GPAT2

Summary

GPAT2 (glycerol-3-phosphate acyltransferase 2, mitochondrial, HGNC:27168) is a protein-coding gene on chromosome 2q11.2, encoding Glycerol-3-phosphate acyltransferase 2, mitochondrial (Q6NUI2). Transfers an acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate producing a lysophosphatidic acid (LPA), an essential step for the triacylglycerol (TAG) and glycerophospholipids. It is a selective cancer dependency (DepMap: 32.1% of cell lines).

Enables glycerol-3-phosphate O-acyltransferase activity. Predicted to be involved in glycerol-3-phosphate metabolic process; glycerolipid biosynthetic process; and piRNA processing. Located in mitochondrion.

Source: NCBI Gene 150763 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 131 total — 3 likely-pathogenic
• Regional missense constraint (gnomAD): 4 of 7 regions constrained (≈20% of expected missense variation)
• GTEx eGene: eQTL in 36 tissues, sQTL in 10 (q < 0.05)
• Cancer dependency (DepMap): dependent in 32.1% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_001321527
• Notable: 131 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27168
Approved symbol	GPAT2
Name	glycerol-3-phosphate acyltransferase 2, mitochondrial
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	CT123
Ensembl gene	ENSG00000186281
Ensembl biotype	protein_coding
OMIM	616431
Entrez	150763

Gene structure

Transcript identifiers

Ensembl transcripts: 78 — 70 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000434632

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1, TSL 4: 2, TSL 5: 2

ENST00000434632, ENST00000359548, ENST00000439254, ENST00000453542, ENST00000468438, ENST00000471757, ENST00000482704, ENST00000484440, ENST00000486463, ENST00000488515, ENST00000687910, ENST00000862208, ENST00000862209, ENST00000862210, ENST00000862211, ENST00000862212, ENST00000862213, ENST00000862214, ENST00000862215, ENST00000862216, ENST00000862217, ENST00000862218, ENST00000964151, ENST00000964152, ENST00000964153, ENST00000964154, ENST00000964155, ENST00000964156, ENST00000964157, ENST00000964158, ENST00000964159, ENST00000964160, ENST00000964161, ENST00000964162, ENST00000964163, ENST00000964164, ENST00000964165, ENST00000964166, ENST00001001069, ENST00001001070, ENST00001044113, ENST00001044114, ENST00001044115, ENST00001044116, ENST00001044117, ENST00001044118, ENST00001044119, ENST00001044120, ENST00001044121, ENST00001044122, ENST00001044123, ENST00001044124, ENST00001101439, ENST00001101440, ENST00001101441, ENST00001101442, ENST00001101443, ENST00001101444, ENST00001101445, ENST00001101446, ENST00001101447, ENST00001101449, ENST00001101451, ENST00001101452, ENST00001101453, ENST00001101454, ENST00001101455, ENST00001101456, ENST00001101457, ENST00001101458, ENST00001101459, ENST00001101460, ENST00001101461, ENST00001101462, ENST00001101463, ENST00001101464, ENST00001101465, ENST00001138835

RefSeq mRNA: 8 — MANE Select: NM_001321527 NM_001321525, NM_001321526, NM_001321527, NM_001321528, NM_001321529, NM_001321530, NM_001321531, NM_001389639

CCDS: CCDS42714, CCDS82482, CCDS92810, CCDS92811

Canonical transcript exons

ENST00000434632 — 22 exons

Exon	Start	End
ENSE00001791718	96034853	96034916
ENSE00003460912	96026183	96026305
ENSE00003465984	96027007	96027106
ENSE00003466407	96032297	96032419
ENSE00003475496	96021946	96022275
ENSE00003476053	96031261	96031334
ENSE00003486994	96022958	96023023
ENSE00003520678	96032033	96032146
ENSE00003523199	96024773	96024843
ENSE00003544981	96022668	96022723
ENSE00003552049	96024189	96024337
ENSE00003555970	96025930	96026012
ENSE00003579999	96023106	96023226
ENSE00003580231	96025485	96025603
ENSE00003598552	96026697	96026909
ENSE00003630845	96030744	96030848
ENSE00003654860	96023923	96024000
ENSE00003655206	96030406	96030534
ENSE00003661697	96023309	96023440
ENSE00003926153	96024427	96024685
ENSE00003988991	96027991	96028090
ENSE00003988994	96027419	96027552

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 90.30.

