PAFAH2

Summary

PAFAH2 (platelet activating factor acetylhydrolase 2, HGNC:8579) is a protein-coding gene on chromosome 1p36.11, encoding Platelet-activating factor acetylhydrolase 2, cytoplasmic (Q99487). Catalyzes the hydrolyze of the acetyl group at the sn-2 position of platelet-activating factor (PAF) and its analogs, leading to their inactivation.

This gene encodes platelet-activating factor acetylhydrolase isoform 2, a single-subunit intracellular enzyme that catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). However, this lipase exhibits a broader substrate specificity than simply platelet activating factor. Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist, and both are multi-subunit enzymes. Additionally, there is a single-subunit serum isoform of this enzyme.

Source: NCBI Gene 5051 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 90 total — 1 pathogenic
• MANE Select transcript: NM_000437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8579
Approved symbol	PAFAH2
Name	platelet activating factor acetylhydrolase 2
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	HSD-PLA2
Ensembl gene	ENSG00000158006
Ensembl biotype	protein_coding
OMIM	602344
Entrez	5051

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000374282, ENST00000374284, ENST00000439092, ENST00000441420, ENST00000464540, ENST00000476611, ENST00000493892, ENST00000872702, ENST00000872703, ENST00000872704, ENST00000872705, ENST00000872706, ENST00000872707, ENST00000872708, ENST00000872709, ENST00000872710, ENST00000931127, ENST00000931128, ENST00000942550, ENST00000942551

RefSeq mRNA: 1 — MANE Select: NM_000437 NM_000437

CCDS: CCDS270

Canonical transcript exons

ENST00000374282 — 11 exons

Exon	Start	End
ENSE00001036467	25988231	25988327
ENSE00001036474	25989448	25989601
ENSE00001036475	25976682	25976773
ENSE00001036476	25972558	25972712
ENSE00001036478	25974480	25974650
ENSE00001208903	25998025	25998063
ENSE00001463009	25959767	25962083
ENSE00003524697	25983946	25984087
ENSE00003546004	25990727	25990863
ENSE00003558677	25984460	25984528
ENSE00003604365	25982364	25982477

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 92.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2907 / max 130.4002, expressed in 1671 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11132	3.9903	1622
11128	0.8244	127
201415	0.3272	155
11129	0.0942	33
11131	0.0547	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	92.15	gold quality
colonic epithelium	UBERON:0000397	91.69	gold quality
pancreas	UBERON:0001264	88.65	gold quality
granulocyte	CL:0000094	87.95	gold quality
adrenal tissue	UBERON:0018303	87.39	gold quality
islet of Langerhans	UBERON:0000006	86.74	gold quality
rectum	UBERON:0001052	86.20	gold quality
thymus	UBERON:0002370	85.89	gold quality
mucosa of transverse colon	UBERON:0004991	85.86	gold quality
gastrocnemius	UBERON:0001388	85.55	gold quality
muscle of leg	UBERON:0001383	84.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.81	gold quality
type B pancreatic cell	CL:0000169	82.80	gold quality
olfactory bulb	UBERON:0002264	82.51	gold quality
gall bladder	UBERON:0002110	82.39	gold quality
buccal mucosa cell	CL:0002336	82.18	silver quality
stromal cell of endometrium	CL:0002255	81.88	gold quality
transverse colon	UBERON:0001157	80.97	gold quality
bone marrow cell	CL:0002092	80.93	gold quality
right lobe of liver	UBERON:0001114	80.76	gold quality
muscle organ	UBERON:0001630	80.73	gold quality
duodenum	UBERON:0002114	80.63	gold quality
adult mammalian kidney	UBERON:0000082	80.55	gold quality
right adrenal gland cortex	UBERON:0035827	80.14	gold quality
body of stomach	UBERON:0001161	80.08	gold quality
small intestine	UBERON:0002108	79.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.88	gold quality
secondary oocyte	CL:0000655	79.86	gold quality
smooth muscle tissue	UBERON:0001135	79.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting PAFAH2, 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-4425	100.00	67.59	1049
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-12124	99.68	69.17	2700

Literature-anchored findings (GeneRIF, showing 6)

