PLAAT1

Summary

PLAAT1 (phospholipase A and acyltransferase 1, HGNC:14922) is a protein-coding gene on chromosome 3q29, encoding Phospholipase A and acyltransferase 1 (Q9HDD0). Exhibits both phospholipase A1/2 and acyltransferase activities.

Enables acyltransferase activity, transferring groups other than amino-acyl groups and phospholipase activity. Involved in N-acylphosphatidylethanolamine metabolic process and phosphatidylcholine metabolic process. Located in cytoplasm and nucleus.

Source: NCBI Gene 57110 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_020386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14922
Approved symbol	PLAAT1
Name	phospholipase A and acyltransferase 1
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	H-REV107, HRASLS1, A-C1, PLA/AT1, PLAAT-1
Ensembl gene	ENSG00000127252
Ensembl biotype	protein_coding
OMIM	606487
Entrez	57110

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 21 protein_coding, 1 nonsense_mediated_decay

ENST00000264735, ENST00000416012, ENST00000650797, ENST00000853270, ENST00000853271, ENST00000853272, ENST00000853273, ENST00000853274, ENST00000853275, ENST00000853276, ENST00000853277, ENST00000853278, ENST00000916957, ENST00000916958, ENST00000916959, ENST00000916960, ENST00000916961, ENST00000916962, ENST00000971779, ENST00000971780, ENST00000971781, ENST00000971782

RefSeq mRNA: 2 — MANE Select: NM_020386 NM_001366112, NM_020386

CCDS: CCDS3303

Canonical transcript exons

ENST00000264735 — 4 exons

Exon	Start	End
ENSE00000871509	193270604	193270855
ENSE00000871510	193262970	193263235
ENSE00000871511	193255651	193255789
ENSE00003662733	193241222	193241533

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 98.97.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5642 / max 296.6984, expressed in 662 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40609	2.1040	628
40610	0.1905	77
40611	0.1354	43
40608	0.0896	29
40606	0.0333	7
40607	0.0114	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.97	gold quality
male germ cell	CL:0000015	97.47	gold quality
left testis	UBERON:0004533	96.22	gold quality
right testis	UBERON:0004534	95.76	gold quality
adult organism	UBERON:0007023	95.14	gold quality
testis	UBERON:0000473	94.49	gold quality
endothelial cell	CL:0000115	94.16	gold quality
vastus lateralis	UBERON:0001379	93.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.81	gold quality
biceps brachii	UBERON:0001507	92.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.83	gold quality
quadriceps femoris	UBERON:0001377	92.75	gold quality
skeletal muscle tissue	UBERON:0001134	91.59	gold quality
gastrocnemius	UBERON:0001388	91.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.11	gold quality
muscle organ	UBERON:0001630	91.07	gold quality
muscle of leg	UBERON:0001383	90.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.96	gold quality
deltoid	UBERON:0001476	87.81	gold quality
esophagus squamous epithelium	UBERON:0006920	87.64	gold quality
triceps brachii	UBERON:0001509	87.43	gold quality
secondary oocyte	CL:0000655	86.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.86	gold quality
muscle tissue	UBERON:0002385	86.75	gold quality
gluteal muscle	UBERON:0002000	85.25	gold quality
middle temporal gyrus	UBERON:0002771	84.98	gold quality
diaphragm	UBERON:0001103	84.41	gold quality
epithelium of esophagus	UBERON:0001976	83.98	gold quality
tibia	UBERON:0000979	83.45	gold quality
oocyte	CL:0000023	82.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	28.04
E-ANND-3	no	2.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, SP1, SP3

Literature-anchored findings (GeneRIF, showing 5)

• The phospholipase active site possesses a structurally conserved Cys-His-His triad as found in NlpC/P60 peptidases, indicating H-REV107 should adopt a similar catalytic mechanism towards phospholipid substrates to that of NlpC/P60 peptidases. (PMID:20837014)
• a possible enzyme activity of A-C1 (PMID:21880860)
• The HRASLS (PLA/AT) subfamily of enzymes. (PMID:26503625)
• A novel molecular mechanism describing K-Ras and H-REV107 binding is suggested and insights into new K-Ras effector target drugs are provided. (PMID:28743497)
• Effects of Lipid Metabolism-Related Genes PTGIS and HRASLS on Phenotype, Prognosis, and Tumor Immunity in Lung Squamous Cell Carcinoma. (PMID:36703911)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plaat1l	ENSDARG00000074014
danio_rerio	plaat1	ENSDARG00000100021
mus_musculus	Plaat1	ENSMUSG00000022525
rattus_norvegicus	Plaat1	ENSRNOG00000001711

Paralogs (7): LRAT (ENSG00000121207), PLAAT4 (ENSG00000133321), PLAAT2 (ENSG00000133328), LRATD1 (ENSG00000162981), PLAAT5 (ENSG00000168004), LRATD2 (ENSG00000168672), PLAAT3 (ENSG00000176485)

Protein

Protein identifiers

Phospholipase A and acyltransferase 1 — Q9HDD0 (reviewed: Q9HDD0)

Alternative names: HRAS-like suppressor 1, Phospholipid-metabolizing enzyme A-C1

All UniProt accessions (2): Q9HDD0, H7C3Y1

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits both phospholipase A1/2 and acyltransferase activities. Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids. 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. Cytoplasm Nucleus. Cytoplasm.

Tissue specificity. Abundantly expressed in testis, skeletal muscle, brain, and heart. Highly expressed in the testis, skeletal muscle, brain, heart, and thyroid.

Similarity. Belongs to the H-rev107 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HDD0-1	1, PLAAT-1S	yes
Q9HDD0-2	2, PLAAT-1L

RefSeq proteins (2): NP_001353041, NP_065119* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF04970

Catalyzed reactions (Rhea), 8 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-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40431)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 2-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:40487)
• 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)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine = hexadecanoyl-sn-glycero-3-phosphocholine + N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H(+) (RHEA:41360)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + a 2-acyl-sn-glycero-3-phosphocholine = a 1-hexadecanoyl-2-acyl-sn-glycero-3-phosphocholine + 2-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:41364)

UniProt features (10 total): topological domain 2, active site 2, sequence conflict 2, chain 1, transmembrane region 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HDD0-F1	72.65	0.45

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 (2): 30; 119 (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: 118 (showing top): GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, FINAK_BREAST_CANCER_SDPP_SIGNATURE, GOBP_AMIDE_METABOLIC_PROCESS, GNF2_CCNA1, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_LIPID_METABOLIC_PROCESS, VANTVEER_BREAST_CANCER_POOR_PROGNOSIS, GOBP_SENSORY_ORGAN_DEVELOPMENT, HAN_SATB1_TARGETS_DN

GO Biological Process (6): lipid catabolic process (GO:0016042), phosphatidylcholine metabolic process (GO:0046470), N-acylphosphatidylethanolamine metabolic process (GO:0070292), lens fiber cell differentiation (GO:0070306), organelle disassembly (GO:1903008), lipid metabolic process (GO:0006629)

GO Molecular Function (8): A2-type glycerophospholipase activity (GO:0004623), obsolete O-acyltransferase activity (GO:0008374), glycerophospholipid phospholipase A1 activity (GO:0008970), obsolete N-acyltransferase activity (GO:0016410), glycerophospholipase activity (GO:0004620), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleus (GO:0005634), nuclear envelope lumen (GO:0005641), cytoplasm (GO:0005737), mitochondrion (GO:0005739), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), 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
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
cytoplasm	3
catalytic activity	2
lipid metabolic process	1
catabolic process	1
glycerophospholipid metabolic process	1
phosphatidylethanolamine metabolic process	1
lens development in camera-type eye	1
epithelial cell differentiation	1
organelle organization	1
cellular component disassembly	1
primary metabolic process	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
A1-type glycerophospholipase activity	1
phospholipase activity	1
binding	1
nuclear envelope	1
organelle envelope lumen	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1

Protein interactions and networks

STRING

2806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAAT1	CRABP2	P29373	717
PLAAT1	RARG	P13631	635
PLAAT1	LRATD2	Q96KN1	595
PLAAT1	RARB	P10826	591
PLAAT1	HRAS	P01112	574
PLAAT1	KRAS	P01116	500
PLAAT1	THBD	P07204	498
PLAAT1	TCHP	Q9BT92	460
PLAAT1	LRATD1	Q96KN4	455
PLAAT1	RTN4RL1	Q86UN2	455
PLAAT1	RDH12	Q96NR8	452
PLAAT1	LIPH	Q8WWY8	446
PLAAT1	ARPC1B	O15143	446
PLAAT1	CHAC2	Q8WUX2	441
PLAAT1	FLNC	Q14315	440

IntAct

23 interactions, top by confidence:

A	B	Type	Score
POU6F2	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
HGS	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
TLX3	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
PLAAT1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
ZIC1	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
DNAAF19	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
PLAAT1	HIDE1	psi-mi:“MI:0914”(association)	0.350
PLAAT1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.000
ZIC1	PLAAT1	psi-mi:“MI:0915”(physical association)	0.000
GPANK1	PLAAT1	psi-mi:“MI:0915”(physical association)	0.000
DNAAF19	PLAAT1	psi-mi:“MI:0915”(physical association)	0.000

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1405 predictions. Top by Δscore:

Variant	Effect	Δscore
3:193241529:G:GG	donor_gain	1.0000
3:193262966:ATAGA:A	acceptor_loss	1.0000
3:193262967:TA:T	acceptor_loss	1.0000
3:193262968:A:AG	acceptor_gain	1.0000
3:193262968:AGA:A	acceptor_loss	1.0000
3:193262968:AGAT:A	acceptor_gain	1.0000
3:193262969:G:GG	acceptor_gain	1.0000
3:193262969:GAT:G	acceptor_gain	1.0000
3:193262969:GATG:G	acceptor_gain	1.0000
3:193276831:C:CC	acceptor_gain	1.0000
3:193241527:GA:G	donor_gain	0.9900
3:193255760:A:AG	donor_gain	0.9900
3:193263232:GCAG:G	donor_gain	0.9900
3:193263234:AGGTA:A	donor_loss	0.9900
3:193263237:T:A	donor_loss	0.9900
3:193276788:C:CT	donor_gain	0.9900
3:193276827:TCAA:T	acceptor_gain	0.9900
3:193276828:CAA:C	acceptor_gain	0.9900
3:193276828:CAAC:C	acceptor_gain	0.9900
3:193244737:ACAG:A	donor_gain	0.9800
3:193262969:GA:G	acceptor_gain	0.9800
3:193263236:G:GG	donor_gain	0.9800
3:193270602:A:AG	acceptor_gain	0.9800
3:193270603:G:GG	acceptor_gain	0.9800
3:193275301:TC:T	acceptor_gain	0.9800
3:193275302:CC:C	acceptor_gain	0.9800
3:193255637:ATTT:A	acceptor_loss	0.9700
3:193255638:T:G	acceptor_loss	0.9700
3:193255640:T:TA	acceptor_loss	0.9700
3:193255644:ATTGC:A	acceptor_loss	0.9700

AlphaMissense

1095 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:193263209:C:A	R127S	0.977
3:193263210:G:C	R127P	0.963
3:193263042:T:C	L71S	0.952
3:193255769:T:A	V40D	0.948
3:193255744:G:C	A32P	0.941
3:193263194:T:C	F122L	0.938
3:193263196:T:A	F122L	0.938
3:193263196:T:G	F122L	0.938
3:193255743:G:C	W31C	0.937
3:193255743:G:T	W31C	0.937
3:193263190:A:C	E120D	0.932
3:193263190:A:T	E120D	0.932
3:193263207:T:C	L126P	0.929
3:193263209:C:G	R127G	0.929
3:193255716:A:C	E22D	0.927
3:193255716:A:T	E22D	0.927
3:193255741:T:A	W31R	0.926
3:193255741:T:C	W31R	0.926
3:193255709:T:C	L20S	0.925
3:193255712:T:A	I21N	0.924
3:193263027:T:A	V66E	0.918
3:193263189:A:T	E120V	0.915
3:193255776:C:A	N42K	0.914
3:193255776:C:G	N42K	0.914
3:193263235:G:C	Q135H	0.910
3:193263235:G:T	Q135H	0.910
3:193263184:C:A	N118K	0.903
3:193263184:C:G	N118K	0.903
3:193263195:T:C	F122S	0.902
3:193255702:G:T	G18W	0.899

dbSNP variants (sampled 300 via entrez): RS1000070347 (3:193254468 A>T), RS1000096110 (3:193277584 C>A,G), RS1000185179 (3:193272561 G>A), RS1000219075 (3:193269786 A>G), RS1000245884 (3:193239286 A>G,T), RS1000334706 (3:193259158 T>C), RS1000418323 (3:193265827 C>A), RS1000491448 (3:193272921 C>A), RS1000503403 (3:193244185 C>G), RS1000504080 (3:193254196 G>A), RS1000553871 (3:193254206 C>T), RS1000635539 (3:193239011 T>G), RS1000691263 (3:193253919 T>C), RS1000693551 (3:193279407 T>A,G), RS1000701970 (3:193279154 A>G,T)

Disease associations

OMIM: gene MIM:606487 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_128	Metabolite levels	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010355	diacylglycerol 36:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
Vorinostat	affects cotreatment, increases expression	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
decabromobiphenyl ether	affects expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	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	decreases expression	1
Temozolomide	decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	increases expression	1
Silicon Dioxide	increases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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