AGPAT3

Summary

AGPAT3 (1-acylglycerol-3-phosphate O-acyltransferase 3, HGNC:326) is a protein-coding gene on chromosome 21q22.3, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (Q9NRZ7). Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.

The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 56894 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 58 total — 3 pathogenic
• MANE Select transcript: NM_020132

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:326
Approved symbol	AGPAT3
Name	1-acylglycerol-3-phosphate O-acyltransferase 3
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	LPAAT-gamma, LPAAT3, LPLAT3
Ensembl gene	ENSG00000160216
Ensembl biotype	protein_coding
OMIM	614794
Entrez	56894

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000291572, ENST00000327505, ENST00000398058, ENST00000398061, ENST00000398063, ENST00000422850, ENST00000445582, ENST00000448287, ENST00000448845, ENST00000457068, ENST00000467358, ENST00000474735, ENST00000479117, ENST00000481319, ENST00000484865, ENST00000497909, ENST00000498670, ENST00000546158

RefSeq mRNA: 5 — MANE Select: NM_020132 NM_001037553, NM_001369878, NM_001369880, NM_001369881, NM_020132

CCDS: CCDS13703

Canonical transcript exons

ENST00000291572 — 10 exons

Exon	Start	End
ENSE00001137610	43903957	43904019
ENSE00001414183	43959634	43959859
ENSE00001950544	43865223	43865345
ENSE00003500378	43978046	43978121
ENSE00003532414	43967946	43968115
ENSE00003620755	43970653	43970806
ENSE00003635589	43969118	43969279
ENSE00003671315	43980989	43981187
ENSE00003790142	43971388	43971490
ENSE00003844654	43982304	43987592

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 96.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6037 / max 109.2376, expressed in 1795 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189403	6.3708	1720
189401	4.1916	1635
189402	1.0686	767
189410	0.4129	71
189408	0.2749	120
189405	0.1585	37
189404	0.0796	31
189406	0.0284	17
189416	0.0184	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	96.08	gold quality
middle temporal gyrus	UBERON:0002771	95.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.94	gold quality
entorhinal cortex	UBERON:0002728	95.39	gold quality
postcentral gyrus	UBERON:0002581	95.31	gold quality
primary visual cortex	UBERON:0002436	95.19	gold quality
parotid gland	UBERON:0001831	95.08	gold quality
parietal lobe	UBERON:0001872	95.07	gold quality
jejunal mucosa	UBERON:0000399	94.95	gold quality
subthalamic nucleus	UBERON:0001906	94.87	gold quality
endothelial cell	CL:0000115	94.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.57	gold quality
globus pallidus	UBERON:0001875	94.52	gold quality
gastrocnemius	UBERON:0001388	94.38	gold quality
ventral tegmental area	UBERON:0002691	94.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.34	gold quality
medial globus pallidus	UBERON:0002477	94.32	gold quality
inferior vagus X ganglion	UBERON:0005363	94.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.15	gold quality
spinal cord	UBERON:0002240	94.09	gold quality
monocyte	CL:0000576	94.07	gold quality
temporal lobe	UBERON:0001871	94.05	gold quality
muscle of leg	UBERON:0001383	93.85	gold quality
superior frontal gyrus	UBERON:0002661	93.84	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.80	gold quality
body of tongue	UBERON:0011876	93.66	gold quality
superior vestibular nucleus	UBERON:0007227	93.54	gold quality
occipital lobe	UBERON:0002021	93.52	gold quality
pons	UBERON:0000988	93.24	gold quality
right lobe of liver	UBERON:0001114	93.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	no	871.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

155 targeting AGPAT3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611

Literature-anchored findings (GeneRIF, showing 5)

