.370
TEAD1	GCAT	psi-mi:“MI:0915”(physical association)	0.370
ECSIT	NDUFS2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
GCAT	BCKDK	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CA10	ENTPD5	psi-mi:“MI:0914”(association)	0.350
DNAJA2	ENC1	psi-mi:“MI:0914”(association)	0.350
FPR1	NBAS	psi-mi:“MI:0914”(association)	0.350
TUBB	VWA8	psi-mi:“MI:0914”(association)	0.350
SLC37A3	PLXNB2	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350
STAT3	HAX1	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (69): CLPX (Affinity Capture-MS), LONP1 (Affinity Capture-MS), MCCC1 (Affinity Capture-MS), EMB (Affinity Capture-MS), NDUFS6 (Affinity Capture-MS), GCAT (Affinity Capture-MS), GCAT (Affinity Capture-MS), EMB (Affinity Capture-MS), LONP1 (Affinity Capture-MS), NDUFS6 (Affinity Capture-MS), MCCC1 (Affinity Capture-MS), GCAT (Affinity Capture-MS), GCAT (Affinity Capture-MS), GCAT (Proximity Label-MS), GCAT (Affinity Capture-MS)

ESM2 similar proteins: A2VDS1, A4SP14, A4VNY2, A4XY43, A5GFY8, A6V0U8, A7H804, A7MBC0, A8GHY3, B0VD51, B0VNW2, B0YLW6, B2HZI5, B4UCP2, B7H3H0, B7I5Q3, B7UWH7, B8JC53, C1DE68, O31269, O43175, O49543, O60028, O74351, O75600, O88986, P0DN31, P25374, Q02RW8, Q0P5L8, Q10G56, Q1H361, Q2INI7, Q5BJY6, Q5R7M2, Q5U4Q9, Q60HD7, Q61753, Q66IQ6, Q68FT9

Diamond homologs: A0RIB9, A1AQT1, A1K6Q1, A1U4B1, A3DBD5, A4G5N9, A5G6I9, A5VXF2, A6LMP4, A6TU88, A7BFV6, A7BFV7, A7BFV8, A7GSE1, A7HG96, A7HMM1, A7LXM2, A7Z4X1, A7Z5B4, A8FDG9, A8MEX7, A9BGL0, A9VG56, B0C205, B0K590, B0KC20, B0KJ54, B1JE54, B1XL23, B1YMC6, B2J1W1, B3EAE0, B4UCB1, B5EEV8, B5Y9Z4, B5YFU5, B7GHW7, B7HAZ0, B7HNN4, B7ID58

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex I biogenesis	5	29.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1570 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37808159:CGGAG:C	donor_loss	1.0000
22:37808161:G:GT	donor_gain	1.0000
22:37808163:GGTA:G	donor_loss	1.0000
22:37808164:G:T	donor_loss	1.0000
22:37808165:T:G	donor_loss	1.0000
22:37812885:A:AG	acceptor_gain	1.0000
22:37812886:G:GT	acceptor_gain	1.0000
22:37812886:GA:G	acceptor_gain	1.0000
22:37812886:GAGC:G	acceptor_gain	1.0000
22:37812886:GAGCA:G	acceptor_gain	1.0000
22:37812987:AG:A	donor_loss	1.0000
22:37812990:T:A	donor_loss	1.0000
22:37813458:TCCA:T	acceptor_loss	1.0000
22:37813459:CCAG:C	acceptor_loss	1.0000
22:37813460:CA:C	acceptor_loss	1.0000
22:37813461:A:AG	acceptor_gain	1.0000
22:37813461:A:G	acceptor_loss	1.0000
22:37813462:G:GG	acceptor_gain	1.0000
22:37813586:G:GT	donor_gain	1.0000
22:37813601:G:GT	donor_gain	1.0000
22:37813605:CCCAG:C	donor_loss	1.0000
22:37813606:CCAG:C	donor_loss	1.0000
22:37813607:CAGG:C	donor_loss	1.0000
22:37813609:GGT:G	donor_loss	1.0000
22:37813610:G:C	donor_loss	1.0000
22:37813654:G:GT	donor_gain	1.0000
22:37815124:A:AG	acceptor_gain	1.0000
22:37815125:G:GG	acceptor_gain	1.0000
22:37815125:GAA:G	acceptor_gain	1.0000
22:37815125:GAAGC:G	acceptor_gain	1.0000

AlphaMissense

2701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37815162:T:C	F205L	0.996
22:37815164:T:A	F205L	0.996
22:37815164:T:G	F205L	0.996
22:37810049:C:A	N73K	0.995
22:37810049:C:G	N73K	0.995
22:37815728:T:C	F294L	0.995
22:37815730:C:A	F294L	0.995
22:37815730:C:G	F294L	0.995
22:37812961:T:G	C134W	0.994
22:37810037:C:A	N69K	0.993
22:37810037:C:G	N69K	0.993
22:37813507:C:A	N158K	0.993
22:37813507:C:G	N158K	0.993
22:37813510:T:A	H159Q	0.992
22:37813510:T:G	H159Q	0.992
22:37815248:C:G	C233W	0.992
22:37810052:C:A	N74K	0.991
22:37810052:C:G	N74K	0.991
22:37810128:A:C	S100R	0.991
22:37810130:C:A	S100R	0.991
22:37810130:C:G	S100R	0.991
22:37810043:T:G	C71W	0.990
22:37815240:G:C	D231H	0.989
22:37816229:T:C	F339S	0.989
22:37816576:T:A	V373D	0.989
22:37816584:T:C	F376L	0.989
22:37816586:C:A	F376L	0.989
22:37816586:C:G	F376L	0.989
22:37816618:G:C	R387P	0.989
22:37812956:A:C	S133R	0.988

dbSNP variants (sampled 300 via entrez): RS1000240010 (22:37810896 T>G), RS1000345223 (22:37807542 A>G), RS1000725558 (22:37807967 G>A), RS1000766585 (22:37813720 A>G), RS1000821512 (22:37811303 C>A,T), RS1001438227 (22:37811515 C>T), RS1001637480 (22:37811954 G>C), RS1001838698 (22:37807020 C>T), RS1002046648 (22:37816840 C>T), RS1002386930 (22:37812984 T>C), RS1002437910 (22:37812760 A>C,G), RS1002719606 (22:37817423 C>T), RS1002781131 (22:37807028 G>A,T), RS1002794176 (22:37807279 C>G), RS1002929663 (22:37815636 TC>T,TCC)

Disease associations

OMIM: gene MIM:607422 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10
GCST90002392_223	Mean corpuscular volume	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
sodium arsenite	increases expression, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
trichostatin A	decreases expression	1
avobenzone	increases expression	1
entinostat	decreases expression	1
K 7174	decreases expression	1
belinostat	decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
ortho-topolin riboside	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Melatonin	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Fenofibrate	decreases expression	1
Selenium	increases expression	1

Clinical trials (associated diseases)

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