Highest expression (Bgee): apex of heart, testis, heart left ventricle, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GPAT2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 36 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 46 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.2e-33	+0.52	2:95834541:T:C
Esophagus Muscularis	eqtl	3.3e-17	-1.06	2:95815543:C:T
Adipose Visceral Omentum	eqtl	2.2e-16	-0.97	2:96082306:A:G
Esophagus Gastroesophageal Junction	eqtl	9.1e-14	-1.04	2:96082306:A:G
Heart Left Ventricle	eqtl	2.0e-13	+0.41	2:95834541:T:C
Adipose Subcutaneous	eqtl	1.2e-12	-1.00	2:96082306:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.5e-12	-0.96	2:96230552:G:A
Heart Atrial Appendage	eqtl	1.6e-12	-1.00	2:96082306:A:G
Artery Tibial	eqtl	3.9e-12	-0.89	2:96082306:A:G
Skin Sun Exposed Lower leg	eqtl	7.0e-12	-0.75	2:96082306:A:G
Artery Aorta	eqtl	1.5e-11	-1.19	2:96082306:A:G
Thyroid	eqtl	7.6e-10	-0.83	2:96082306:A:G
Nerve Tibial	eqtl	1.5e-09	-0.81	2:96082306:A:G
Esophagus Mucosa	eqtl	3.0e-09	-0.84	2:96082306:A:G
Colon Sigmoid	eqtl	4.3e-09	-1.01	2:95815543:C:T
Testis	sqtl	5.0e-09	-0.63	2:96287095:A:G
Lung	eqtl	9.2e-08	-0.86	2:95815543:C:T
Cells Cultured fibroblasts	eqtl	1.0e-07	-0.74	2:96082306:A:G
Spleen	eqtl	1.9e-07	+0.66	2:96072112:C:T
Breast Mammary Tissue	eqtl	3.4e-07	-0.81	2:96082306:A:G

