GPAM

Summary

GPAM (glycerol-3-phosphate acyltransferase, mitochondrial, HGNC:24865) is a protein-coding gene on chromosome 10q25.2, encoding Glycerol-3-phosphate acyltransferase 1, mitochondrial (Q9HCL2). Mitochondrial membrane protein that catalyzes the essential first step of biosynthesis of glycerolipids such as triglycerides, phosphatidic acids and lysophosphatidic acids.

This gene encodes a mitochondrial enzyme which prefers saturated fatty acids as its substrate for the synthesis of glycerolipids. This metabolic pathway’s first step is catalyzed by the encoded enzyme. Two forms for this enzyme exist, one in the mitochondria and one in the endoplasmic reticulum. Two alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 57678 — RefSeq curated summary.

At a glance

• GWAS associations: 66 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 115 total — 1 pathogenic
• GTEx eGene: eQTL in 23 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.75 (unconstrained)
• MANE Select transcript: NM_001244949
• Notable: 115 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24865
Approved symbol	GPAM
Name	glycerol-3-phosphate acyltransferase, mitochondrial
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1560, MGC26846, GPAT1
Ensembl gene	ENSG00000119927
Ensembl biotype	protein_coding
OMIM	602395
Entrez	57678

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000348367

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1

ENST00000348367, ENST00000369425, ENST00000480130, ENST00000498541, ENST00000901835, ENST00000901836, ENST00000901837, ENST00000901838, ENST00000901839, ENST00000901840, ENST00000901841, ENST00000901842, ENST00000901843, ENST00000901844, ENST00000964625, ENST00001015590, ENST00001015591, ENST00001015593, ENST00001015594, ENST00001015595, ENST00001063031, ENST00001063032, ENST00001107556

RefSeq mRNA: 2 — MANE Select: NM_001244949 NM_001244949, NM_020918

CCDS: CCDS7570

Canonical transcript exons

ENST00000348367 — 22 exons

Exon	Start	End
ENSE00000811856	112154629	112154687
ENSE00000811857	112155864	112156053
ENSE00000811858	112157249	112157389
ENSE00000811859	112158316	112158393
ENSE00000811860	112159911	112160053
ENSE00000811861	112160604	112160868
ENSE00000811862	112161667	112161737
ENSE00000811863	112163701	112163816
ENSE00000811864	112164525	112164610
ENSE00000811865	112166402	112166515
ENSE00000811866	112168312	112168524
ENSE00000811867	112168853	112168952
ENSE00000811868	112172182	112172318
ENSE00000811870	112173699	112173845
ENSE00000811871	112175600	112175713
ENSE00000811872	112177984	112178057
ENSE00000811873	112180473	112180595
ENSE00001353079	112182794	112182891
ENSE00001353090	112183693	112183765
ENSE00001363922	112172970	112173066
ENSE00001944831	112149865	112153666
ENSE00003615463	112181683	112181813

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6950 / max 843.0406, expressed in 1619 samples.