• Of the two well conserved acyltransferase motifs, NHX(4)D is present in AGPAT8, whereas arginine in the EGTR motif is substituted by aspartate. (PMID:16620771)
• Results report the identification of an integral membrane lysophosphatidic acid-specific acyltransferase, LPAAT3, which regulates Golgi membrane tubule formation, trafficking, and structure by altering phospholipids and lysophospholipids. (PMID:19635840)
• The data is consistent with a structural arrangement in which motif I is located in the cytoplasm and motif II is in the endoplasmic reticulum and Golgi lumen, suggesting a different model for AGPAT3/LPAAT3’s enzymatic mechanism. (PMID:20537980)
• enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5 (PMID:21173190)
• A loss of function variant in AGPAT3 underlies intellectual disability and retinitis pigmentosa (IDRP) syndrome. (PMID:37821758)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	agpat3	ENSDARG00000036549
mus_musculus	Agpat3	ENSMUSG00000001211
rattus_norvegicus	Agpat3	ENSRNOG00000001205
drosophila_melanogaster	Agpat4	FBGN0036622
drosophila_melanogaster	Agpat3	FBGN0036623

Paralogs (4): AGPAT4 (ENSG00000026652), LPGAT1 (ENSG00000123684), AGPAT5 (ENSG00000155189), LCLAT1 (ENSG00000172954)

Protein

Protein identifiers

1-acyl-sn-glycerol-3-phosphate acyltransferase gamma — Q9NRZ7 (reviewed: Q9NRZ7)

Alternative names: 1-acylglycerol-3-phosphate O-acyltransferase 3, Lysophosphatidic acid acyltransferase gamma

All UniProt accessions (5): Q9NRZ7, C9J184, C9JK35, C9JL26, C9JQX8

UniProt curated annotations — full annotation on UniProt →

Function. Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. Acts on LPA containing saturated or unsaturated fatty acids C16:0-C20:4 at the sn-1 position using C18:1, C20:4 or C18:2-CoA as the acyl donor. Also acts on lysophosphatidylcholine, lysophosphatidylinositol and lysophosphatidylserine using C18:1 or C20:4-CoA. Has a preference for arachidonoyl-CoA as a donor. Also has a modest lysophosphatidylinositol acyltransferase (LPIAT) activity, converts lysophosphatidylinositol (LPI) into phosphatidylinositol.

Subcellular location. Endoplasmic reticulum membrane. Nucleus envelope.

Tissue specificity. Widely expressed with highest levels in testis, pancreas and kidney, followed by spleen, lung, adipose tissue and liver.

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 2/3.

Similarity. Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NRZ7-1	1, Gamma-1	yes
Q9NRZ7-2	2, Gamma-2
Q9NRZ7-3	3

RefSeq proteins (5): NP_001032642, NP_001356807, NP_001356809, NP_001356810, NP_064517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002123	Plipid/glycerol_acylTrfase	Domain
IPR032098	Acyltransf_C	Domain

Pfam: PF01553, PF16076

Enzyme classification (BRENDA):

• EC 2.3.1.51 — 1-acylglycerol-3-phosphate O-acyltransferase (BRENDA: 39 organisms, 381 substrates, 31 inhibitors, 32 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-ACYL-SN-GLYCEROL 3-PHOSPHATE	0.0053–0.125	8
OLEOYL-COA	0.0027–0.0215	8
PALMITOYL-COA	0.0014–0.012	8
1-OLEOYL-SN-GLYCEROL 3-PHOSPHATE	0.0048–0.018	5
1-PALMITOYL-SN-GLYCEROL 3-PHOSPHATE	0.003	1
DOCOSAHEXAENOYL-COA	0.0138	1
PAMITOLEOYL-COA	0.0368	1

Catalyzed reactions (Rhea), 12 shown:

• a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA (RHEA:19709)
• 1-hexadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:33187)
• 1-hexadecanoyl-sn-glycero-3-phosphate + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + CoA (RHEA:35915)
• a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol) + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = a 1-acyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + CoA (RHEA:37015)
• 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 + octadecanoyl-CoA = 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37147)
• heptadecanoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-heptadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37155)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (9Z,12Z)-octadecadienoyl-CoA = 1-(9Z)-octadecenoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + CoA (RHEA:37159)
• 1-octadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37163)
• pentadecanoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-pentadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37175)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-L-serine + CoA (RHEA:37379)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-icosatetraenoyl-sn-glycero-3-phosphocholine + CoA (RHEA:37395)

UniProt features (11 total): topological domain 3, sequence conflict 2, transmembrane region 2, splice variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRZ7-F1	94.63	0.94