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	90.30	gold quality
right testis	UBERON:0004534	83.86	gold quality
heart left ventricle	UBERON:0002084	82.99	gold quality
left testis	UBERON:0004533	82.61	gold quality
testis	UBERON:0000473	82.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.73	gold quality
omental fat pad	UBERON:0010414	80.30	gold quality
adipose tissue	UBERON:0001013	78.28	gold quality
gastrocnemius	UBERON:0001388	77.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.31	gold quality
heart	UBERON:0000948	77.27	gold quality
lower esophagus	UBERON:0013473	77.21	gold quality
muscle of leg	UBERON:0001383	76.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.86	gold quality
spleen	UBERON:0002106	76.65	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.57	gold quality
thoracic mammary gland	UBERON:0005200	76.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	75.33	gold quality
right coronary artery	UBERON:0001625	75.17	gold quality
caudate nucleus	UBERON:0001873	74.92	gold quality
left coronary artery	UBERON:0001626	74.00	gold quality
putamen	UBERON:0001874	73.95	gold quality
left uterine tube	UBERON:0001303	73.69	gold quality
tibial nerve	UBERON:0001323	73.56	gold quality
fundus of stomach	UBERON:0001160	73.54	gold quality
mucosa of stomach	UBERON:0001199	73.50	gold quality
muscle tissue	UBERON:0002385	73.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.42	gold quality
skeletal muscle tissue	UBERON:0001134	73.36	gold quality
lymph node	UBERON:0000029	72.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.11	gold quality
right atrium auricular region	UBERON:0006631	71.67	gold quality
thoracic aorta	UBERON:0001515	71.30	gold quality
ascending aorta	UBERON:0001496	71.17	gold quality
granulocyte	CL:0000094	71.11	gold quality
minor salivary gland	UBERON:0001830	71.07	gold quality
body of stomach	UBERON:0001161	71.06	gold quality
descending thoracic aorta	UBERON:0002345	70.71	gold quality
saliva-secreting gland	UBERON:0001044	70.58	gold quality
nucleus accumbens	UBERON:0001882	70.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.97	gold quality
esophagus	UBERON:0001043	69.95	gold quality
colon	UBERON:0001155	69.92	gold quality
transverse colon	UBERON:0001157	69.78	gold quality
multicellular organism	UBERON:0000468	69.60	gold quality
body of uterus	UBERON:0009853	69.47	gold quality
tibial artery	UBERON:0007610	69.45	gold quality
popliteal artery	UBERON:0002250	69.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.40	gold quality
vermiform appendix	UBERON:0001154	69.38	gold quality
right lobe of thyroid gland	UBERON:0001119	69.33	gold quality
gall bladder	UBERON:0002110	69.32	gold quality
substantia nigra	UBERON:0002038	69.21	gold quality
right frontal lobe	UBERON:0002810	69.21	gold quality
smooth muscle tissue	UBERON:0001135	69.19	gold quality
intestine	UBERON:0000160	69.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.06	gold quality
frontal cortex	UBERON:0001870	69.03	gold quality
prefrontal cortex	UBERON:0000451	68.98	gold quality
stomach	UBERON:0000945	68.98	gold quality
small intestine	UBERON:0002108	68.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.81	gold quality
myometrium	UBERON:0001296	68.56	gold quality
cerebral cortex	UBERON:0000956	68.37	gold quality
endocervix	UBERON:0000458	68.35	gold quality
ectocervix	UBERON:0012249	68.35	gold quality
sural nerve	UBERON:0015488	68.34	silver quality
left lobe of thyroid gland	UBERON:0001120	68.13	gold quality
temporal lobe	UBERON:0001871	67.99	gold quality
anterior cingulate cortex	UBERON:0009835	67.88	gold quality
amygdala	UBERON:0001876	67.87	gold quality
right ovary	UBERON:0002118	67.87	gold quality
urinary bladder	UBERON:0001255	67.86	gold quality
thyroid gland	UBERON:0002046	67.81	gold quality
bone marrow cell	CL:0002092	67.68	silver quality
primary visual cortex	UBERON:0002436	67.35	gold quality
rectum	UBERON:0001052	67.25	gold quality
Ammon’s horn	UBERON:0001954	67.19	gold quality
body of pancreas	UBERON:0001150	67.10	gold quality
brain	UBERON:0000955	67.06	gold quality
left ovary	UBERON:0002119	66.77	gold quality
vagina	UBERON:0000996	66.73	gold quality
superior frontal gyrus	UBERON:0002661	66.65	gold quality
pancreas	UBERON:0001264	66.53	gold quality
ovary	UBERON:0000992	66.40	gold quality
fallopian tube	UBERON:0003889	66.35	gold quality
uterine cervix	UBERON:0000002	66.32	gold quality
calcaneal tendon	UBERON:0003701	66.14	gold quality
islet of Langerhans	UBERON:0000006	65.84	gold quality
placenta	UBERON:0001987	65.65	gold quality
bone marrow	UBERON:0002371	65.58	gold quality
upper lobe of left lung	UBERON:0008952	65.37	gold quality
metanephros cortex	UBERON:0010533	65.08	gold quality
tonsil	UBERON:0002372	65.00	gold quality
skin of leg	UBERON:0001511	64.97	gold quality
mucosa of transverse colon	UBERON:0004991	64.87	gold quality
zone of skin	UBERON:0000014	64.38	gold quality
cortical plate	UBERON:0005343	64.24	gold quality
hypothalamus	UBERON:0001898	64.23	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	323.63
E-ANND-3	yes	7.96
E-CURD-7	no	61.39
E-ENAD-21	no	61.39