Highest expression (Bgee): pericardium, corpus epididymis, skin of hip, liver, adipose tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GPAM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	8.9e-34	-0.56	10:112175621:T:C
Cells Cultured fibroblasts	eqtl	9.2e-20	-0.35	10:112227082:G:A
Brain Cerebellar Hemisphere	eqtl	8.9e-12	+0.43	10:112169741:C:G
Artery Tibial	eqtl	4.1e-07	-0.19	10:112168729:A:C
Esophagus Gastroesophageal Junction	eqtl	9.2e-06	-0.24	10:112184513:A:G
Breast Mammary Tissue	eqtl	5.3e-05	-0.15	10:112242269:C:T
Brain Caudate basal ganglia	eqtl	9.7e-05	+0.13	10:112166657:T:C
Cells Cultured fibroblasts	sqtl	7.0e-04	-0.28	10:112181071:A:G
Adipose Visceral Omentum	eqtl	1.2e-03	-0.12	10:112228257:C:A
Muscle Skeletal	eqtl	1.4e-03	-0.18	10:112153239:A:C
Artery Aorta	eqtl	1.4e-03	+0.26	10:112159840:C:T
Adipose Subcutaneous	eqtl	1.9e-03	-0.11	10:112285575:C:T
Brain Cortex	eqtl	2.2e-03	+0.11	10:112148302:T:C
Brain Hypothalamus	eqtl	4.4e-03	+0.18	10:112178528:C:T
Spleen	eqtl	6.1e-03	+0.30	10:112294843:A:G
Brain Anterior cingulate cortex BA24	eqtl	9.5e-03	-0.99	10:111216342:G:T
Brain Nucleus accumbens basal ganglia	eqtl	1.3e-02	+0.33	10:112394593:G:C
Brain Cerebellum	eqtl	1.4e-02	-2.03	10:112409387:G:T
Ovary	eqtl	1.8e-02	-0.24	10:112168729:A:C
Brain Amygdala	eqtl	3.2e-02	-0.24	10:112225671:T:A

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
111418	6.8519	1607
111423	6.0063	144
111415	0.3122	117
111424	0.2009	49
111422	0.1317	41
111416	0.0628	33
111414	0.0388	18
111413	0.0269	13
111417	0.0233	7
111420	0.0154	8

Top tissues by expression

showing 100 of 255 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.23	gold quality
corpus epididymis	UBERON:0004359	98.98	gold quality
skin of hip	UBERON:0001554	96.96	gold quality
liver	UBERON:0002107	96.20	gold quality
adipose tissue	UBERON:0001013	95.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.66	gold quality
vena cava	UBERON:0004087	95.40	gold quality
synovial joint	UBERON:0002217	95.13	gold quality
right adrenal gland cortex	UBERON:0035827	95.06	gold quality
right lobe of liver	UBERON:0001114	94.91	gold quality
mammary duct	UBERON:0001765	94.52	gold quality
right adrenal gland	UBERON:0001233	94.34	gold quality
epithelium of mammary gland	UBERON:0003244	94.21	gold quality
thoracic mammary gland	UBERON:0005200	93.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.84	gold quality
adrenal cortex	UBERON:0001235	93.77	gold quality
mammary gland	UBERON:0001911	93.73	gold quality
omental fat pad	UBERON:0010414	93.52	gold quality
peritoneum	UBERON:0002358	93.49	gold quality
left adrenal gland	UBERON:0001234	93.44	gold quality
adrenal gland	UBERON:0002369	93.18	gold quality
left adrenal gland cortex	UBERON:0035825	93.00	gold quality
adrenal tissue	UBERON:0018303	92.98	gold quality
lateral globus pallidus	UBERON:0002476	92.24	gold quality
globus pallidus	UBERON:0001875	91.19	gold quality
medial globus pallidus	UBERON:0002477	90.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.40	gold quality
cauda epididymis	UBERON:0004360	90.11	gold quality
pigmented layer of retina	UBERON:0001782	89.46	gold quality
caput epididymis	UBERON:0004358	89.34	gold quality
pancreatic ductal cell	CL:0002079	88.98	gold quality
layer of synovial tissue	UBERON:0007616	88.40	gold quality
secondary oocyte	CL:0000655	88.05	gold quality
endothelial cell	CL:0000115	87.72	gold quality
parietal pleura	UBERON:0002400	87.70	gold quality
deltoid	UBERON:0001476	87.12	gold quality
cortical plate	UBERON:0005343	86.37	gold quality
biceps brachii	UBERON:0001507	86.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.81	gold quality
nucleus accumbens	UBERON:0001882	85.58	gold quality
ventricular zone	UBERON:0003053	85.49	gold quality
skeletal muscle tissue	UBERON:0001134	85.37	gold quality
putamen	UBERON:0001874	84.59	gold quality
caudate nucleus	UBERON:0001873	84.43	gold quality
muscle tissue	UBERON:0002385	84.27	gold quality
amygdala	UBERON:0001876	83.82	gold quality
substantia nigra pars compacta	UBERON:0001965	83.68	gold quality
superficial temporal artery	UBERON:0001614	83.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.56	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.24	gold quality
temporal lobe	UBERON:0001871	83.23	gold quality
vastus lateralis	UBERON:0001379	83.16	gold quality
calcaneal tendon	UBERON:0003701	83.11	gold quality
ventral tegmental area	UBERON:0002691	82.91	gold quality
entorhinal cortex	UBERON:0002728	82.87	gold quality
quadriceps femoris	UBERON:0001377	82.77	silver quality
tibialis anterior	UBERON:0001385	82.58	gold quality
ganglionic eminence	UBERON:0004023	82.53	gold quality
coronary artery	UBERON:0001621	82.10	gold quality
superior vestibular nucleus	UBERON:0007227	82.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.09	gold quality
dorsal plus ventral thalamus	UBERON:0001897	82.04	gold quality
left coronary artery	UBERON:0001626	81.95	gold quality
occipital lobe	UBERON:0002021	81.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.90	gold quality
jejunum	UBERON:0002115	81.55	gold quality
medulla oblongata	UBERON:0001896	81.48	gold quality
primary visual cortex	UBERON:0002436	81.23	gold quality
lateral nuclear group of thalamus	UBERON:0002736	81.00	gold quality
subthalamic nucleus	UBERON:0001906	80.92	gold quality
trachea	UBERON:0003126	80.58	gold quality
inferior vagus X ganglion	UBERON:0005363	80.45	gold quality
right lobe of thyroid gland	UBERON:0001119	80.36	gold quality
corpus callosum	UBERON:0002336	80.11	gold quality
midbrain	UBERON:0001891	79.62	gold quality
body of tongue	UBERON:0011876	79.62	gold quality
gall bladder	UBERON:0002110	79.41	gold quality
substantia nigra	UBERON:0002038	79.40	gold quality
jejunal mucosa	UBERON:0000399	79.20	gold quality
muscle of leg	UBERON:0001383	79.16	gold quality
upper arm skin	UBERON:0004263	79.05	silver quality
saphenous vein	UBERON:0007318	78.87	gold quality
parietal lobe	UBERON:0001872	78.71	gold quality
heart	UBERON:0000948	78.66	gold quality
gastrocnemius	UBERON:0001388	78.63	gold quality
postcentral gyrus	UBERON:0002581	78.43	gold quality
tibia	UBERON:0000979	78.30	gold quality
forebrain	UBERON:0001890	78.25	gold quality
cardiac atrium	UBERON:0002081	78.20	gold quality
Ammon’s horn	UBERON:0001954	78.01	gold quality
left lobe of thyroid gland	UBERON:0001120	77.98	gold quality
heart left ventricle	UBERON:0002084	77.83	gold quality
left ventricle myocardium	UBERON:0006566	77.77	gold quality
tibial nerve	UBERON:0001323	77.75	gold quality
brain	UBERON:0000955	77.66	gold quality
thyroid gland	UBERON:0002046	77.66	gold quality
right atrium auricular region	UBERON:0006631	77.59	gold quality
cardiac ventricle	UBERON:0002082	77.53	gold quality
right frontal lobe	UBERON:0002810	77.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	54.52
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Adipose tissue	tissue	287.2	medium
Liver	tissue	134.8	low
Epididymis	tissue	70.9	not detected
Thalamus	tissue	57.0
Caudate putamen	tissue	53.0
Midbrain	tissue	51.6
Pons	tissue	49.6
Periaqueductal gray	tissue	48.1
Superior colliculi	tissue	45.9
Medulla oblongata	tissue	45.6
Amygdala	tissue	43.3
Putamen	tissue	43.1
Substantia nigra	tissue	42.8
Spinal cord	tissue	42.7
Frontal cortex	tissue	41.7
Hypothalamus	tissue	40.9
Cerebral cortex	tissue	40.7	not detected
Motor cortex	tissue	40.7
Occipital cortex	tissue	40.3
Hippocampal formation	tissue	39.7
Entorhinal cortex	tissue	39.7
Temporal cortex	tissue	39.4
Insular cortex	tissue	38.7
Somatosensory cortex	tissue	38.6
Prefrontal cortex	tissue	38.0
Ventral forebrain	tissue	37.3
Retrosplenial cortex	tissue	34.9
Retrosplenial and cingulate cortex	tissue	34.7
Septum	tissue	33.5
Adrenal gland	tissue	31.3	low
Olfactory bulb	tissue	28.4
Basal ganglia	tissue	28.0	not detected
Nucleus accumbens	tissue	21.7
Breast	tissue	17.8	medium
Salivary gland	tissue	16.2	not detected
Locus coeruleus	tissue	15.6
Hippocampus	tissue	15.6	not detected
Cerebellum	tissue	15.3	not detected
Postcentral gyrus	tissue	15.2
Corpus callosum	tissue	12.0
Thyroid gland	tissue	11.6	not detected
Heart muscle	tissue	11.5	not detected
Tongue	tissue	8.2
Skeletal muscle	tissue	7.8	not detected
Colon	tissue	6.0	not detected
Gallbladder	tissue	5.6	not detected
Testis	tissue	5.3	high
Seminal vesicle	tissue	5.0	not detected
Choroid plexus	tissue	5.0
Retina	tissue	4.7
Pancreas	tissue	4.7	not detected
Smooth muscle	tissue	4.6	not detected
Ovary	tissue	4.5	not detected
Appendix	tissue	4.5	not detected
Rectum	tissue	4.4	not detected
Lymph node	tissue	4.3	not detected
Kidney	tissue	4.1	not detected
Parathyroid gland	tissue	4.0	not detected
Tonsil	tissue	4.0	not detected
Endometrium 1	tissue	3.9	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Ventral spinal cord (42.7), Subiculum (35.3), Ventral hippocampus (31.5), Dorsal hippocampus (28.5), Dorsal spinal cord (27.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, FOXO1, HNF4A, NFYA, PPARD, PPARG, SREBF1, USF1

