GLYAT

Summary

GLYAT (glycine-N-acyltransferase, HGNC:13734) is a protein-coding gene on chromosome 11q12.1, encoding Glycine N-acyltransferase (Q6IB77). Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently.

The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria. The protein is thought to be important in the detoxification of endogenous and xenobiotic acyl-CoA’s. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10249 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_201648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13734
Approved symbol	GLYAT
Name	glycine-N-acyltransferase
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	GAT, ACGNAT
Ensembl gene	ENSG00000149124
Ensembl biotype	protein_coding
OMIM	607424
Entrez	10249

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000278400, ENST00000344743, ENST00000529732, ENST00000531084, ENST00000586098, ENST00000611865

RefSeq mRNA: 2 — MANE Select: NM_201648 NM_005838, NM_201648

CCDS: CCDS7970, CCDS7971

Canonical transcript exons

ENST00000344743 — 6 exons

Exon	Start	End
ENSE00000988914	58724416	58724511
ENSE00000988915	58715316	58715423
ENSE00000988916	58712760	58712886
ENSE00001382341	58708757	58710168
ENSE00001384131	58710590	58710761
ENSE00002147597	58731835	58731943

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 97.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7952 / max 490.0055, expressed in 39 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119827	1.4352	29
119831	0.1859	20
119829	0.0865	14
119828	0.0583	16
119830	0.0292	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.85	gold quality
nephron tubule	UBERON:0001231	97.55	gold quality
adult mammalian kidney	UBERON:0000082	97.27	gold quality
kidney epithelium	UBERON:0004819	96.63	gold quality
renal glomerulus	UBERON:0000074	95.39	gold quality
liver	UBERON:0002107	94.60	gold quality
metanephric glomerulus	UBERON:0004736	94.59	gold quality
kidney	UBERON:0002113	93.41	gold quality
adult organism	UBERON:0007023	90.72	gold quality
cortex of kidney	UBERON:0001225	90.04	gold quality
renal medulla	UBERON:0000362	86.32	gold quality
metanephros	UBERON:0000081	83.83	gold quality
metanephros cortex	UBERON:0010533	82.69	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.86	gold quality
adipose tissue	UBERON:0001013	78.85	gold quality
connective tissue	UBERON:0002384	76.94	gold quality
cervix squamous epithelium	UBERON:0006922	74.32	gold quality
sural nerve	UBERON:0015488	71.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	70.03	gold quality
tibialis anterior	UBERON:0001385	69.81	silver quality
thoracic mammary gland	UBERON:0005200	69.15	gold quality
mammary gland	UBERON:0001911	69.07	gold quality
omental fat pad	UBERON:0010414	68.78	gold quality
peritoneum	UBERON:0002358	68.70	gold quality
tibial nerve	UBERON:0001323	66.86	gold quality
mammary duct	UBERON:0001765	63.86	silver quality
tongue squamous epithelium	UBERON:0006919	63.80	gold quality
epithelium of mammary gland	UBERON:0003244	63.54	silver quality
diaphragm	UBERON:0001103	63.32	gold quality
cervix epithelium	UBERON:0004801	63.08	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	65.68
E-HCAD-10	yes	38.52
E-MTAB-10553	yes	30.27
E-ANND-3	yes	12.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SREBF1

miRNA regulators (miRDB)

47 targeting GLYAT, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517

Literature-anchored findings (GeneRIF, showing 8)

• The aim of this work was to report a comprehensive investigation of GLYAT genetic polymorphisms in DNA samples from 55 subjects of French Caucasian origin. (PMID:20925583)
• hGLYAT is a good candidate as a novel marker of hepatocellular carcinoma and may be a key molecule in the transition between differentiation and carcinogenesis of liver cells. (PMID:22475485)
• We identify GLYAT gene which appears to co-regulate bone size phenotypes (BSPs) and appendicular lean mass (ALM). (PMID:23108985)
• SNP variations causing amino acid substitutions in the human GLYAT gene influence the kinetic properties of the enzyme. (PMID:23237781)
• Data indicate that Afrikaner caucasians have a Q61L single nucleotide polymorphism (SNP) occurring at a high frequency (12%). (PMID:26149650)
• GLYAT exhibits mechanistic kinetic cooperativity towards its substrate glycine. (PMID:28759163)
• Frequent sequence variants of human glycine N-acyltransferase (GLYAT) and inborn errors of metabolism. (PMID:33567294)
• Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. (PMID:33803916)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-76k16.5	ENSDARG00000075561
danio_rerio	si:dkey-76k16.6	ENSDARG00000077481
danio_rerio	si:ch73-106k19.2	ENSDARG00000102568
mus_musculus	Glyat	ENSMUSG00000063683
rattus_norvegicus	Glyat	ENSRNOG00000012142
caenorhabditis_elegans		WBGENE00011681
caenorhabditis_elegans		WBGENE00018400
caenorhabditis_elegans		WBGENE00022683

Paralogs (4): GLYATL2 (ENSG00000156689), GLYATL1 (ENSG00000166840), GLYATL3 (ENSG00000203972), GLYATL1B (ENSG00000255151)

Protein

Protein identifiers

Glycine N-acyltransferase — Q6IB77 (reviewed: Q6IB77)

Alternative names: Acyl-CoA:glycine N-acyltransferase, Aralkyl acyl-CoA N-acyltransferase, Aralkyl acyl-CoA:amino acid N-acyltransferase, Benzoyl-coenzyme A:glycine N-acyltransferase, Glycine N-benzoyltransferase, HRP-1(CLP)

All UniProt accessions (3): Q6IB77, A0A384P5E3, K7ES21

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently. Can conjugate numerous substrates to form a variety of N-acylglycines, with a preference for benzoyl-CoA over phenylacetyl-CoA as acyl donors. Thereby detoxify xenobiotics, such as benzoic acid or salicylic acid, and endogenous organic acids, such as isovaleric acid.

Subcellular location. Mitochondrion.

Tissue specificity. Predominantly expressed in liver (at protein level) and kidney. Down-regulated in hepatocellular carcinoma and other liver cancers.

Similarity. Belongs to the glycine N-acyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IB77-1	1	yes
Q6IB77-2	2

RefSeq proteins (2): NP_005829, NP_964011* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010313	Glycine_N-acyltransferase	Family
IPR013652	Glycine_N-acyltransferase_C	Domain
IPR015938	Glycine_N-acyltransferase_N	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily

Pfam: PF06021, PF08444

Enzyme classification (BRENDA):

• EC 2.3.1.13 — glycine N-acyltransferase (BRENDA: 7 organisms, 40 substrates, 29 inhibitors, 71 Km, 14 kcat entries)
• EC 2.3.1.71 — glycine N-benzoyltransferase (BRENDA: 4 organisms, 57 substrates, 27 inhibitors, 51 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

30 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BENZOYL-COA	0.0094–998	28
BENZOYL-COA	0.0094–998	24
GLYCINE	0.0016–79	19
GLYCINE	0.0016–79	12
BUTYRYL-COA	0.052–0.7	3
SALICYL-COA	0.03–83.7	3
GLY	6–6.4	3
ACETYL-COA	0.209	2
ALANINE	997–1573	2
HEXANOYL-COA	0.045–450	2
ISOVALERYL-COA	73.3–124	2
OCTANOYL-COA	108.6–198	2
ALA	997–1573	2
ASPARAGINE	129	1
GLUTAMIC ACID	1150	1

Catalyzed reactions (Rhea), 2 shown:

• benzoyl-CoA + glycine = N-benzoylglycine + CoA + H(+) (RHEA:18493)
• an acyl-CoA + glycine = an N-acylglycine + CoA + H(+) (RHEA:19869)

UniProt features (17 total): modified residue 12, splice variant 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IB77-F1	95.71	0.95

Functional residue map

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

Post-translational modifications (12): 16, 183, 256, 256, 16, 127, 127, 141, 141, 159, 169, 183

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-159424	Conjugation of carboxylic acids
R-HSA-177128	Conjugation of salicylate with glycine
R-HSA-177135	Conjugation of benzoate with glycine
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-9749641	Aspirin ADME

MSigDB gene sets: 124 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MODULE_64, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MODULE_75, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOBP_AMIDE_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_DN, GOBP_GLYCINE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, LEE_LIVER_CANCER_DENA_DN

GO Biological Process (6): glycine metabolic process (GO:0006544), acyl-CoA metabolic process (GO:0006637), xenobiotic metabolic process (GO:0006805), response to toxic substance (GO:0009636), monocarboxylic acid metabolic process (GO:0032787), benzoyl-CoA metabolic process (GO:1901787)

GO Molecular Function (6): acyltransferase activity (GO:0016746), glycine N-acyltransferase activity (GO:0047961), glycine N-benzoyltransferase activity (GO:0047962), protein binding (GO:0005515), obsolete N-acyltransferase activity (GO:0016410), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Conjugation of carboxylic acids	2
Amino Acid conjugation	1
Metabolism of amino acids and derivatives	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteinogenic amino acid metabolic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
response to chemical	1
carboxylic acid metabolic process	1
acyl-CoA metabolic process	1
transferase activity	1
amino acid acyltransferase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLYAT	BAAT	Q14032	882
GLYAT	GGCT	O75223	780
GLYAT	AGA	P20933	743
GLYAT	GUCY2C	P25092	673
GLYAT	ACSM2B	Q68CK6	643
GLYAT	DOCK11	Q5JSL3	613
GLYAT	GGTLC3	B5MD39	609
GLYAT	GGT1	P19440	585
GLYAT	TSHZ1	Q6ZSZ6	581
GLYAT	GLS	O94925	574
GLYAT	GGT2P	P36268	574
GLYAT	GCG	P01275	573
GLYAT	ACSM2A	Q08AH3	572
GLYAT	PROCR	Q9UNN8	527
GLYAT	VOPP1	Q96AW1	476

IntAct

11 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	GLYAT	psi-mi:“MI:0915”(physical association)	0.560
GLYAT	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
GLYAT	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	GLYAT	psi-mi:“MI:0915”(physical association)	0.560
GLYAT	PA	psi-mi:“MI:0915”(physical association)	0.370
GLYAT	RBM48	psi-mi:“MI:0915”(physical association)	0.000
GLYAT	VOPP1	psi-mi:“MI:0915”(physical association)	0.000
GLYAT	PTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), RBM48 (Two-hybrid), GPRASP1 (Two-hybrid), PTN (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), GLYAT (Two-hybrid), GLYAT (Two-hybrid), GLYAT (Two-hybrid), GLYAT (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0U1RQE8, F1S5L4, O43010, O77512, P06592, P13233, P14714, P42498, P49895, P55004, P97564, Q07071, Q09305, Q0P464, Q0P4Y1, Q1LYL8, Q2KHV5, Q2KIR7, Q3UW68, Q5BK10, Q5FW57, Q5GJ77, Q5PQT3, Q5RFP0, Q60462, Q61586, Q62240, Q64112, Q6IB77, Q6MZZ7, Q6P5U7, Q6QN13, Q6QR59, Q6V915, Q7L7V1, Q804E1, Q8CBA2, Q8T773, Q8WU03, Q91754

Diamond homologs: A0A0U1RQE8, E9Q5L8, O77512, Q2KIR7, Q5FW57, Q5PQT3, Q5RFP0, Q5SZD4, Q6IB77, Q8WU03, Q91XE0, Q969I3, Q9DCY0, Q9Z2Y0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

603 predictions. Top by Δscore:

Variant	Effect	Δscore
11:58712756:TTA:T	donor_loss	1.0000
11:58712757:TA:T	donor_loss	1.0000
11:58712758:A:AC	donor_gain	1.0000
11:58712758:ACTTT:A	donor_loss	1.0000
11:58712759:C:CG	donor_gain	1.0000
11:58712885:TC:T	acceptor_gain	1.0000
11:58712886:CCTGT:C	acceptor_gain	1.0000
11:58712887:C:CC	acceptor_gain	1.0000
11:58712894:CA:C	acceptor_gain	1.0000
11:58712895:A:C	acceptor_gain	1.0000
11:58712895:A:T	acceptor_gain	1.0000
11:58712896:T:C	acceptor_gain	1.0000
11:58712896:T:TC	acceptor_gain	1.0000
11:58715309:AACTT:A	donor_loss	1.0000
11:58715310:ACTT:A	donor_loss	1.0000
11:58715311:CTTA:C	donor_loss	1.0000
11:58715312:TTAC:T	donor_loss	1.0000
11:58715313:TACCT:T	donor_loss	1.0000
11:58715314:A:AC	donor_gain	1.0000
11:58715315:C:CC	donor_gain	1.0000
11:58715315:C:CG	donor_loss	1.0000
11:58715315:CCTG:C	donor_gain	1.0000
11:58715435:C:T	acceptor_gain	1.0000
11:58710182:A:T	acceptor_gain	0.9900
11:58712754:A:AC	donor_gain	0.9900
11:58712755:C:CC	donor_gain	0.9900
11:58712755:CTTA:C	donor_gain	0.9900
11:58712759:CT:C	donor_gain	0.9900
11:58712883:TATC:T	acceptor_gain	0.9900
11:58712885:TCCT:T	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000030467 (11:58718282 C>A), RS1000098982 (11:58724603 T>G), RS1000113181 (11:58730202 T>A,C), RS1000186089 (11:58726021 C>T), RS1000229688 (11:58729936 T>C), RS1000269073 (11:58718409 A>G), RS1000528693 (11:58730120 T>C), RS1000551388 (11:58722845 C>A,T), RS1000565438 (11:58728854 G>A), RS1000916051 (11:58708908 T>C), RS1001158942 (11:58718063 A>C,T), RS1001450260 (11:58729532 C>T), RS1001484232 (11:58713365 T>C), RS1001560265 (11:58729310 C>T), RS1001790169 (11:58723805 T>A)

Disease associations

OMIM: gene MIM:607424 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001722_1	Body mass (lean)	2.000000e-08
GCST003944_41	Hepcidin/ferritin ratio	9.000000e-06
GCST004133_47	Ulcerative colitis	9.000000e-06
GCST005537_72	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-08
GCST007094_73	Diastolic blood pressure	3.000000e-06
GCST007096_85	Pulse pressure	1.000000e-12
GCST007099_73	Systolic blood pressure	1.000000e-13
GCST012489_110	Heel bone mineral density x serum urate levels interaction	2.000000e-08
GCST90002393_228	Monocyte count	3.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004995	lean body mass
EFO:0007901	hepcidin:ferritin ratio
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Estradiol	affects expression, decreases expression, affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	decreases methylation, affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
methyleugenol	decreases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
Asbestos	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Endosulfan	affects cotreatment, decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	affects cotreatment, decreases expression	1
Glycodeoxycholic Acid	affects cotreatment, decreases expression	1
Progesterone	increases expression, affects cotreatment	1
Pyrrolizidine Alkaloids	decreases expression	1
Silicon Dioxide	decreases expression	1
Tamoxifen	affects expression	1
Testosterone	increases expression	1
Triclosan	affects cotreatment, decreases expression	1
Okadaic Acid	decreases expression	1
Raloxifene Hydrochloride	affects expression	1
Nanotubes, Carbon	decreases expression	1

Clinical trials (associated diseases)

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