AGPAT5

Summary

AGPAT5 (1-acylglycerol-3-phosphate O-acyltransferase 5, HGNC:20886) is a protein-coding gene on chromosome 8p23.1, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon (Q9NUQ2). 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.

This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. A pseudogene of this gene is present on the Y chromosome.

Source: NCBI Gene 55326 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 159 total — 59 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_018361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20886
Approved symbol	AGPAT5
Name	1-acylglycerol-3-phosphate O-acyltransferase 5
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11210, LPAAT-e, LPAAT-epsilon, LPLAT5
Ensembl gene	ENSG00000155189
Ensembl biotype	protein_coding
OMIM	614796
Entrez	55326

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000285518, ENST00000518327, ENST00000523234, ENST00000523586, ENST00000530716, ENST00000533159, ENST00000533648, ENST00000901527, ENST00000901528, ENST00000927031, ENST00000927032, ENST00000927033, ENST00000958247, ENST00000958248

RefSeq mRNA: 1 — MANE Select: NM_018361 NM_018361

CCDS: CCDS34796

Canonical transcript exons

ENST00000285518 — 8 exons

Exon	Start	End
ENSE00001019595	6757163	6761503
ENSE00001282669	6708642	6708887
ENSE00003499275	6741661	6741751
ENSE00003530669	6747670	6747828
ENSE00003557485	6732561	6732650
ENSE00003587374	6724870	6724939
ENSE00003587819	6730711	6730826
ENSE00003671312	6755051	6755174

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 95.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2191 / max 457.1371, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87252	19.3181	1793
87249	9.9264	1644
87253	2.6564	897
87251	0.2460	115
87250	0.0711	21
87262	0.0011	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	95.24	gold quality
ventricular zone	UBERON:0003053	95.00	gold quality
cortical plate	UBERON:0005343	93.89	gold quality
embryo	UBERON:0000922	92.77	gold quality
ganglionic eminence	UBERON:0004023	92.77	gold quality
adrenal tissue	UBERON:0018303	92.18	gold quality
left testis	UBERON:0004533	92.03	gold quality
right testis	UBERON:0004534	91.64	gold quality
testis	UBERON:0000473	91.49	gold quality
endometrium	UBERON:0001295	91.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.05	gold quality
calcaneal tendon	UBERON:0003701	90.53	gold quality
caudate nucleus	UBERON:0001873	87.92	gold quality
islet of Langerhans	UBERON:0000006	87.77	gold quality
nucleus accumbens	UBERON:0001882	87.76	gold quality
putamen	UBERON:0001874	87.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.57	gold quality
temporal lobe	UBERON:0001871	87.34	gold quality
amygdala	UBERON:0001876	87.34	gold quality
rectum	UBERON:0001052	87.08	gold quality
substantia nigra	UBERON:0002038	87.02	gold quality
superior frontal gyrus	UBERON:0002661	86.73	gold quality
hypothalamus	UBERON:0001898	86.42	gold quality
Ammon’s horn	UBERON:0001954	86.34	gold quality
prefrontal cortex	UBERON:0000451	86.33	gold quality
placenta	UBERON:0001987	86.20	gold quality
anterior cingulate cortex	UBERON:0009835	85.75	gold quality
cerebral cortex	UBERON:0000956	85.68	gold quality
brain	UBERON:0000955	85.45	gold quality
muscle tissue	UBERON:0002385	85.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

143 targeting AGPAT5, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192

Literature-anchored findings (GeneRIF, showing 2)

• This publication describes the molecular cloning, tissue distribution, and enzyme characterization of the mouse homolog, mAGPAT5. (PMID:15367102)
• enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5 (PMID:21173190)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	agpat5	ENSDARG00000063187
mus_musculus	Agpat5	ENSMUSG00000031467
rattus_norvegicus	Agpat5	ENSRNOG00000080701
caenorhabditis_elegans	acl-11	WBGENE00017888

Paralogs (4): AGPAT4 (ENSG00000026652), LPGAT1 (ENSG00000123684), AGPAT3 (ENSG00000160216), LCLAT1 (ENSG00000172954)

Protein

Protein identifiers

1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon — Q9NUQ2 (reviewed: Q9NUQ2)

Alternative names: 1-acylglycerol-3-phosphate O-acyltransferase 5, Lysophosphatidic acid acyltransferase epsilon

All UniProt accessions (5): Q9NUQ2, A0A024R640, E5RH21, H0YAW1, H0YC22

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 C15:0-C20:4 at the sn-1 position using C18:1-CoA as the acyl donor. Also acts on lysophosphatidylethanolamine using oleoyl-CoA, but not arachidonoyl-CoA, and lysophosphatidylinositol using arachidonoyl-CoA, but not oleoyl-CoA. Activity toward lysophosphatidylglycerol not detectable.

Subcellular location. Endoplasmic reticulum membrane. Nucleus envelope. Mitochondrion.

Tissue specificity. Widely expressed.

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.

RefSeq proteins (1): NP_060831* (*=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-(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)
• 1-heptadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-heptadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phosphate + CoA (RHEA:37151)
• heptadecanoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-heptadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37155)
• 1-octadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37163)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + tetradecanoyl-CoA = 1-(9Z)-octadecenoyl-2-tetradecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37171)
• 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 + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + CoA (RHEA:37387)
• 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 (7 total): transmembrane region 3, chain 1, short sequence motif 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUQ2-F1	94.23	0.89

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA

MSigDB gene sets: 222 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GTGCCTT_MIR506, MODULE_205

GO Biological Process (7): hematopoietic progenitor cell differentiation (GO:0002244), acylglycerol metabolic process (GO:0006639), phosphatidic acid biosynthetic process (GO:0006654), phospholipid biosynthetic process (GO:0008654), CDP-diacylglycerol biosynthetic process (GO:0016024), phosphatidylinositol acyl-chain remodeling (GO:0036149), lipid metabolic process (GO:0006629)

GO Molecular Function (4): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), acyltransferase activity (GO:0016746), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): nuclear envelope (GO:0005635), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endomembrane system (GO:0012505), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
glycerophospholipid biosynthetic process	2
endomembrane system	2
cytoplasm	2
cellular anatomical structure	2
hemopoiesis	1
cell differentiation	1
neutral lipid metabolic process	1
glycerolipid metabolic process	1
phosphatidic acid metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
CDP-diacylglycerol metabolic process	1
phosphatidylinositol metabolic process	1
primary metabolic process	1
acylglycerol O-acyltransferase activity	1
lysophosphatidic acid acyltransferase activity	1
transferase activity	1
binding	1
catalytic activity	1
nucleus	1
organelle envelope	1
nuclear lumen	1
intracellular membraneless organelle	1
mitochondrial membrane	1
organelle outer membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGPAT5	GPAT3	Q53EU6	673
AGPAT5	AGPAT1	Q99943	668
AGPAT5	GPAT4	Q86UL3	667
AGPAT5	GPAT2	Q6NUI2	653
AGPAT5	AGPAT2	O15120	641
AGPAT5	LPCAT4	Q643R3	624
AGPAT5	GPAM	Q9HCL2	558
AGPAT5	LPCAT2	Q7L5N7	496
AGPAT5	TAMM41	Q96BW9	464
AGPAT5	SPATA4	Q8NEY3	447
AGPAT5	ZCCHC3	Q9NUD5	434
AGPAT5	LPCAT1	Q8NF37	429
AGPAT5	MBOAT2	Q6ZWT7	426
AGPAT5	TFAP2D	Q7Z6R9	425
AGPAT5	DGAT2	Q96PD7	403

IntAct

81 interactions, top by confidence:

A	B	Type	Score
UBQLN1	AGPAT5	psi-mi:“MI:0915”(physical association)	0.720
AGPAT5	UBQLN1	psi-mi:“MI:0915”(physical association)	0.720
AGPAT5	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
AGPAT5	TMX2	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	AGPAT5	psi-mi:“MI:0915”(physical association)	0.560
	AGPAT5	psi-mi:“MI:0915”(physical association)	0.560
CYB561A3	AGPAT5	psi-mi:“MI:0915”(physical association)	0.560
VDAC1	HK1	psi-mi:“MI:0914”(association)	0.560
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
CDH13	INSIG1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
CD70	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TMCO3	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): AGPAT5 (Two-hybrid), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-RNA), AGPAT5 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Proximity Label-MS), AGPAT5 (Affinity Capture-MS), AGPAT5 (Two-hybrid), CREB3L1 (Two-hybrid)

ESM2 similar proteins: A0A0M4FCN7, A7M6E7, A7M6E8, B4G0F3, B8BKI7, C6JS30, E0CTF3, F4JJJ3, K7K424, K7PEY4, O23617, O48780, O80437, O80738, Q0VCR6, Q0WUI9, Q1LWG4, Q2R483, Q4V9F0, Q5FVP8, Q5XF03, Q5ZJD8, Q6P342, Q6PAZ3, Q70VZ8, Q7L5N7, Q8BYI6, Q8K3K7, Q8L7M0, Q8S8S2, Q94A08, Q94AH8, Q96MH6, Q96PD7, Q9ASU1, Q9C6L5, Q9CAY3, Q9D1E8, Q9D850, Q9DCV3

Diamond homologs: P33333, Q3UN02, Q41745, Q4R581, Q5E9R2, Q5F3X0, Q5R757, Q5RA57, Q6IWY1, Q6NYV8, Q6UWP7, Q8K4X7, Q8L4Y2, Q8LG50, Q924S1, Q9D1E8, Q9D517, Q9LHN4, Q9NRZ5, Q9NRZ7, Q9NUQ2, Q9SYC8, Q9XFW4, Q9US20, O94361, Q20800, Q12185

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AGPAT5	up-regulates	“phosphatidic acid”	“chemical modification”
AGPAT5	“down-regulates quantity”	“1-acyl-sn-glycerol 3-phosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	59
Likely pathogenic	5
Uncertain significance	78
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1339975	GRCh37/hg19 8p23.3-23.1(chr8:158048-11936107)x3	Pathogenic
145525	GRCh38/hg38 8p23.3-23.1(chr8:241530-10191595)x1	Pathogenic
145967	GRCh38/hg38 8p23.3-23.1(chr8:410369-7477103)x1	Pathogenic
146114	GRCh38/hg38 8p23.3-23.1(chr8:241530-7022841)x3	Pathogenic
146718	GRCh38/hg38 8p23.3-21.3(chr8:241530-23198398)x3	Pathogenic
146751	GRCh38/hg38 8p23.3-23.1(chr8:241605-7022824)x1	Pathogenic
147663	GRCh38/hg38 8p23.3-23.1(chr8:241530-7056554)x1	Pathogenic
149174	GRCh38/hg38 8p23.3-23.1(chr8:226452-7981437)x3	Pathogenic
150028	GRCh38/hg38 8p23.2-23.1(chr8:3934205-11526939)x1	Pathogenic
150497	GRCh38/hg38 8p23.3-23.1(chr8:226452-7062751)x1	Pathogenic
150616	GRCh38/hg38 8p23.3-23.1(chr8:226452-7084815)x1	Pathogenic
151132	GRCh38/hg38 8p23.3-23.1(chr8:208048-7141592)x1	Pathogenic
151750	GRCh38/hg38 8p23.3-23.1(chr8:208048-7124466)x1	Pathogenic
154529	GRCh38/hg38 8p23.3-23.1(chr8:241530-10458484)x1	Pathogenic
155181	GRCh38/hg38 8p23.3-23.1(chr8:226452-12698554)x3	Pathogenic
155440	GRCh38/hg38 8p23.3-23.1(chr8:208048-7087252)x1	Pathogenic
155691	GRCh38/hg38 8p23.3-23.1(chr8:208048-7186524)x4	Pathogenic
160883	GRCh38/hg38 8p23.3-23.1(chr8:241530-7022841)x1	Pathogenic
161036	GRCh38/hg38 8p23.3-23.1(chr8:241530-7895064)x3	Pathogenic
161038	GRCh38/hg38 8p23.3-23.1(chr8:241530-7895064)x1	Pathogenic
1703666	GRCh37/hg19 8p23.3-23.1(chr8:158048-10348413)	Pathogenic
1708195	GRCh37/hg19 8p23.3-23.1(chr8:158048-11281408)x1	Pathogenic
1807751	GRCh37/hg19 8p23.3-22(chr8:158049-18936715)x1	Pathogenic
1808721	GRCh37/hg19 8p23.3-23.1(chr8:158049-10965627)x1	Pathogenic
252967	GRCh37/hg19 8p23.3-23.1(chr8:164984-11860845)x3	Pathogenic
253391	GRCh37/hg19 8p23.3-23.1(chr8:190822-6735381)x1	Pathogenic
2580328	GRCh37/hg19 8p23.3-23.1(chr8:10501-11142629)x1	Pathogenic
2671622	Single allele	Pathogenic
2685281	GRCh37/hg19 8p23.3-23.1(chr8:158049-10007143)x1	Pathogenic
2685283	GRCh37/hg19 8p23.3-23.1(chr8:158049-8192683)x1	Pathogenic

SpliceAI

1697 predictions. Top by Δscore:

Variant	Effect	Δscore
8:6732549:T:TA	acceptor_gain	1.0000
8:6732555:T:TA	acceptor_gain	1.0000
8:6732651:G:GG	donor_gain	1.0000
8:6755170:GATAA:G	donor_gain	1.0000
8:6755171:A:G	donor_gain	1.0000
8:6755175:G:GG	donor_gain	1.0000
8:6708883:TCCAG:T	donor_loss	0.9900
8:6708884:CCAG:C	donor_loss	0.9900
8:6708885:CAGG:C	donor_loss	0.9900
8:6708886:AGG:A	donor_loss	0.9900
8:6708888:GTG:G	donor_loss	0.9900
8:6708889:T:A	donor_loss	0.9900
8:6709543:G:GG	donor_gain	0.9900
8:6730709:A:AG	acceptor_gain	0.9900
8:6730710:G:GG	acceptor_gain	0.9900
8:6732544:C:CA	acceptor_gain	0.9900
8:6732553:T:A	acceptor_gain	0.9900
8:6732556:G:A	acceptor_gain	0.9900
8:6732559:A:AG	acceptor_gain	0.9900
8:6732560:G:GG	acceptor_gain	0.9900
8:6732560:GC:G	acceptor_gain	0.9900
8:6732650:AG:A	donor_loss	0.9900
8:6732651:GT:G	donor_loss	0.9900
8:6732652:T:TC	donor_loss	0.9900
8:6732653:A:C	donor_loss	0.9900
8:6741660:GAT:G	acceptor_gain	0.9900
8:6747736:T:G	acceptor_gain	0.9900
8:6755049:A:AG	acceptor_gain	0.9900
8:6755050:G:GG	acceptor_gain	0.9900
8:6755050:GA:G	acceptor_gain	0.9900

AlphaMissense

2377 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:6730716:T:A	W99R	0.999
8:6730716:T:C	W99R	0.999
8:6724927:C:G	H93D	0.998
8:6730738:C:A	A106D	0.997
8:6730768:G:C	R116P	0.997
8:6730780:A:T	K120I	0.997
8:6741676:T:C	F171L	0.997
8:6741678:T:A	F171L	0.997
8:6741678:T:G	F171L	0.997
8:6730718:G:C	W99C	0.996
8:6730718:G:T	W99C	0.996
8:6730810:G:A	G130E	0.996
8:6747724:C:A	A214D	0.996
8:6755158:T:C	F285L	0.996
8:6755160:C:A	F285L	0.996
8:6755160:C:G	F285L	0.996
8:6724927:C:A	H93N	0.995
8:6724929:T:A	H93Q	0.995
8:6724929:T:G	H93Q	0.995
8:6741668:T:C	L168P	0.995
8:6755168:A:T	K288I	0.995
8:6755169:A:C	K288N	0.995
8:6755169:A:T	K288N	0.995
8:6730714:A:T	D98V	0.994
8:6730781:A:C	K120N	0.994
8:6730781:A:T	K120N	0.994
8:6708735:G:C	G23R	0.993
8:6730713:G:C	D98H	0.993
8:6730767:C:A	R116S	0.993
8:6741685:G:C	G174R	0.993

dbSNP variants (sampled 300 via entrez): RS1000042414 (8:6752781 A>C,T), RS1000051761 (8:6723695 G>A,T), RS1000076413 (8:6747672 C>T), RS1000118859 (8:6727763 G>A), RS1000129798 (8:6754189 T>G), RS1000225356 (8:6737634 C>A,G), RS1000226823 (8:6728965 C>T), RS1000228844 (8:6719818 C>T), RS1000262530 (8:6757992 T>C), RS1000267158 (8:6732143 C>T), RS1000271181 (8:6721318 A>G), RS1000290412 (8:6706879 T>C), RS1000379001 (8:6736043 A>G), RS1000391881 (8:6708494 G>T), RS1000439488 (8:6735733 A>G)

Disease associations

OMIM: gene MIM:614796 | disease phenotypes: MIM:143890, MIM:148100, MIM:209850, MIM:187500

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	Limited	Unknown

Mondo (6): hypercholesterolemia, familial, 1 (MONDO:0007750), keloid formation (MONDO:0007847), intellectual disability (MONDO:0001071), autism (MONDO:0005260), tetralogy of fallot (MONDO:0008542), Tourette syndrome (MONDO:0007661)

Orphanet (3): Homozygous familial hypercholesterolemia (Orphanet:391665), Tetralogy of Fallot (Orphanet:3303), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006611_148	HDL cholesterol	9.000000e-10
GCST008078_122	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-09
GCST008078_35	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-08
GCST008079_121	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-11
GCST008079_64	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-09
GCST008086_27	LDL cholesterol levels in current drinkers	2.000000e-07
GCST008086_3	LDL cholesterol levels in current drinkers	4.000000e-07
GCST90011898_112	Alanine aminotransferase levels	8.000000e-09
GCST90011900_206	Serum alkaline phosphatase levels	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066417 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, affects expression, decreases expression	4
Cyclosporine	increases expression	3
bisphenol A	decreases expression, decreases methylation	2
Acetaminophen	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression, decreases reaction	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
obeticholic acid	decreases expression	1
abrine	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Cadmium	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Colforsin	decreases reaction, increases expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Methyl Methanesulfonate	decreases expression	1
Mitoxantrone	affects response to substance	1
Naled	affects expression	1
Nickel	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650860	Binding	Binding affinity to human AGPAT5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
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
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD