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
• Clinical variants (ClinVar): 115 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001244949

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: 15 — 13 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000348367, ENST00000369425, ENST00000480130, ENST00000498541, ENST00000901835, ENST00000901836, ENST00000901837, ENST00000901838, ENST00000901839, ENST00000901840, ENST00000901841, ENST00000901842, ENST00000901843, ENST00000901844, ENST00000964625

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.

FANTOM5 promoters (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

255 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

158 targeting GPAM, 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-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

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)

Protein

Protein identifiers

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

All UniProt accessions (2): Q9HCL2, Q5VW52

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), 7 shown:

• 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 (94 total): helix 32, 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.

PDB	Method	Resolution (Å)
8E4Y	ELECTRON MICROSCOPY	3.4
8E50	ELECTRON MICROSCOPY	3.67

Predicted structure (AlphaFold)

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

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): 288; 293; 328; 462; 278; 279

Post-translational modifications (5): 380, 688, 695, 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

6 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-75109	Triglyceride biosynthesis
R-HSA-8931987	RUNX1 regulates estrogen receptor mediated transcription
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

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 (21): regulation of cytokine production (GO:0001817), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), glycerophospholipid metabolic process (GO:0006650), diacylglycerol biosynthetic process (GO:0006651), phosphatidic acid biosynthetic process (GO:0006654), phosphatidylglycerol biosynthetic process (GO:0006655), activation-induced cell death of T cells (GO:0006924), response to glucose (GO:0009749), CDP-diacylglycerol biosynthetic process (GO:0016024), triglyceride biosynthetic process (GO:0019432), positive regulation of multicellular organism growth (GO:0040018), positive regulation of activated T cell proliferation (GO:0042104), activated T cell proliferation (GO:0050798), defense response to virus (GO:0051607), fatty acid homeostasis (GO:0055089), phospholipid homeostasis (GO:0055091), negative regulation of activation-induced cell death of T cells (GO:0070236), lipid metabolic process (GO:0006629), triglyceride metabolic process (GO:0006641), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (5): glycerol-3-phosphate O-acyltransferase activity (GO:0004366), protein binding (GO:0005515), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), plasma membrane (GO:0005886), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycerophospholipid biosynthetic process	3
acylglycerol biosynthetic process	2
lipid homeostasis	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
phospholipid metabolic process	1
glycerolipid metabolic process	1
diacylglycerol metabolic process	1
phosphatidic acid metabolic process	1
phosphatidylglycerol metabolic process	1
T cell homeostasis	1
T cell apoptotic process	1
response to hexose	1
CDP-diacylglycerol metabolic process	1
triglyceride metabolic process	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
positive regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
T cell proliferation	1
defense response	1
response to virus	1
negative regulation of immune system process	1
activation-induced cell death of T cells	1
negative regulation of T cell apoptotic process	1
regulation of activation-induced cell death of T cells	1
primary metabolic process	1
acylglycerol metabolic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPAM	GPAT3	Q53EU6	945
GPAM	GPAT4	Q86UL3	910
GPAM	LPGAT1	Q92604	884
GPAM	SCD5	Q86SK9	859
GPAM	SCD	O00767	828
GPAM	AGPAT1	Q99943	755
GPAM	DGAT1	O75907	742
GPAM	FASN	P49327	726
GPAM	PPARA	Q07869	726
GPAM	AGPAT2	O15120	723
GPAM	DGAT2	Q96PD7	716
GPAM	PCK1	P35558	701
GPAM	ACACA	Q13085	701
GPAM	PPARG	P37231	693
GPAM	SREBF1	P36956	686

IntAct

28 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GPAM	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
GPAM	COQ9	psi-mi:“MI:0914”(association)	0.500
GPAM	COQ9	psi-mi:“MI:0915”(physical association)	0.500
GPAM	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
ATP2B2	GPR89A	psi-mi:“MI:0914”(association)	0.350
CDH5	ARVCF	psi-mi:“MI:0914”(association)	0.350
PSMC4	PSMD11	psi-mi:“MI:0914”(association)	0.350
SIRT2	DEGS1	psi-mi:“MI:0914”(association)	0.350
GPAM	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
ATAD3A	TMEM223	psi-mi:“MI:0914”(association)	0.350
ATP2B2	ESYT2	psi-mi:“MI:0914”(association)	0.350
CDH5	NBAS	psi-mi:“MI:0914”(association)	0.350
GPAM	SRC	psi-mi:“MI:0914”(association)	0.350
MTCH1	IPO5	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
CD226	TMED7-TICAM2	psi-mi:“MI:0914”(association)	0.350
FSD2	MYO9A	psi-mi:“MI:0914”(association)	0.350
NPTN	RIMOC1	psi-mi:“MI:0914”(association)	0.350
PBXIP1	CEBPZOS	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-29	psi-mi:“MI:0914”(association)	0.350
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350
GPAM	CIDEB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): GPAM (Affinity Capture-MS), GPAM (Reconstituted Complex), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), IDE (Affinity Capture-MS), ECH1 (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Affinity Capture-MS), GPAM (Biochemical Activity)

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: A0L2D7, A1AIL8, A1RE94, A1SBC6, A4IF87, A4W5F4, A4XWX9, A4YC03, A5W867, A6TGV0, A6V1B5, A6VQ68, A7ZUR3, A8A7E1, A8H9R9, A9MGP8, A9N1L4, B0KS79, B0TNU4, B0U229, B1IUL1, B1JBS6, B1LPK6, B1XC40, B2HNJ0, B2I7N1, B2TX75, B4EYR5, B4T1T0, B4TDL8, B4TQQ3, B5BJV8, B5F1Q4, B5FQQ9, B5QZ60, B5R7T4, B5XXZ1, B5Z182, B6I5Q6, B7LAY9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

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)

Variant ID	HGVS	Classification
4083503	GRCh37/hg19 10q25.2-25.3(chr10:113914387-115668295)x1	Pathogenic

SpliceAI

2961 predictions. Top by Δscore:

Variant	Effect	Δscore
10:112155858:A:C	donor_gain	1.0000
10:112157396:C:CT	acceptor_gain	1.0000
10:112158310:TCTTA:T	donor_loss	1.0000
10:112158311:CTTAC:C	donor_loss	1.0000
10:112158312:TTAC:T	donor_loss	1.0000
10:112158313:TA:T	donor_loss	1.0000
10:112158314:A:AG	donor_loss	1.0000
10:112158315:C:CT	donor_loss	1.0000
10:112159908:CA:C	donor_loss	1.0000
10:112159909:A:AC	donor_gain	1.0000
10:112159909:A:AT	donor_loss	1.0000
10:112159909:AC:A	donor_gain	1.0000
10:112159910:C:CC	donor_gain	1.0000
10:112159910:CC:C	donor_gain	1.0000
10:112159910:CCA:C	donor_gain	1.0000
10:112159910:CCAG:C	donor_gain	1.0000
10:112159910:CCAGT:C	donor_gain	1.0000
10:112160049:GCAAG:G	acceptor_gain	1.0000
10:112160050:CAAG:C	acceptor_gain	1.0000
10:112160050:CAAGC:C	acceptor_gain	1.0000
10:112160051:AAG:A	acceptor_gain	1.0000
10:112160052:AG:A	acceptor_gain	1.0000
10:112160054:C:CC	acceptor_gain	1.0000
10:112160766:C:CT	donor_gain	1.0000
10:112160767:T:TT	donor_gain	1.0000
10:112160867:CC:C	acceptor_gain	1.0000
10:112160868:CC:C	acceptor_gain	1.0000
10:112160868:CCTAA:C	acceptor_loss	1.0000
10:112161662:CATA:C	donor_loss	1.0000
10:112161663:ATACC:A	donor_loss	1.0000

AlphaMissense

5445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:112166433:C:G	R397P	1.000
10:112160657:A:G	L569P	0.999
10:112160757:C:G	A536P	0.999
10:112160788:G:C	F525L	0.999
10:112160788:G:T	F525L	0.999
10:112160790:A:G	F525L	0.999
10:112160792:C:T	G524E	0.999
10:112160793:C:A	G524W	0.999
10:112160793:C:G	G524R	0.999
10:112160793:C:T	G524R	0.999
10:112161695:G:T	A489D	0.999
10:112161712:C:A	M483I	0.999
10:112161712:C:G	M483I	0.999
10:112161712:C:T	M483I	0.999
10:112166436:A:T	V396D	0.999
10:112168356:A:G	S355P	0.999
10:112168932:C:T	G272E	0.999
10:112172215:G:T	A254D	0.999
10:112172272:T:A	D235V	0.999
10:112172272:T:G	D235A	0.999
10:112172273:C:A	D235Y	0.999
10:112172273:C:G	D235H	0.999
10:112172282:A:G	S232P	0.999
10:112154680:A:C	S773R	0.998
10:112154680:A:T	S773R	0.998
10:112154682:T:G	S773R	0.998
10:112160783:C:T	G527E	0.998
10:112160789:A:G	F525S	0.998
10:112161686:A:G	L492P	0.998
10:112161689:A:G	L491P	0.998

dbSNP variants (sampled 300 via entrez): RS1000049470 (10:112200379 C>G), RS1000100069 (10:112200732 T>C), RS1000167866 (10:112195162 A>G), RS1000212317 (10:112158209 G>A,T), RS1000252104 (10:112189106 G>T), RS1000309543 (10:112162657 T>C), RS1000317620 (10:112202029 T>C), RS1000323795 (10:112194334 C>A,T), RS1000351674 (10:112202318 T>C,G), RS1000360770 (10:112158462 T>A,C), RS1000375951 (10:112158144 T>C), RS1000389730 (10:112215155 G>A,C), RS1000405443 (10:112171376 A>ATCT), RS1000644994 (10:112161234 T>C,G), RS1000682530 (10:112167194 C>T)

Disease associations

OMIM: gene MIM:602395 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

66 associations (top):

Study	Trait	p-value
GCST000759_34	LDL cholesterol	2.000000e-09
GCST000760_13	Cholesterol, total	2.000000e-10
GCST002221_52	Cholesterol, total	7.000000e-16
GCST002222_40	LDL cholesterol	1.000000e-13
GCST002896_23	Cholesterol, total	8.000000e-10
GCST002898_6	LDL cholesterol	5.000000e-07
GCST002899_37	HDL cholesterol	7.000000e-09
GCST004233_55	LDL cholesterol levels	1.000000e-15
GCST004235_61	Total cholesterol levels	2.000000e-18
GCST005998_22	Alanine transaminase levels	2.000000e-09
GCST006005_7	High density lipoprotein cholesterol levels	8.000000e-13
GCST006016_18	Serum alkaline phosphatase levels	2.000000e-10
GCST006034_41	Total cholesterol levels	6.000000e-10
GCST006611_143	HDL cholesterol	6.000000e-21
GCST006612_42	LDL cholesterol	2.000000e-18
GCST006614_10	Total cholesterol levels	1.000000e-12
GCST008070_132	HDL cholesterol levels	9.000000e-07
GCST008070_60	HDL cholesterol levels	1.000000e-16
GCST008070_93	HDL cholesterol levels	1.000000e-07
GCST008074_147	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-12
GCST008074_16	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-06
GCST008074_52	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-07
GCST008075_168	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-27
GCST008075_222	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-07
GCST008075_42	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-15
GCST008077_88	LDL cholesterol levels	6.000000e-06
GCST008078_110	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-13
GCST008078_37	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-08
GCST008079_157	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-14
GCST008079_60	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-10

EFO canonical traits (12, from GWAS)

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 (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, increases expression, decreases reaction, affects expression, affects cotreatment	4
Benzo(a)pyrene	affects cotreatment, decreases expression, increases methylation	4
Cyclosporine	affects expression, decreases expression	4
Acetaminophen	decreases expression	3
Valproic Acid	affects methylation, decreases expression, affects expression	3
sodium arsenite	decreases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Dexamethasone	increases expression, affects cotreatment	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 methylation, decreases expression	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	affects cotreatment, decreases reaction, increases expression	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)

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