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Epididymis	tissue	5.7	not detected
Choroid plexus	tissue	5.7
Tongue	tissue	4.5
Seminal vesicle	tissue	3.5	not detected
Basal ganglia	tissue	3.4	not detected
Testis	tissue	3.3	not detected
Spleen	tissue	2.8	not detected
Adipose tissue	tissue	2.7	not detected
Putamen	tissue	2.6
Tonsil	tissue	2.5	not detected
Ventral forebrain	tissue	2.4
Lymph node	tissue	2.1	not detected
Stomach 1	tissue	2.0	low
Smooth muscle	tissue	1.9	low
Spinal cord	tissue	1.9
Cerebellum	tissue	1.8	low
Vagina	tissue	1.7	not detected
Septum	tissue	1.7
Breast	tissue	1.6	not detected
Medulla oblongata	tissue	1.6
Placenta	tissue	1.5	not detected
Gallbladder	tissue	1.5	not detected
Corpus callosum	tissue	1.5
Periaqueductal gray	tissue	1.5
Rectum	tissue	1.4	not detected
Amygdala	tissue	1.4
Midbrain	tissue	1.4
Thalamus	tissue	1.4
Heart muscle	tissue	1.3	medium
Superior colliculi	tissue	1.3
Substantia nigra	tissue	1.3
Cerebral cortex	tissue	1.2	not detected
Pons	tissue	1.2
Urinary bladder	tissue	1.2	low
Bone marrow	tissue	1.2	not detected
Hippocampal formation	tissue	1.2
Retrosplenial cortex	tissue	1.2
Appendix	tissue	1.2	not detected
Occipital cortex	tissue	1.2
Insular cortex	tissue	1.2
Nucleus accumbens	tissue	1.1
Hypothalamus	tissue	1.1
Lung	tissue	1.1	not detected
Entorhinal cortex	tissue	1.1
Temporal cortex	tissue	1.1
Colon	tissue	1.0	low
Thymus	tissue	1.0
Retrosplenial and cingulate cortex	tissue	1.0
Olfactory bulb	tissue	1.0
Prefrontal cortex	tissue	0.9
Ovary	tissue	0.9	not detected
Motor cortex	tissue	0.9
Somatosensory cortex	tissue	0.9
Endometrium 1	tissue	0.8	not detected
Locus coeruleus	tissue	0.8
Adrenal gland	tissue	0.8	not detected
Postcentral gyrus	tissue	0.8
Pituitary gland	tissue	0.7
Small intestine	tissue	0.7	medium
Fallopian tube	tissue	0.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (3.4), Lateral geniculate body (3.0), Pulvinar (2.7), Habenula (2.3), Ventral posterolateral thalamic nucleus (2.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GPAT2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

15 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-2278	97.30	66.19	1130

Functional genomics

gnomAD constraint: pLI 3.02e-15, LOEUF 1.07, missense Z 1.36 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000434632 splits into 7 regions with different missense tolerance; 4 are missense-constrained (≈20% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:96,022,162–96,023,147	108 / 117.6	0.92	no
2:96,023,148–96,023,194	4 / 19.1	0.21	yes (p 5.4e-04)
2:96,023,195–96,025,489	295 / 305.5	0.97	no
2:96,025,490–96,025,541	4 / 19.1	0.21	yes (p 5.4e-04)
2:96,025,542–96,026,301	79 / 111.4	0.71	no
2:96,026,302–96,032,041	0 / 21.6	0.00	yes (p 3.3e-06)
2:96,032,042–96,032,359	21 / 71.6	0.29	yes (p 2.2e-09)
DepMap (CRISPR cell-line fitness): dependent in 32.1% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): VMRC-LCD (-2.649), HMY-1 (-1.335), PCI-30 (-1.329), HCC1143 (-1.326), NCI-H522 (-1.298), NCI-H23 (-1.192), NCI-H2030 (-1.165), 21NT (-1.097), KMRC-1 (-1.081), GSS (-1.073), H314 (-1.064), YD-8 (-1.048), KNS-81 (-1.04), D-502MG (-0.998), KMM-1 (-0.996).

Literature-anchored findings (GeneRIF, showing 1)

• GPAT2 as a cancer testis gene (PMID:24967918)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpat2	ENSDARG00000053575
mus_musculus	Gpat2	ENSMUSG00000046338
rattus_norvegicus	Gpat2	ENSRNOG00000013906
drosophila_melanogaster	mino	FBGN0027579
caenorhabditis_elegans		WBGENE00017261

Paralogs (2): GNPAT (ENSG00000116906), GPAM (ENSG00000119927)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2684962) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
small testis	1
male infertility	1
decreased testis weight	1
azoospermia	1
abnormal male germ cell morphology	1
abnormal spermatocyte morphology	1
abnormal DNA methylation during gametogenesis	1
increased male germ cell apoptosis	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
LINC00342	ncRNA	150759
ADRA2B	protein-coding	151
ASTL	protein-coding	431705
ANKRD36C	protein-coding	400986
DUSP2	protein-coding	1844

Protein

Protein identifiers

Glycerol-3-phosphate acyltransferase 2, mitochondrial — Q6NUI2 (reviewed: Q6NUI2)

Alternative names: 1-acylglycerol-3-phosphate O-acyltransferase GPAT2, xGPAT1

All UniProt accessions (3): C9JYV5, E9PE95, Q6NUI2

UniProt curated annotations — full annotation on UniProt →

Function. Transfers an acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate producing a lysophosphatidic acid (LPA), an essential step for the triacylglycerol (TAG) and glycerophospholipids. In vitro also transfers an acyl-group from acyl-ACP to the LPA producing a phosphatidic acid (PA). Prefers arachidonoyl-CoA as the acyl donor. Required for primary processing step during piRNA biosynthesis. Molecular mechanisms by which it promotes piRNA biosynthesis are unclear and do not involve its acyltransferase activity.

Subunit / interactions. Interacts with PIWIL2.

Subcellular location. Mitochondrion outer membrane.

Activity regulation. Inhibited by N-ethylmaleimide (NEM).

Domain organisation. The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for 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.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NUI2-1	1	yes
Q6NUI2-3	2
Q6NUI2-4	3
Q6NUI2-5	4

RefSeq proteins (10): NP_001308454, NP_001308455, NP_001308456, NP_001308457, NP_001308458, NP_001308459, NP_001308460, NP_001376568, NP_001409107, NP_001409108 (=MANE)

Domains & families (InterPro)

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

Pfam: 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)
• a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA (RHEA:19709)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37131)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CoA (RHEA:37443)
• (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + sn-glycerol 3-phosphate = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37463)

UniProt features (21 total): splice variant 5, modified residue 4, topological domain 3, sequence conflict 2, transmembrane region 2, region of interest 2, chain 1, short sequence motif 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUI2-F1	78.38	0.30

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH uncertain · 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.

Post-translational modifications (4)

Type	Positions
Phosphoserine	656, 662, 664
Phosphothreonine	660

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-1483166	Synthesis of PA	curated
R-HSA-75109	Triglyceride biosynthesis	curated
R-HSA-1483206	Glycerophospholipid biosynthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-1483257	Phospholipid metabolism	—
R-HSA-8979227	Triglyceride metabolism	—

MSigDB gene sets: 75 (showing top): E2F_Q4, E2F_Q4_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, E2F_Q3, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_UP, GOBP_NEUTRAL_LIPID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (8): glycerol-3-phosphate metabolic process (GO:0006072), glycerophospholipid metabolic process (GO:0006650), phosphatidic acid biosynthetic process (GO:0006654), CDP-diacylglycerol biosynthetic process (GO:0016024), triglyceride biosynthetic process (GO:0019432), piRNA processing (GO:0034587), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (4): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), glycerol-3-phosphate O-acyltransferase activity (GO:0004366), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Metabolism of lipids	2
Glycerophospholipid biosynthesis	1
Triglyceride metabolism	1
Phospholipid metabolism	1
Metabolism	1

GO top-level categories

21 GO namespaces:

Category	Terms
phospholipid metabolic process	2
glycerophospholipid biosynthetic process	2
alditol phosphate metabolic process	1
glycerolipid metabolic process	1
phosphatidic acid metabolic process	1
CDP-diacylglycerol metabolic process	1
triglyceride metabolic process	1
acylglycerol biosynthetic process	1
regulatory ncRNA processing	1
primary metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
acylglycerol O-acyltransferase activity	1
lysophosphatidic acid acyltransferase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
transferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrion	CC	high-throughput
glycerol-3-phosphate O-acyltransferase activity	MF	experiment

Protein interactions and networks

STRING

showing 15 of 614 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPAT2	GPAT3	Q53EU6	759
GPAT2	GPAT4	Q86UL3	754
GPAT2	AGPAT1	Q99943	618
GPAT2	AGPAT5	Q9NUQ2	608
GPAT2	TDRD9	Q8NDG6	596
GPAT2	AGPAT2	O15120	594
GPAT2	PLD6	Q8N2A8	586
GPAT2	AGPAT4	Q9NRZ5	566
GPAT2	LCLAT1	Q6UWP7	530
GPAT2	ASZ1	Q8WWH4	525
GPAT2	TDRD5	Q8NAT2	524
GPAT2	FKBP6	O75344	499
GPAT2	BTBD18	B2RXH4	499
GPAT2	DGAT2	Q96PD7	497
GPAT2	TDRKH	Q9Y2W6	497

IntAct

Human interaction partners of GPAT2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
BAG5	physical association	0.400	1

BioGRID (34 interactions; top human partners by supporting records): AKAP1 (Affinity Capture-MS), ASB14 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), C12orf74 (Affinity Capture-MS), CIB2 (Affinity Capture-MS), CIB3 (Affinity Capture-MS), D2HGDH (Affinity Capture-MS), DHFR (Affinity Capture-MS), F12 (Affinity Capture-MS), FAM57A (Affinity Capture-MS), FAM96A (Affinity Capture-MS), GPR182 (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), KLHL34 (Affinity Capture-MS), LDLRAD1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for GPAT2: 131 ClinVar records (3 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	105
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (3)

Showing all 3 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
3024503	NM_001321527.2(GPAT2):c.1156-1G>A	Likely pathogenic	criteria provided, single submitter	1
3024509	NM_001321527.2(GPAT2):c.1954C>T (p.Arg652Ter)	Likely pathogenic	criteria provided, single submitter	1
3024512	NM_001321527.2(GPAT2):c.1879C>T (p.Arg627Trp)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GPAT2’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; 38 predictions of 2,033):

Position(s)	Effect	Δscore	Sites
2:96022956–96022957	donor_loss	1.0000	5
2:96023181	acceptor_gain	1.0000
2:96024425–96024426	donor_loss	1.0000	4
2:96024771–96024772	donor_loss	1.0000	5
2:96023024–96023025	acceptor_loss	0.9900	5
2:96023184	acceptor_gain	0.9900
2:96024187–96024188	donor_loss	0.9900	5
2:96024338–96024339	acceptor_loss	0.9900	6
2:96024426	donor_loss	0.9900
2:96024844–96024845	acceptor_loss	0.9900	5

AlphaMissense

946 missense substitutions predicted likely pathogenic (of 5,143 scored), across 295 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
H449	8	0.880	0.940
D620	8	0.877	0.939
D494	8	0.863	0.928
D210	8	0.849	0.909
F382	8	0.832	0.977
D333	8	0.766	0.886
F497	7	0.961	0.995
C51	7	0.957	0.981
C54	7	0.947	0.969
F72	7	0.918	0.977
W88	7	0.913	0.974
F792	7	0.900	0.975
F550	7	0.892	0.946
F288	7	0.877	0.965
F689	7	0.875	0.950
S58	7	0.872	0.989
E80	7	0.860	0.929
C608	7	0.853	0.933
F250	7	0.852	0.955
F85	7	0.851	0.966

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:616431 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

GWAS associations

1 associations:

Study	Trait	p-value
GCST004280_91	Diastolic blood pressure	5e-12

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0006336	diastolic blood pressure

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cinnabarinic acid	decreases reaction, increases expression	1
GSK-J4	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
tebuconazole	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Nickel	increases expression	1
Valproic Acid	increases methylation	1
Oleic Acid	decreases reaction, increases expression	1
Palmitic Acid	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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

showing 60 of 133 trials:

NCT	Phase	Status	Title
NCT02202382	Phase 4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	Phase 4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	Phase 4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	Phase 4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	Phase 4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	Phase 3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	Phase 3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	Phase 3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	Phase 3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	Phase 3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	Phase 2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	Phase 2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	Phase 2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	Phase 2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	Phase 2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	Phase 2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	Phase 1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	Phase 1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	Phase 1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	Phase 2/3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	Phase 2/3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	Phase 2/3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	Phase 2/3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT07669402	Phase 2/3	COMPLETED	Comparative Evaluation of the Efficacy of Letrozole, L-Carnitine, and Their Combination on Sperm Quality, Oxidative Stress, and ART Outcomes in Men With Idiopathic Oligoasthenoteratozoospermia.
NCT02025270	Phase 1/2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	Early Phase 1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	Early Phase 1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	Early Phase 1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia
NCT01232465	Not specified	COMPLETED	Impact of Sperm DNA Integrity on In Vitro Cycles
NCT01255397	Not specified	UNKNOWN	Proposed Research Protocol For Male Infertility
NCT01346631	Not specified	WITHDRAWN	The Paleolithic Diet and Male Factor Infertility
NCT01407484	Not specified	COMPLETED	Male Infertility Related With Post Infection Inflammatory Syndrome
NCT01856361	Not specified	TERMINATED	Ramipril for the Treatment of Oligospermia
NCT01859520	Not specified	COMPLETED	Swim up and Gradient Methods Used in Assisted Reproduction Techniques on DNA Fragmentation of Spermatozoa
NCT01974947	Not specified	COMPLETED	Metabolic Syndrome and Male Infertility
NCT02006446	Not specified	COMPLETED	Relationship Between Sperm Head Vacuoles and Sperm DNA Alterations in Infertile Men
NCT02062229	Not specified	UNKNOWN	Oxidative Stress and Lipidomics in Male Infertility
NCT02107521	Not specified	TERMINATED	IMSI in Couples With Previous Implantation Failures
NCT02166567	Not specified	COMPLETED	Effect of Sorting of Apoptotic Spermatozoa on the Outcome of Assisted Reproduction
NCT02268123	Not specified	COMPLETED	Correlating In Vitro Fertilization Outcomes After Euploid Blastocyst Transfer With Sperm DNA Fragmentation
NCT02272439	Not specified	COMPLETED	Endocrine Disrupting Chemicals: Potential Effects on Male and Female Reproductive Health in Saskatchewan
NCT02756923	Not specified	COMPLETED	Regulation of Stem Spermatogonia in the Mature Testis
NCT02839447	Not specified	WITHDRAWN	A Clinical Evaluation of Semen Quality Using the MiOXSYS™ System 2.0
NCT02864329	Not specified	COMPLETED	Small RNA Pathways in Mammalian Gametogenesis
NCT02889341	Not specified	COMPLETED	Valuation of Variable Dose of Docosahexanoic Acid for the Improvement of the Parameters of Male Fertility
NCT02931721	Not specified	COMPLETED	Treatment of Severe Male Infertility - Predictive Factors (Imaging)
NCT03167008	Not specified	UNKNOWN	Vitamin D Level vs Semen Parameters