PLAAT4

Summary

PLAAT4 (phospholipase A and acyltransferase 4, HGNC:9869) is a protein-coding gene on chromosome 11q12.3, encoding Phospholipase A and acyltransferase 4 (Q9UL19). Exhibits both phospholipase A1/2 and acyltransferase activities.

Retinoids exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1, RARRES2, and RARRES3 are genes whose expression is upregulated by the synthetic retinoid tazarotene. RARRES3 is thought act as a tumor suppressor or growth regulator.

Source: NCBI Gene 5920 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 27 total
• Druggable target: yes
• MANE Select transcript: NM_004585

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9869
Approved symbol	PLAAT4
Name	phospholipase A and acyltransferase 4
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	TIG3, HRASLS4, PLAAT-4, RIG1
Ensembl gene	ENSG00000133321
Ensembl biotype	protein_coding
OMIM	605092
Entrez	5920

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000255688, ENST00000439013, ENST00000537871, ENST00000544107, ENST00000718309, ENST00000870788, ENST00000918724, ENST00000918725, ENST00000918726, ENST00000959278

RefSeq mRNA: 1 — MANE Select: NM_004585 NM_004585

CCDS: CCDS41662

Canonical transcript exons

ENST00000255688 — 4 exons

Exon	Start	End
ENSE00000908980	63539516	63539624
ENSE00002295822	63536808	63536877
ENSE00003474706	63544621	63544889
ENSE00003552581	63546149	63546458

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1845 / max 616.9536, expressed in 1307 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114806	7.9748	1135
114805	7.2097	924

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.10	gold quality
nasal cavity epithelium	UBERON:0005384	98.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.29	gold quality
palpebral conjunctiva	UBERON:0001812	98.26	gold quality
epithelium of bronchus	UBERON:0002031	97.75	gold quality
bronchus	UBERON:0002185	97.69	gold quality
metanephros cortex	UBERON:0010533	97.50	gold quality
bronchial epithelial cell	CL:0002328	97.46	gold quality
upper lobe of left lung	UBERON:0008952	97.36	gold quality
upper lobe of lung	UBERON:0008948	97.29	gold quality
right uterine tube	UBERON:0001302	97.19	gold quality
lymph node	UBERON:0000029	96.67	gold quality
nasal cavity mucosa	UBERON:0001826	96.61	gold quality
right lung	UBERON:0002167	96.47	gold quality
duodenum	UBERON:0002114	96.29	gold quality
gall bladder	UBERON:0002110	96.27	gold quality
leukocyte	CL:0000738	96.21	gold quality
jejunal mucosa	UBERON:0000399	96.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.05	gold quality
mononuclear cell	CL:0000842	95.97	gold quality
monocyte	CL:0000576	95.95	gold quality
adult mammalian kidney	UBERON:0000082	95.93	gold quality
rectum	UBERON:0001052	95.84	gold quality
right lobe of liver	UBERON:0001114	95.78	gold quality
small intestine	UBERON:0002108	95.69	gold quality
lower lobe of lung	UBERON:0008949	95.66	gold quality
trachea	UBERON:0003126	95.35	gold quality
spleen	UBERON:0002106	95.32	gold quality
trigeminal ganglion	UBERON:0001675	94.92	gold quality
blood	UBERON:0000178	94.60	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	111.71
E-HCAD-4	yes	90.74
E-GEOD-125970	yes	63.57
E-CURD-122	yes	58.91
E-MTAB-10553	yes	49.86
E-HCAD-8	yes	39.25
E-MTAB-6701	yes	37.98
E-MTAB-9467	yes	37.44
E-CURD-88	yes	36.58
E-MTAB-10287	yes	33.44
E-HCAD-10	yes	32.90
E-MTAB-8410	yes	30.44
E-GEOD-135922	yes	23.30
E-MTAB-10042	yes	11.90
E-CURD-112	yes	5.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LHX2, PAX2, RARA, RARB

miRNA regulators (miRDB)

13 targeting PLAAT4, 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-6768-5P	99.92	67.36	1942
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-3194-5P	96.80	64.90	1027

Literature-anchored findings (GeneRIF, showing 23)

• induction of TIG3 is associated with the suppression of anchorage-independent growth in certain aerodigestive tract cancer cells (PMID:12879006)
• TIG3 facilitates the terminal stages in keratinocyte differentiation via activation of type I transglutaminase (PMID:12928434)
• altered RARRES3 expression may play a role in the carcinogenesis of the liver and biliary tract. (PMID:15742394)
• identification and characterization of the functional RA response element that is responsible for the RA-mediated induction of RIG1 gene (PMID:15850806)
• TIG3 is negatively regulated by an activated MEK-ERK signaling pathway in ovarian carcinoma. (PMID:15856468)
• The proapoptotic and anti-RAS activities of RIG1 are primarily associated with the Golgi localization of the protein. (PMID:17196792)
• The NC domain, especially the NC motif, plays the major role in RIG1-mediated pro-apoptotic activity. The RIG1(111-123) dodecapeptide exhibited strong pro-apoptotic activity and has potential as an anticancer drug. (PMID:19245694)
• The tumor suppressors TIG3, HRASLS2 and H-rev107 are involved in the phospholipid metabolism with different physiological roles. (PMID:19615464)
• Data suggest that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis. (PMID:21858038)
• We conclude that TG1-catalysed cross-linking, regulated by TIG3, might play an important role in the formation of neuronal tau inclusions in certain tauopathies (PMID:22009441)
• RIG1 gene is a downstream target of p53 in cancer cell lines (PMID:22616991)
• Low RIG1 expression is associated with testis cancer. (PMID:22960220)
• We show that the C-terminal hydrophobic domain targets intact TIG3 to the plasma membrane, but when isolated as an independent element localizes at the mitochondria and a segment of the N-terminal hydrophilic region targets the centrosome. (PMID:24401997)
• These findings argue that TIG3 is involved in the control of keratinocyte differentiation and that loss of TIG3 in transformed cells contributes to the malignant phenotype. (PMID:24599174)
• RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. (PMID:24867881)
• findings provide a new insight into the molecular link between p53, protein acylation and Wnt/beta-catenin signaling whereby RARRES3 plays a pivotal role in modulating the acylation status of signaling proteins. (PMID:25361079)
• the flexible main loop of H-REV107, but not that of TIG3, is critical for its NTD to modulate its CTD in inducing cell death. (PMID:25871522)
• Letter: Interleukin-22 inhibits tazarotene-induced gene 3 expression in keratinocytes via MAPK-ERK1/2 and JAK2/STAT3 signaling. (PMID:26464031)
• Overexpression of TIG3 suppresses tumor growth in hepatocellular carcinoma (PMID:26951515)
• Identified the tumor suppressor RARRES3 as a critical target of G9a. Epigenetic silencing of RARRES3 contributed to the tumor-promoting function of G9a (PMID:28532996)
• this study indicated that increased expression of TIG3 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients. We then hypothesize that TIG3 may function in a different pattern in glioblastoma (PMID:28639915)
• we observed frameshift mutations of RARRES3 in 11 cases of colorectal cancer (PMID:29496306)
• Overexpression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of Toxoplasma gondii infection. (PMID:34871166)

Cross-species orthologs

0 orthologs

Paralogs (7): LRAT (ENSG00000121207), PLAAT1 (ENSG00000127252), PLAAT2 (ENSG00000133328), LRATD1 (ENSG00000162981), PLAAT5 (ENSG00000168004), LRATD2 (ENSG00000168672), PLAAT3 (ENSG00000176485)

Protein

Protein identifiers

Phospholipase A and acyltransferase 4 — Q9UL19 (reviewed: Q9UL19)

Alternative names: HRAS-like suppressor 4, RAR-responsive protein TIG3, Retinoic acid receptor responder protein 3, Retinoid-inducible gene 1 protein, Tazarotene-induced gene 3 protein

All UniProt accessions (1): Q9UL19

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits both phospholipase A1/2 and acyltransferase activities. Shows phospholipase A1 (PLA1) and A2 (PLA2), catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids. For most substrates, PLA1 activity is much higher than PLA2 activity. Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid. Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs).

Subcellular location. Membrane.

Tissue specificity. Widely expressed.

Induction. By all-trans-retinoic acid and synthetic retinoids.

Similarity. Belongs to the H-rev107 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UL19-1	1	yes
Q9UL19-2	2

RefSeq proteins (1): NP_004576* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007053	LRAT_dom	Domain
IPR051496	H-rev107_PLA/AT	Family

Pfam: PF04970

Catalyzed reactions (Rhea), 12 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:15801)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:18689)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:38779)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:38783)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 2-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:40487)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:40571)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z,12Z)-octadecadienoate + H(+) (RHEA:40815)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41223)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphoethanolamine + hexadecanoate + H(+) (RHEA:41348)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = 2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphoethanolamine + hexadecanoate + H(+) (RHEA:45164)
• 1-hexanoyl-2-acyl-sn-glycero-3-phosphocholine + H2O = hexanoate + a 2-acyl-sn-glycero-3-phosphocholine + H(+) (RHEA:53496)
• 1,2-diheptadecanoyl-sn-glycero-3-phosphoethanolamine + 1-(9Z-octadecenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine = 1,2-diheptadecanoyl-sn-glycero-3-phospho-N-hexadecanoyl-ethanolamine + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H(+) (RHEA:53524)

UniProt features (29 total): strand 8, helix 5, sequence conflict 3, active site 3, topological domain 2, sequence variant 2, turn 2, chain 1, transmembrane region 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7ZOT	X-RAY DIFFRACTION	1.74
9KFL	X-RAY DIFFRACTION	3.45
2LKT	SOLUTION NMR
2MY9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL19-F1	77.02	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.

Catalytic / active sites (3): 23; 35; 113 (acyl-thioester intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1482839	Acyl chain remodelling of PE

MSigDB gene sets: 262 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, JI_RESPONSE_TO_FSH_UP, MODULE_255, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, BROWNE_HCMV_INFECTION_8HR_UP, MODULE_45, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, WIELAND_UP_BY_HBV_INFECTION

GO Biological Process (8): phospholipid metabolic process (GO:0006644), negative regulation of cell population proliferation (GO:0008285), lipid catabolic process (GO:0016042), phosphatidylethanolamine acyl-chain remodeling (GO:0036152), positive regulation of keratinocyte differentiation (GO:0045618), N-acylphosphatidylethanolamine metabolic process (GO:0070292), positive regulation of protein-glutamine gamma-glutamyltransferase activity (GO:0150074), lipid metabolic process (GO:0006629)

GO Molecular Function (7): A2-type glycerophospholipase activity (GO:0004623), glycerophospholipid phospholipase A1 activity (GO:0008970), obsolete N-acyltransferase activity (GO:0016410), acyltransferase activity (GO:0016746), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), 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
cellular anatomical structure	3
lipid metabolic process	2
catalytic activity	2
organophosphate metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
catabolic process	1
phosphatidylcholine metabolic process	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	1
phosphatidylethanolamine metabolic process	1
protein-glutamine gamma-glutamyltransferase activity	1
positive regulation of catalytic activity	1
regulation of transferase activity	1
primary metabolic process	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
A1-type glycerophospholipase activity	1
transferase activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

3146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAAT4	CRABP2	P29373	752
PLAAT4	RARG	P13631	692
PLAAT4	RARB	P10826	608
PLAAT4	TCHP	Q9BT92	489
PLAAT4	RARA	P10276	474
PLAAT4	APOL6	Q9BWW8	461
PLAAT4	RXRA	P19793	434
PLAAT4	TGM2	P21980	431
PLAAT4	RARRES1	P49788	415
PLAAT4	PASD1	Q8IV76	406
PLAAT4	OSBPL6	Q9BZF3	400
PLAAT4	MS4A12	Q9NXJ0	398
PLAAT4	SCGB1D2	O95969	396
PLAAT4	SRC	P12931	389
PLAAT4	MUC13	Q9H3R2	389

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PLAAT4	SGTA	psi-mi:“MI:0915”(physical association)	0.670
SGTA	PLAAT4	psi-mi:“MI:0915”(physical association)	0.670
PIK3R3	PLAAT4	psi-mi:“MI:0915”(physical association)	0.560
PLAAT4	CASTOR1	psi-mi:“MI:0915”(physical association)	0.400
PLAAT4	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PIK3R3	PLAAT4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): SGTA (Two-hybrid), RARRES3 (Biochemical Activity), SDC4 (Two-hybrid), RARRES3 (Affinity Capture-Western), SDC4 (Affinity Capture-Western), RARRES3 (Affinity Capture-Western), RNF123 (Affinity Capture-Western), RARRES3 (Affinity Capture-Western), MAVS (Affinity Capture-Western), RNF135 (Affinity Capture-Western), RARRES3 (Affinity Capture-Western), RARRES3 (Two-hybrid), WWOX (Affinity Capture-MS), C18orf8 (Affinity Capture-MS), SLC5A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IMY7, A0A0R4IY06, A0JPF9, A2AP18, A5PJN5, C0IN03, D2KX21, E1BVR9, E9PYK3, F1ND48, O00534, O75038, O94952, O95237, P0C1Q3, P53817, Q1LWG4, Q1LZ50, Q32PY6, Q4R3W5, Q4R6L3, Q5M7X9, Q5R5S1, Q5RJG7, Q5S6T3, Q5T8I9, Q6DC39, Q75WE7, Q7Z5M8, Q7ZU92, Q8BYI6, Q8C0L6, Q8CAE2, Q8CAS9, Q8K3R3, Q8NHH9, Q8SPR7, Q8VDH1, Q90678, Q93V51

Diamond homologs: A0A0R4IY06, D2KX21, P53816, P53817, Q4KLN5, Q5R611, Q8R3U1, Q96KN8, Q9BGL2, Q9CPX5, Q9HDD0, Q9JI61, Q9NWW9, Q9QZU4, Q9UL19, O95237, Q9JI60, Q96KN1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

486 predictions. Top by Δscore:

Variant	Effect	Δscore
11:63536877:GGTA:G	donor_loss	1.0000
11:63536878:G:GG	donor_gain	1.0000
11:63536879:T:A	donor_loss	1.0000
11:63539625:G:GG	donor_gain	1.0000
11:63536873:CTTCG:C	donor_gain	0.9900
11:63536876:CG:C	donor_gain	0.9900
11:63536877:GG:G	donor_gain	0.9900
11:63539630:G:GT	donor_gain	0.9900
11:63544887:CAGGT:C	donor_loss	0.9900
11:63544888:AGGTA:A	donor_loss	0.9900
11:63544890:GT:G	donor_loss	0.9900
11:63544891:T:A	donor_loss	0.9900
11:63546143:TTGCA:T	acceptor_loss	0.9900
11:63546144:TGCA:T	acceptor_loss	0.9900
11:63546145:GCAG:G	acceptor_loss	0.9900
11:63546146:CAGG:C	acceptor_loss	0.9900
11:63546147:A:T	acceptor_loss	0.9900
11:63546148:G:GC	acceptor_loss	0.9900
11:63536874:TTCG:T	donor_gain	0.9800
11:63536875:TCG:T	donor_gain	0.9800
11:63539622:CAAG:C	donor_loss	0.9800
11:63539624:AG:A	donor_loss	0.9800
11:63539625:GTAAG:G	donor_loss	0.9800
11:63539626:TAA:T	donor_loss	0.9800
11:63539627:A:AG	donor_loss	0.9800
11:63544620:GGTGA:G	acceptor_gain	0.9800
11:63544890:G:GG	donor_gain	0.9800
11:63546147:A:AG	acceptor_gain	0.9700
11:63546147:AGGT:A	acceptor_gain	0.9700
11:63546148:G:GG	acceptor_gain	0.9700

AlphaMissense

1063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:63544865:A:C	R121S	0.994
11:63544865:A:T	R121S	0.994
11:63544848:T:C	F116L	0.991
11:63544850:T:A	F116L	0.991
11:63544850:T:G	F116L	0.991
11:63544864:G:C	R121T	0.991
11:63544818:T:C	Y106H	0.989
11:63539575:C:A	H23Q	0.988
11:63539575:C:G	H23Q	0.988
11:63539578:G:C	W24C	0.988
11:63539578:G:T	W24C	0.988
11:63544840:G:A	C113Y	0.986
11:63544849:T:C	F116S	0.986
11:63539544:T:C	L13P	0.984
11:63544849:T:G	F116C	0.983
11:63544863:A:G	R121G	0.983
11:63539611:T:A	H35Q	0.982
11:63539611:T:G	H35Q	0.982
11:63539538:G:A	G11E	0.981
11:63539576:T:A	W24R	0.981
11:63539576:T:C	W24R	0.981
11:63544788:G:C	A96P	0.981
11:63544844:G:C	E114D	0.981
11:63544844:G:T	E114D	0.981
11:63544841:T:G	C113W	0.980
11:63544819:A:G	Y106C	0.979
11:63544819:A:C	Y106S	0.978
11:63544837:A:T	N112I	0.978
11:63539538:G:T	G11V	0.977
11:63539553:T:C	I16T	0.977

dbSNP variants (sampled 300 via entrez): RS1000127828 (11:63536331 C>T), RS1000132274 (11:63541093 A>C,G), RS1000160666 (11:63536521 T>C), RS1000341352 (11:63544396 C>A,T), RS1000466034 (11:63537634 C>T), RS1000497233 (11:63538007 C>T), RS1000808463 (11:63546445 C>T), RS1001078321 (11:63545813 G>A), RS1001648932 (11:63537207 G>A), RS1001797099 (11:63545391 C>T), RS1001953044 (11:63538378 G>A,C), RS1002015927 (11:63536888 C>A), RS1002129486 (11:63546574 G>T), RS1002236067 (11:63538944 C>A,T), RS1002239996 (11:63545904 C>T)

Disease associations

OMIM: gene MIM:605092 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630864 (SINGLE PROTEIN)

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

ChEMBL bioactivities

35 potent at pChembl≥5 of 35 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50.12	nM	CHEMBL4643782
7.10	IC50	79.43	nM	CHEMBL4649677
6.70	IC50	199.5	nM	CHEMBL4639478
6.70	IC50	199.5	nM	CHEMBL4636806
6.20	IC50	631	nM	CHEMBL4645342
6.20	IC50	631	nM	CHEMBL4644464
6.20	IC50	631	nM	CHEMBL4639199
6.10	IC50	794.3	nM	CHEMBL4643099
6.00	IC50	1000	nM	CHEMBL4633449
6.00	IC50	1000	nM	CHEMBL4641977
5.90	IC50	1259	nM	CHEMBL4643675
5.90	IC50	1259	nM	CHEMBL4641818
5.90	IC50	1259	nM	CHEMBL4648272
5.90	IC50	1259	nM	CHEMBL4632512
5.90	IC50	1259	nM	CHEMBL4639242
5.90	IC50	1259	nM	CHEMBL4644324
5.80	IC50	1585	nM	CHEMBL4636463
5.80	IC50	1585	nM	CHEMBL4640863
5.80	IC50	1585	nM	CHEMBL4640676
5.80	IC50	1585	nM	CHEMBL4636379
5.60	IC50	2512	nM	CHEMBL4646350
5.60	IC50	2512	nM	CHEMBL4649884
5.60	IC50	2512	nM	CHEMBL4639235
5.60	IC50	2512	nM	CHEMBL4645552
5.60	IC50	2512	nM	CHEMBL4646429
5.60	IC50	2512	nM	CHEMBL4636282
5.60	IC50	2512	nM	CHEMBL4645578
5.60	IC50	2512	nM	CHEMBL4642795
5.50	IC50	3162	nM	CHEMBL4649801
5.40	IC50	3981	nM	CHEMBL4638043
5.20	IC50	6310	nM	CHEMBL4636625
5.20	IC50	6310	nM	CHEMBL4643908
5.10	IC50	7943	nM	CHEMBL4640894
5.00	IC50	1e+04	nM	CHEMBL4641304
5.00	IC50	1e+04	nM	CHEMBL4634598

PubChem BioAssay actives

35 with measured affinity, of 58 total; 35 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-oxo-N-[2-(4-phenoxyphenyl)ethyl]-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.0501	uM
2-oxo-5-phenyl-N-[2-[4-[[6-(trifluoromethyl)-3-pyridinyl]oxy]phenyl]ethyl]pentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.0794	uM
N-[2-[4-(2-chloropyrimidin-4-yl)oxyphenyl]ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.1995	uM
N-[2-(4-bromophenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.1995	uM
2-oxo-5-phenyl-N-[2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]ethyl]pentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.6310	uM
2-oxo-5-phenyl-N-[2-(4-pyrazin-2-yloxyphenyl)ethyl]pentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.6310	uM
2-oxo-5-phenyl-N-(2-phenylethyl)pentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.6310	uM
N-[2-(2,4-dichlorophenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	0.7943	uM
4-(3,4-dichlorophenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.0000	uM
N-[2-(3-chlorophenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.0000	uM
4-(3-chlorophenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.2589	uM
N-[2-(4-methylphenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.2589	uM
4-(4-methoxyphenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.2589	uM
4-(4-chlorophenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.2589	uM
2-oxo-5-phenyl-N-[2-(4-pyrimidin-2-yloxyphenyl)ethyl]pentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.2589	uM
2-oxo-4-(4-phenoxyphenyl)-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.2589	uM
4-(4-chlorophenyl)-2-oxo-N-(4-phenylbutyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.5849	uM
N-[2-(4-methoxyphenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.5849	uM
2-oxo-6-phenyl-N-(2-phenylethyl)hexanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.5849	uM
4-(4-methylphenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	1.5849	uM
4-(2-chlorophenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
(E)-2-oxo-N-(2-phenylethyl)-4-(3-phenylphenyl)but-3-enamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
N-[2-(2-chlorophenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
N-[2-(4-hydroxyphenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
N-benzyl-4-(4-chlorophenyl)-2-oxobutanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
(E)-4-(4-methoxyphenyl)-2-oxo-N-(2-phenylethyl)but-3-enamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
(E)-4-(4-chlorophenyl)-2-oxo-N-(2-phenylethyl)but-3-enamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
2-oxo-N-(2-phenylethyl)-4-[4-(trifluoromethyl)phenyl]butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	2.5119	uM
2-oxo-4-phenyl-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	3.1623	uM
4-(4-chlorophenyl)-N-ethyl-2-oxobutanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	3.9811	uM
(E)-4-(4-bromophenyl)-2-oxo-N-(2-phenylethyl)but-3-enamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	6.3096	uM
N-[2-(3,4-dimethoxyphenyl)ethyl]-2-oxo-5-phenylpentanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	6.3096	uM
(E)-4-(3-bromophenyl)-2-oxo-N-(2-phenylethyl)but-3-enamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	7.9433	uM
(E)-2-oxo-4-phenyl-N-(2-phenylethyl)but-3-enamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	10.0000	uM
4-(4-fluorophenyl)-2-oxo-N-(2-phenylethyl)butanamide	1666053: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	5
Tretinoin	increases expression	5
sodium arsenite	decreases expression, increases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance	2
Asbestos, Serpentine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, affects cotreatment	2
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, increases expression	1
4-oxoretinoic acid	increases expression	1
apocarotenal	decreases expression	1
lead acetate	affects cotreatment, decreases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1
1-nitropyrene	decreases expression	1
4-oxoretinol	increases expression	1
tamibarotene	increases expression	1
ICG 001	increases expression	1
jinfukang	increases expression, affects cotreatment	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4626914	Binding	Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis	Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1GY	Abcam A-549 PLAAT4 KO 1	Cancer cell line	Male
CVCL_B2PH	Abcam A-549 PLAAT4 KO 2	Cancer cell line	Male
CVCL_E4U7	KOLF2.1J PLAAT4 9.8kbdel DEL/DEL	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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