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic

MSigDB gene sets: 212 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_LIPID_BIOSYNTHETIC_PROCESS, BERNARD_PPAPDC1B_TARGETS_UP, MCCABE_HOXC6_TARGETS_CANCER_UP, chr21q22

GO Biological Process (4): phosphatidic acid biosynthetic process (GO:0006654), phospholipid biosynthetic process (GO:0008654), CDP-diacylglycerol biosynthetic process (GO:0016024), lipid metabolic process (GO:0006629)

GO Molecular Function (5): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), lysophosphatidic acid acyltransferase activity (GO:0042171)

GO Cellular Component (8): Golgi membrane (GO:0000139), nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycerophospholipid biosynthetic process	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
phosphatidic acid metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
CDP-diacylglycerol metabolic process	1
primary metabolic process	1
acylglycerol O-acyltransferase activity	1
lysophosphatidic acid acyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
lysophospholipid acyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
nucleus	1
organelle envelope	1
cytoplasm	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGPAT3	AGPAT1	Q99943	803
AGPAT3	GPAT4	Q86UL3	736
AGPAT3	AGPAT2	O15120	717
AGPAT3	GPAT3	Q53EU6	693
AGPAT3	GPAM	Q9HCL2	682
AGPAT3	LPCAT4	Q643R3	636
AGPAT3	DGAT2	Q96PD7	612
AGPAT3	MOGAT1	Q96PD6	608
AGPAT3	LPIN3	Q9BQK8	572
AGPAT3	LPCAT1	Q8NF37	555
AGPAT3	MBOAT2	Q6ZWT7	530
AGPAT3	DGAT1	O75907	526
AGPAT3	LPCAT2	Q7L5N7	511
AGPAT3	LPCAT3	Q6P1A2	497
AGPAT3	MOGAT2	Q3SYC2	493

IntAct

111 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
AGPAT3	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
NKAPD1	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
SREK1IP1	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
MPP1	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
BNIP2	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
FAM133A	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
AGPAT3	TMX2	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
AQP6	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
TMEM167B	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
GOLT1A	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
HSD17B11	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
HSD17B13	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
MFSD14B	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
SLC35C2	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	AGPAT3	psi-mi:“MI:0915”(physical association)	0.560
AGPAT3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
FAM241A	SPTLC2	psi-mi:“MI:0914”(association)	0.530
AGPAT3	ENDOD1	psi-mi:“MI:0914”(association)	0.530
MMAB	PMPCB	psi-mi:“MI:0914”(association)	0.530

BioGRID (128): AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Two-hybrid), TOM1L1 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS)

ESM2 similar proteins: A2VE61, A5PLL7, A6QLM0, B1AZA5, B8BIM2, D3ZXD8, E9PTA2, O35052, O75907, O94759, P48631, P52848, P98191, Q02353, Q05B45, Q0P5C0, Q0VCJ8, Q2QZ14, Q3UHN9, Q4R4U1, Q4R766, Q5EA70, Q5HZE2, Q5R5F8, Q5R7B1, Q61115, Q6DD32, Q6NYY9, Q6P360, Q6PHN7, Q84VT2, Q8BFQ2, Q8C1E7, Q8GZC3, Q8MK44, Q8NBD8, Q8NBT3, Q8VWZ8, Q90693, Q91YD4

Diamond homologs: Q20800, Q3UN02, Q41745, Q5F3X0, Q5RA57, Q6NYV8, Q6UWP7, Q8L4Y2, Q9LHN4, Q9NRZ7, P33333, Q4R581, Q5E9R2, Q5R757, Q6IWY1, Q8K4X7, Q8LG50, Q924S1, Q9D1E8, Q9D517, Q9NRZ5, Q9NUQ2, Q9SYC8, Q9XFW4, Q9US20, O94361, Q12185, A8J0J0, O15120, O25903, O35083, P44848, Q22267, Q2YQS9, Q42670, Q42868, Q42870, Q8K3K7, Q95JH0, Q95JH2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AGPAT3	“down-regulates quantity”	“1-acyl-sn-glycerol 3-phosphate(2-)”	“chemical modification”
AGPAT3	up-regulates	“phosphatidic acid”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425366	8	29.0×	3e-08
SLC-mediated transmembrane transport	9	10.7×	9e-06
Transport of small molecules	12	6.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	5	19.0×	2e-03
transmembrane transport	5	10.3×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	36
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2504577	NM_020132.5(AGPAT3):c.747C>A (p.Tyr249Ter)	Pathogenic
647965	NC_000021.8:g.(?43892908)(45629566_?)del	Pathogenic
688323	GRCh37/hg19 21q22.3(chr21:43756585-46240105)x1	Pathogenic