• examines substrate specificity for intracellular and plasma PAF-AHs (PMID:11294621)
• presence of platelet-activating factor acetylhydrolase II in a restricted pattern in human skin; it is involved in protecting this organ against oxidative stress through the degradation of oxidatively modified bioactive phospholipids. (PMID:12406338)
• Lp-PLA2 was higher in those with more extensive Coronary artery disease (PMID:17157859)
• PAF-AH II exerts strong neuroprotective effects against ischemic injury: the neurological deficit scores, cerebral edema index, and relative infarction volume are all significantly lower in PAFAH2 transgenic mice than in wild-type mice. (PMID:17272759)
• The oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. (PMID:25707358)
• Data show that the activity of plasma platelet activating factor acetylhydrolase (PAF-AH) increases in parallel with diabetic retinopathy (DR) severity. (PMID:26791393)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pafah2	ENSMUSG00000037366
rattus_norvegicus	Pafah2	ENSRNOG00000022288
caenorhabditis_elegans	paf-1	WBGENE00003906
caenorhabditis_elegans		WBGENE00003907

Paralogs (1): PLA2G7 (ENSG00000146070)

Protein

Protein identifiers

Platelet-activating factor acetylhydrolase 2, cytoplasmic — Q99487 (reviewed: Q99487)

Alternative names: PAF:lysophospholipid transacetylase, PAF:sphingosine transacetylase, Platelet-activating factor acetyltransferase PAFAH2, Serine-dependent phospholipase A2

All UniProt accessions (3): Q99487, Q5SY00, Q5SY01

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolyze of the acetyl group at the sn-2 position of platelet-activating factor (PAF) and its analogs, leading to their inactivation. Hydrolyzes propionyl and butyroyl moieties approximately half as effectively as PAF. Also catalyzes transacetylation of the acetyl group from platelet-activating factor (PAF) to lysoplasmalogen and to sphingosine, producing plasmalogen analogs of PAF and N-acetylsphingosine (C2-ceramide) respectively. Has a marked selectivity for phospholipids with short acyl chains at the sn-2 position.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Membrane. Endoplasmic reticulum membrane.

Tissue specificity. Broadly expressed in different tissues, but high in B- and T-lymphocytes. In brain, expression is restricted to amygdala and frontal cortex.

Activity regulation. Inhibited by phenylmethanesulfonyl fluoride, 3,4,dichloroisocoumarin, diisopropyl fluorophosphate (DFP) and diethyl p-nitrophenyl phosphate (DENP).

Similarity. Belongs to the serine esterase family.

RefSeq proteins (1): NP_000428* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016715	PAF_acetylhydro_eukaryote	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF03403

Enzyme classification (BRENDA):

• EC 3.1.1.47 — 1-alkyl-2-acetylglycerophosphocholine esterase (BRENDA: 15 organisms, 161 substrates, 92 inhibitors, 50 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-O-ALKYL-2-ACETYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0052–0.392	18
ACETYLATED PLATELET-ACTIVATION FACTOR	0.082–0.206	4
1-PALMITOYL-2-(5-OXOVALEROYL)-SN-GLYCERO-3-PHOSP	0.0193–0.0431	2
F2-ISOPROSTANE-PHOSPHOCHOLINE	—	2
1,2-DIDECANOYL-SN-GLYCEROL	0.011	1
1,2-DIOCTANOYL-SN-GLYCEROL	0.005	1
1,2-DIOCTANOYLETHYLENEGLYCOL	0.005	1
1-ACETYL-2-HEXADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.005	1
1-DECANOYL-RAC-GLYCEROL	0.086	1
1-HEXADECYL-2-ACETYL-SN-GLYCEROL-3-PHOSPHOCHOLIN	0.0031	1
1-OCTANOYL-RAC-GLYCEROL	1.4	1
1-OLEOYL-2-ACETYL-SN-GLYCEROL	0.006	1
2-ACETYL-1-ALKYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0049	1
2-ACETYL-1-HEXADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.005	1
2-ACETYL-1-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.005	1

Catalyzed reactions (Rhea), 10 shown:

• a 1-organyl-2-lyso-sn-glycero-3-phospholipid + a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine = a 1-organyl-2-acetyl-sn-glycero-3-phospholipid + a 1-O-alkyl-sn-glycero-3-phosphocholine (RHEA:11048)
• a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:17777)
• a 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:36231)
• 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:40479)
• 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + a 1-O-(1Z-alkenyl)-sn-glycero-3-phosphoethanolamine = 1-O-(1Z-alkenyl)-2-acetyl-sn-glycero-3-phosphoethanolamine + 1-O-hexadecyl-sn-glycero-3-phosphocholine (RHEA:41396)
• 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + sphing-4-enine = 1-O-hexadecyl-sn-glycero-3-phosphocholine + N-(acetyl)-sphing-4-enine + H(+) (RHEA:41408)
• 1-O-hexadecyl-2-propanoyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + propanoate + H(+) (RHEA:41688)
• 1-O-hexadecyl-2-butanoyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + butanoate + H(+) (RHEA:41692)
• 1-O-hexadecyl-2-succinyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + succinate + H(+) (RHEA:41696)
• 1-O-hexadecyl-2-glutaryl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + glutarate + H(+) (RHEA:41700)

UniProt features (7 total): active site 3, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99487-F1	91.31	0.81

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): 236 (nucleophile); 259 (charge relay system); 314 (charge relay system)

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418346	Platelet homeostasis

MSigDB gene sets: 216 (showing top): HOEGERKORP_CD44_TARGETS_TEMPORAL_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, COUP_01, GOBP_WOUND_HEALING, HNF4_01, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_LIPID_METABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_DN, SANSOM_APC_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, AFFAR_YY1_TARGETS_UP, GOBP_HEMOSTASIS, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GOBP_LIPID_CATABOLIC_PROCESS, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP

GO Biological Process (3): lipid metabolic process (GO:0006629), blood coagulation (GO:0007596), lipid catabolic process (GO:0016042)

GO Molecular Function (5): 1-alkyl-2-acetylglycerophosphocholine esterase activity (GO:0003847), phospholipid binding (GO:0005543), platelet-activating factor acetyltransferase activity (GO:0047179), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (4): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
cellular anatomical structure	2
primary metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
lipid metabolic process	1
catabolic process	1
carboxylic ester hydrolase activity	1
lipid binding	1
acetyltransferase activity	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAFAH2	PAFAH1B1	P43034	838
PAFAH2	ABHD11	Q8NFV4	683
PAFAH2	ABHD13	Q7L211	528
PAFAH2	ABHD6	Q9BV23	522
PAFAH2	NCEH1	Q6PIU2	509
PAFAH2	ZNF222	Q9UK12	506
PAFAH2	PAFAH1B2	P68402	467
PAFAH2	CCDC158	Q5M9N0	459
PAFAH2	APEH	P13798	453
PAFAH2	PNPLA4	P41247	448
PAFAH2	PAFAH1B3	Q15102	430
PAFAH2	MPZL3	Q6UWV2	429
PAFAH2	PLA2G15	Q8NCC3	419
PAFAH2	RIOK3	O14730	412
PAFAH2	GPR63	Q9BZJ6	400

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MRPL51		psi-mi:“MI:0914”(association)	0.350
HES4	CTSV	psi-mi:“MI:0914”(association)	0.350
PAFAH2	CTU2	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): PAFAH2 (Co-fractionation), PAFAH2 (Co-fractionation), DIABLO (Co-fractionation), GRPEL1 (Co-fractionation), IARS2 (Co-fractionation), PFDN4 (Co-fractionation), PAFAH2 (Co-fractionation), PAFAH2 (Co-fractionation), PAFAH2 (Co-fractionation), KIF3A (Affinity Capture-MS), USP28 (Affinity Capture-MS), AGTRAP (Affinity Capture-MS), CTU2 (Affinity Capture-MS), PAFAH2 (Affinity Capture-MS), PAFAH2 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A4D126, A5PKL6, A6QP81, B2GUS6, D2H8V8, E1BCH6, E1BVR9, E9PYK3, F1ND48, G5E8F4, P79106, Q28CZ7, Q32PY6, Q3U269, Q3U3W5, Q3U5Q7, Q3UVV9, Q49MI3, Q4R3W5, Q5F3V0, Q5ND52, Q5R5X9, Q5RCP1, Q5RFM7, Q5RJG7, Q5RL51, Q5S6T3, Q5T8I9, Q5VZV1, Q6AYG3, Q8BIW1, Q8BK58, Q8BQJ6, Q8BTK5, Q8BZ20, Q8C5V5, Q8CAE2, Q8IXQ6, Q8IYR2

Diamond homologs: P70683, P79106, P83006, Q13093, Q22943, Q28017, Q28262, Q60963, Q8VDG7, Q90678, Q99487

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	70
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1072550	NC_000001.10:g.(?25870180)(26795632_?)del	Pathogenic

SpliceAI

1488 predictions. Top by Δscore:

Variant	Effect	Δscore
1:25962079:CAGGT:C	acceptor_gain	1.0000
1:25962080:AGGT:A	acceptor_gain	1.0000
1:25962081:GGT:G	acceptor_gain	1.0000
1:25962081:GGTCT:G	acceptor_loss	1.0000
1:25962082:GT:G	acceptor_gain	1.0000
1:25962082:GTC:G	acceptor_loss	1.0000
1:25962083:TC:T	acceptor_loss	1.0000
1:25962084:C:A	acceptor_loss	1.0000
1:25962084:C:CC	acceptor_gain	1.0000
1:25972710:CCA:C	acceptor_gain	1.0000
1:25972711:CAC:C	acceptor_gain	1.0000
1:25972713:C:CC	acceptor_gain	1.0000
1:25974478:A:AC	donor_gain	1.0000
1:25974479:C:CC	donor_gain	1.0000
1:25974479:CAGAA:C	donor_gain	1.0000
1:25974520:T:C	donor_gain	1.0000
1:25982359:CATA:C	donor_loss	1.0000
1:25982362:AC:A	donor_loss	1.0000
1:25982363:C:CG	donor_loss	1.0000
1:25982477:CCT:C	acceptor_loss	1.0000
1:25982478:CTGCA:C	acceptor_loss	1.0000
1:25982479:T:A	acceptor_loss	1.0000
1:25983944:A:AC	donor_gain	1.0000
1:25983944:AC:A	donor_gain	1.0000
1:25983945:C:CG	donor_gain	1.0000
1:25983945:CC:C	donor_gain	1.0000
1:25983945:CCT:C	donor_gain	1.0000
1:25983945:CCTG:C	donor_gain	1.0000
1:25983945:CCTGG:C	donor_gain	1.0000
1:25984084:GTCC:G	acceptor_gain	1.0000

AlphaMissense

2573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:25989588:C:G	R35P	0.983
1:25976734:A:G	S236P	0.982
1:25974554:G:C	F285L	0.979
1:25974554:G:T	F285L	0.979
1:25974556:A:G	F285L	0.979
1:25982467:C:G	R188P	0.979
1:25984478:A:T	V131D	0.978
1:25989538:A:G	W52R	0.976
1:25989538:A:T	W52R	0.976
1:25972574:G:C	F356L	0.974
1:25972574:G:T	F356L	0.974
1:25972576:A:G	F356L	0.974
1:25972687:C:G	D319H	0.972
1:25984496:G:T	A125D	0.970
1:25989580:A:C	Y38D	0.969
1:25976729:A:C	F237L	0.965
1:25976729:A:T	F237L	0.965
1:25976731:A:G	F237L	0.965
1:25984464:G:C	H136D	0.965
1:25984466:T:A	E135V	0.965
1:25984475:G:T	A132D	0.965
1:25972572:A:G	L357P	0.964
1:25976725:C:A	G239W	0.961
1:25974633:T:A	D259V	0.959
1:25988231:C:A	R114M	0.959
1:25976727:C:A	G238V	0.958
1:25976727:C:T	G238E	0.958
1:25988231:C:G	R114T	0.958
1:25984462:G:C	H136Q	0.957
1:25984462:G:T	H136Q	0.957

dbSNP variants (sampled 300 via entrez): RS1000123505 (1:25979691 T>C), RS1000163277 (1:25998206 G>T), RS1000191127 (1:25981093 T>C), RS1000192541 (1:25965946 A>C), RS1000238911 (1:25962121 T>C), RS1000241889 (1:25978262 T>A), RS1000328980 (1:25998353 G>C), RS1000365228 (1:25959740 T>C,G), RS1000379560 (1:25995508 A>G), RS1000481173 (1:25965519 G>A,C), RS1000584458 (1:25960857 G>A,C), RS1000700587 (1:25961471 C>T), RS1000735036 (1:25997521 C>T), RS1000830548 (1:25997145 G>A), RS1000836798 (1:25972521 C>A,T)

Disease associations

OMIM: gene MIM:602344 | disease phenotypes: MIM:603813

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 4 (MONDO:0011374)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST011836_2	Cervical high-risk human papilloma virus infection (persistent)	8.000000e-06
GCST012490_131	Femur bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Phospholipase A₂

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression, affects cotreatment	1
butyraldehyde	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Ozone	affects expression, increases abundance	1
Phosphatidylcholines	decreases reaction, increases abundance	1
Thiram	decreases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	affects expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
tert-Butylhydroperoxide	affects localization, decreases reaction, increases activity, decreases response to substance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT06535542	Not specified	RECRUITING	Integrating Whole Genome Sequencing and Digital Twins Into the Management of Hypercholesterolemia in Emiratis