miRNA regulators (miRDB)

Targeting GPAM by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 158 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-338-5P	99.92	72.34	2951

Functional genomics

gnomAD constraint: pLI 0.000785, LOEUF 0.747, missense Z 1.38 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000348367 — one region, missense o/e 0.86.

Literature-anchored findings (GeneRIF, showing 7)

• Results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes. (PMID:22070544)
• two transcriptional initiation sites and two promoters (promoter I and II) required for expression of the human GPAT1 (hGPAT1) gene were identified. (PMID:22634312)
• High GPAM expression is associated with Ovarian Carcinoma. (PMID:28652252)
• Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease. (PMID:33347879)
• Genetic Variation in the Mitochondrial Glycerol-3-Phosphate Acyltransferase Is Associated With Liver Injury. (PMID:34216018)
• [Identification of GPAT1-dependent mitochondrial metabolism as a novel therapeutic target for AML]. (PMID:35662157)
• Structural basis of the acyl-transfer mechanism of human GPAT1. (PMID:36522428)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpam	ENSDARG00000074169
mus_musculus	Gpam	ENSMUSG00000024978
rattus_norvegicus	Gpam	ENSRNOG00000015124
drosophila_melanogaster	mino	FBGN0027579
caenorhabditis_elegans		WBGENE00017261

Paralogs (2): GNPAT (ENSG00000116906), GPAT2 (ENSG00000186281)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109162) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased percent body fat/body weight	3
decreased circulating triglyceride level	2
decreased circulating cholesterol level	2
slow postnatal weight gain	2
decreased gonadal fat pad weight	2
decreased liver triglyceride level	2
decreased circulating HDL cholesterol level	1
abnormal hepatocyte morphology	1
abnormal liver physiology	1
decreased body weight	1
abnormal lipid homeostasis	1
increased circulating ketone body level	1
decreased circulating insulin level	1
decreased circulating VLDL triglyceride level	1
abnormal fatty acids level	1
insulin resistance	1
decreased retroperitoneal fat pad weight	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	F1S5L4	96.0%	Diamond
Bos taurus	Q5GJ77	95.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6715A	ncRNA	102466189
ACSL5	protein-coding	51703
ZDHHC6	protein-coding	64429
TECTB	protein-coding	6975
MIR6715B	ncRNA	102465427
MIR4295	ncRNA	100422909
VTI1A	protein-coding	143187

Protein

Protein identifiers

Glycerol-3-phosphate acyltransferase 1, mitochondrial — Q9HCL2 (reviewed: Q9HCL2)

All UniProt accessions (2): Q5VW52, Q9HCL2

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial membrane protein that catalyzes the essential first step of biosynthesis of glycerolipids such as triglycerides, phosphatidic acids and lysophosphatidic acids. Esterifies acyl-group from acyl-coenzyme A (acyl-CoA) to the sn-1 position of glycerol-3-phosphate, to produce lysophosphatidic acid. Has a narrow hydrophobic binding cleft that selects for a linear acyl chain. Catalytic activity is higher for substrates with a 16-carbon acyl chain.

Subcellular location. Mitochondrion outer membrane.

Domain organisation. The HXXXXD motif is essential for acyltransferase activity and contributes to the binding of the cysteamine moiety of the acyl-CoA and the phosphate moiety of the glycerol-3-phosphate.

Pathway. Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-diacylglycerol from sn-glycerol 3-phosphate: step 1/3.

Similarity. Belongs to the GPAT/DAPAT family.

RefSeq proteins (2): NP_001231878, NP_065969 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002123	Plipid/glycerol_acylTrfase	Domain
IPR022284	GPAT/DHAPAT	Family
IPR028354	GPAT_PlsB	Family
IPR041728	GPAT/DHAPAT_LPLAT	Domain
IPR045520	GPAT/DHAPAT_C	Domain

Pfam: PF01553, PF19277

Enzyme classification (BRENDA)

• EC 2.3.1.15 — glycerol-3-phosphate 1-O-acyltransferase (BRENDA: 53 organisms, 165 substrates, 174 inhibitors, 109 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
SN-GLYCEROL 3-PHOSPHATE	0.021–4.2	29
PALMITOYL-COA	0.002–1.5	20
GLYCEROL 3-PHOSPHATE	0.025–16.4	14
OLEOYL-COA	0.005–0.1	12
STEAROYL-COA	0.004–0.013	4
MYRISTOYL-COA	0.012–0.016	3
PALMITOYL-[ACYL CARRIER PROTEIN]	0.0034–0.015	3
OLEOYL-ACP	0.0028–0.003	2
PALMITOYL-ACP	0.0032–0.0056	2
ACYL-ACP	0.07	1
OLEOYL-[ACYL-CARRIER PROTEIN]	0.0078	1
PALMITOLEOYL-COA	0.0267	1
PALMITOYL-[ACYL-CARRIER PROTEIN]	0.002	1
STEAROYL-ACP	0.0033	1
STEAROYL-[ACYL-CARRIER PROTEIN]	0.0061	1

Catalyzed reactions (Rhea)

• sn-glycerol 3-phosphate + an acyl-CoA = a 1-acyl-sn-glycero-3-phosphate + CoA (RHEA:15325)
• 1-acyl-sn-glycero-3-phospho-(1’-sn-glycerol) + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol) + CoA (RHEA:33203)
• sn-glycerol 3-phosphate + hexadecanoyl-CoA = 1-hexadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:35723)
• dodecanoyl-CoA + sn-glycerol 3-phosphate = 1-dodecanoyl-sn-glycerol 3-phosphate + CoA (RHEA:35727)
• sn-glycerol 3-phosphate + octadecanoyl-CoA = 1-octadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37195)
• sn-glycerol 3-phosphate + (9Z)-octadecenoyl-CoA = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37199)
• (9Z,12Z)-octadecadienoyl-CoA + sn-glycerol 3-phosphate = 1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + CoA (RHEA:37203)

UniProt features (98 total): helix 36, strand 19, mutagenesis site 15, binding site 6, modified residue 5, sequence variant 4, turn 3, topological domain 2, sequence conflict 2, region of interest 2, chain 1, intramembrane region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8E4Y	Cryo-EM structure of human glycerol-3-phosphate acyltransferase 1 (GPAT1) in complex with …	ELECTRON MICROSCOPY	3.4
8E50	Cryo-EM structure of human glycerol-3-phosphate acyltransferase 1 (GPAT1) in complex with …	ELECTRON MICROSCOPY	3.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCL2-F1	80.32	0.49

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
288	CoA
293	CoA
328	CoA
462	CoA
278	CoA
279	CoA

Post-translational modifications (5)

Type	Positions
Phosphoserine	380, 688, 695
N6-acetyllysine	780, 784

Mutagenesis-validated functional residues (15)

Position	Phenotype
89	abrogates mitochondrial localization; when associated with e-98, e-100, e-101, e-102, e-107, e-108 and e-118.
98	abrogates mitochondrial localization; when associated with e-89, e-100, e-101, e-102, e-107, e-108 and e-118.
100	abrogates mitochondrial localization; when associated with e-89, e-98, e-101, e-102, e-107, e-108 and e-118.
101	abrogates mitochondrial localization; when associated with e-89, e-98, e-100, e-102, e-107, e-108 and e-118.
102	abrogates mitochondrial localization; when associated with e-89, e-98, e-100, e-101, e-107, e-108 and e-118.
107	abrogates mitochondrial localization; when associated with e-89, e-98, e-100, e-101, e-102, e-108 and e-118.
108	abrogates mitochondrial localization; when associated with e-89, e-98, e-100, e-101, e-102, e-107 and e-118.
118	abrogates mitochondrial localization; when associated with e-89, e-98, e-100, e-101, e-102, e-107 and e-108.
230	abolishes catalytic activity.
233	abolishes catalytic activity.
273	abolishes catalytic activity.
278	abolishes catalytic activity.
313	abolishes catalytic activity.
318	abolishes catalytic activity.
388	impairs catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 24; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

24 pathways:

ID	Pathway	Evidence
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)	curated
R-HSA-9018519	Estrogen-dependent gene expression	curated
R-HSA-8931987	RUNX1 regulates estrogen receptor mediated transcription	curated
R-HSA-1483166	Synthesis of PA	curated
R-HSA-75109	Triglyceride biosynthesis	curated
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes	—
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-1483206	Glycerophospholipid biosynthesis	—
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	electronic
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-8957322	Metabolism of steroids	—
R-HSA-1483257	Phospholipid metabolism	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006931	Signaling by Nuclear Receptors	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—
R-HSA-8979227	Triglyceride metabolism	—

MSigDB gene sets: 322 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_T_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (8): glycerophospholipid metabolic process (GO:0006650), diacylglycerol biosynthetic process (GO:0006651), phosphatidic acid biosynthetic process (GO:0006654), phosphatidylglycerol biosynthetic process (GO:0006655), CDP-diacylglycerol biosynthetic process (GO:0016024), triglyceride biosynthetic process (GO:0019432), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (4): glycerol-3-phosphate O-acyltransferase activity (GO:0004366), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), plasma membrane (GO:0005886), mitochondrial membrane (GO:0031966)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Metabolism of lipids	3
Gene expression (Transcription)	2
Glycerophospholipid biosynthesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Triglyceride metabolism	1
Transcriptional regulation by RUNX1	1
ESR-mediated signaling	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Phospholipid metabolism	1
Metabolism of steroids	1
RNA Polymerase II Transcription	1
Metabolism	1
Generic Transcription Pathway	1
Signaling by Nuclear Receptors	1

GO top-level categories

25 GO namespaces:

Category	Terms
glycerophospholipid biosynthetic process	3
phospholipid metabolic process	2
acylglycerol biosynthetic process	2
glycerolipid metabolic process	1
diacylglycerol metabolic process	1
phosphatidic acid metabolic process	1
phosphatidylglycerol metabolic process	1
CDP-diacylglycerol metabolic process	1
triglyceride metabolic process	1
primary metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
catalytic activity	1
transferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
phosphatidylglycerol biosynthetic process	BP	mutant phenotype
triglyceride biosynthetic process	BP	direct assay
mitochondrion	CC	high-throughput
glycerol-3-phosphate O-acyltransferase activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,068 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPAM	GPAT3	Q53EU6	937
GPAM	LPGAT1	Q92604	887
GPAM	GPAT4	Q86UL3	886
GPAM	SCD5	Q86SK9	838
GPAM	SCD	O00767	817
GPAM	AGPAT2	O15120	741
GPAM	FASN	P49327	741
GPAM	AGPAT1	Q99943	741
GPAM	DGAT1	O75907	730
GPAM	DGAT2	Q96PD7	717
GPAM	PCK1	P35558	695
GPAM	ACACA	Q13085	687
GPAM	SREBF1	P36956	662
GPAM	AGPAT3	Q9NRZ7	658
GPAM	LPIN1	Q14693	649

IntAct

Human interaction partners of GPAM in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
CIDEB	physical association	0.560	3
COQ9	association	0.500	2
HNRNPC	physical association	0.400	1
ALDH1L1	association	0.350	2
SRC	association	0.350	1

BioGRID (39 interactions; top human partners by supporting records): SIRT2 (Affinity Capture-MS; 3 records), APP (Reconstituted Complex; 2 records), ATP2B2 (Affinity Capture-MS; 2 records), CDH5 (Affinity Capture-MS; 2 records), PSMC4 (Affinity Capture-MS; 2 records), AKAP1 (Proximity Label-MS), CADM4 (Affinity Capture-MS), CIDEB (Two-hybrid), CLU (Affinity Capture-MS), ECH1 (Affinity Capture-MS), FBXO7 (Biochemical Activity), FIS1 (Proximity Label-MS), HDAC1 (Affinity Capture-MS), IDE (Affinity Capture-MS), KIAA1429 (Affinity Capture-RNA)

Disease & clinical

Genetic variants

Variant evidence for GPAM: 115 ClinVar records (1 pathogenic / likely pathogenic); 66 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	93
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4083503	GRCh37/hg19 10q25.2-25.3(chr10:113914387-115668295)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GPAM’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 1,718):

Position(s)	Effect	Δscore	Sites
10:112155858	donor_gain	1.0000
10:112158314–112158315	donor_loss	1.0000	5
10:112159909–112159910	donor_loss	1.0000	4
10:112160054–112160055	acceptor_loss	1.0000	6
10:112160869–112160870	acceptor_loss	1.0000	4
10:112161665–112161666	donor_loss	1.0000	4
10:112163699–112163700	donor_loss	1.0000	5
10:112163818	acceptor_loss	1.0000	3
10:112164523–112164524	donor_loss	1.0000	4
10:112164611–112164612	acceptor_loss	1.0000	6

AlphaMissense

1,989 missense substitutions predicted likely pathogenic (of 5,445 scored), across 512 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M483	9	0.950	0.999
M177	9	0.883	0.987
D235	8	0.998	0.999
H230	8	0.986	0.998
D522	8	0.985	0.992
D289	8	0.978	0.994
H233	8	0.975	0.994
F525	8	0.969	0.999
H471	8	0.967	0.989
D399	8	0.948	0.980
F809	8	0.947	0.993
D696	8	0.932	0.980
F201	8	0.931	0.981
H207	8	0.928	0.989
F62	8	0.924	0.990
F567	8	0.923	0.986
D694	8	0.921	0.983
N258	8	0.918	0.993
F226	8	0.910	0.996
F400	8	0.907	0.996

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.68e-05

Disease associations

OMIM: gene MIM:602395 | disease phenotypes:

GWAS associations

showing 30 of 66 associations:

Study	Trait	p-value
GCST010241_162	Apolipoprotein A1 levels	2e-65
GCST010242_81	HDL cholesterol levels	3e-64
GCST90013406_233	Liver enzyme levels (alkaline phosphatase)	2e-49
GCST90013405_133	Liver enzyme levels (alanine transaminase)	3e-39
GCST90011900_123	Serum alkaline phosphatase levels	6e-35
GCST90013663_41	Alanine aminotransferase levels	3e-33
GCST008084_165	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-32
GCST90011898_15	Alanine aminotransferase levels	1e-30
GCST010241_82	Apolipoprotein A1 levels	3e-29
GCST010242_515	HDL cholesterol levels	8e-29
GCST008075_170	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3e-27
GCST006611_41	HDL cholesterol	6e-21
GCST008085_183	HDL cholesterol levels in current drinkers	2e-19
GCST010204_187	Low density lipoprotein cholesterol levels	6e-19
GCST004235_36	Total cholesterol levels	2e-18
GCST006612_100	LDL cholesterol	2e-18
GCST008084_63	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-18
GCST008070_69	HDL cholesterol levels	1e-16
GCST011348_53	High density lipoprotein cholesterol levels	1e-16
GCST010244_150	Triglyceride levels	2e-16
GCST002221_52	Cholesterol, total	7e-16
GCST004233_62	LDL cholesterol levels	1e-15
GCST008075_94	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-15
GCST010245_223	LDL cholesterol levels	6e-15
GCST011346_62	Total cholesterol levels	1e-14
GCST008079_132	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7e-14
GCST002222_44	LDL cholesterol	1e-13
GCST010244_346	Triglyceride levels	1e-13
GCST90016673_4	Percent liver fat	4e-13
GCST008078_88	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7e-13

EFO canonical traits (from GWAS)

12 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking
EFO:0004995	lean body mass
EFO:0005059	acylcarnitine measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007985	platelet crit
EFO:0004736	aspartate aminotransferase measurement
EFO:0010821	liver fat measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3734642 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3736092	IC50	760 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression, decreases reaction	4
Benzo(a)pyrene	affects cotreatment, decreases expression, increases methylation	4
Cyclosporine	affects expression, decreases expression	4
Acetaminophen	decreases expression	3
Valproic Acid	affects expression, affects methylation, decreases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Dexamethasone	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Oleic Acid	affects cotreatment, decreases reaction, increases expression	2
Palmitic Acid	decreases reaction, increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
cinnabarinic acid	decreases reaction, increases expression	1
OTX015	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
perfluoropentanoic acid	increases expression	1
mivebresib	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
fluorotelomer sulfonic acids	increases expression	1
perfluorotridecanoic acid	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
benzo(b)fluoranthene	affects cotreatment, decreases expression	1
acadesine	decreases reaction, increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
benz(a)anthracene	affects cotreatment, decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3737418	Binding	Inhibition of GPAT1 (unknown origin) by CPM assay using glycerol-3-phosphate and oleoyl-CoA as substrate	Discovery and Pharmacology of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7IT	SYSUe008-A	Embryonic stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.