SpliceAI

3497 predictions. Top by Δscore:

Variant	Effect	Δscore
21:43881157:A:T	donor_gain	1.0000
21:43889264:C:G	donor_gain	1.0000
21:43959855:GAGCC:G	donor_gain	1.0000
21:43959857:GCC:G	donor_gain	1.0000
21:43959860:G:GG	donor_gain	1.0000
21:43961279:T:G	acceptor_gain	1.0000
21:43969117:GA:G	acceptor_gain	1.0000
21:43969275:TGTGG:T	donor_loss	1.0000
21:43969276:GTGG:G	donor_gain	1.0000
21:43969278:GG:G	donor_gain	1.0000
21:43969279:GG:G	donor_gain	1.0000
21:43969280:G:GG	donor_gain	1.0000
21:43969280:GTGA:G	donor_loss	1.0000
21:43969282:GAGT:G	donor_loss	1.0000
21:43970651:A:AG	acceptor_gain	1.0000
21:43970652:G:GG	acceptor_gain	1.0000
21:43970652:GTT:G	acceptor_gain	1.0000
21:43970652:GTTT:G	acceptor_gain	1.0000
21:43970786:TC:T	donor_gain	1.0000
21:43971386:A:AG	acceptor_gain	1.0000
21:43971386:AGTC:A	acceptor_gain	1.0000
21:43971387:G:GT	acceptor_gain	1.0000
21:43971387:GT:G	acceptor_gain	1.0000
21:43971387:GTC:G	acceptor_gain	1.0000
21:43971387:GTCG:G	acceptor_gain	1.0000
21:43971387:GTCGC:G	acceptor_gain	1.0000
21:43971488:GAGGT:G	donor_loss	1.0000
21:43971489:AGGT:A	donor_loss	1.0000
21:43971492:T:A	donor_loss	1.0000
21:43865343:CAG:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000029972 (21:43940598 G>A), RS1000043612 (21:43870248 C>G), RS1000071521 (21:43976496 G>A), RS1000080198 (21:43940860 C>G), RS1000080223 (21:43903898 C>G), RS1000136787 (21:43906765 T>G), RS1000136922 (21:43937490 C>T), RS1000204592 (21:43892314 A>C), RS1000227397 (21:43913787 G>C), RS1000242803 (21:43979783 C>G), RS1000255516 (21:43946926 G>A,T), RS1000280895 (21:43885987 A>G), RS1000296482 (21:43979240 C>T), RS1000330048 (21:43875316 A>C), RS1000371550 (21:43880527 G>T)

Disease associations

OMIM: gene MIM:614794 | disease phenotypes: MIM:616341, MIM:254800, MIM:244400

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (5): intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 30 (MONDO:0014595), progressive myoclonus epilepsy (MONDO:0020074), primary ciliary dyskinesia (MONDO:0016575), neurodevelopmental disorder (MONDO:0700092)

Orphanet (4): Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261), Primary ciliary dyskinesia (Orphanet:244), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001179_9	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	2.000000e-07
GCST008746_35	Estimated glomerular filtration rate in diabetes	1.000000e-12
GCST009028_21	Adverse response to drug	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006809	docosapentaenoic acid measurement
EFO:0009658	adverse effect

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Valproic Acid	increases expression, increases methylation	3
Cyclosporine	decreases methylation, decreases expression	3
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Arbutin	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1PT	HAP1 AGPAT3 (-) 1	Cancer cell line	Male
CVCL_E1PU	HAP1 AGPAT3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders