PLA2G4D

Summary

PLA2G4D (phospholipase A2 group IVD, HGNC:30038) is a protein-coding gene on chromosome 15q15.1, encoding Cytosolic phospholipase A2 delta (Q86XP0). Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position.

The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).

Source: NCBI Gene 283748 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 161 total
• Druggable target: yes
• MANE Select transcript: NM_178034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30038
Approved symbol	PLA2G4D
Name	phospholipase A2 group IVD
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	cPLA2delta
Ensembl gene	ENSG00000159337
Ensembl biotype	protein_coding
OMIM	612864
Entrez	283748

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 retained_intron, 1 protein_coding

ENST00000290472, ENST00000560132, ENST00000560932

RefSeq mRNA: 1 — MANE Select: NM_178034 NM_178034

CCDS: CCDS32203

Canonical transcript exons

ENST00000290472 — 20 exons

Exon	Start	End
ENSE00001273549	42067009	42068941
ENSE00001273564	42069909	42070095
ENSE00001337040	42070717	42070883
ENSE00001337043	42072275	42072392
ENSE00001337045	42079537	42079759
ENSE00001337046	42080997	42081133
ENSE00001337047	42081479	42081614
ENSE00001337048	42081797	42081834
ENSE00001337052	42083716	42083779
ENSE00001337054	42085096	42085138
ENSE00001337055	42085491	42085531
ENSE00001337056	42086213	42086344
ENSE00001337057	42087300	42087436
ENSE00001337059	42087628	42087700
ENSE00001337062	42094415	42094562
ENSE00001753568	42071774	42071911
ENSE00003501518	42071123	42071317
ENSE00003636619	42083198	42083334
ENSE00003648304	42082279	42082389
ENSE00003663988	42071444	42071551

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 83.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1210 / max 79.3093, expressed in 19 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149542	0.1210	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	83.45	gold quality
zone of skin	UBERON:0000014	82.96	gold quality
skin of leg	UBERON:0001511	82.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.21	gold quality
lower esophagus mucosa	UBERON:0035834	70.41	gold quality
vagina	UBERON:0000996	69.96	gold quality
esophagus mucosa	UBERON:0002469	58.78	gold quality
pituitary gland	UBERON:0000007	54.75	gold quality
adenohypophysis	UBERON:0002196	53.24	gold quality
prostate gland	UBERON:0002367	52.74	gold quality
ectocervix	UBERON:0012249	50.89	gold quality
endometrium	UBERON:0001295	50.62	gold quality
right adrenal gland cortex	UBERON:0035827	50.48	gold quality
uterine cervix	UBERON:0000002	49.95	gold quality
colonic epithelium	UBERON:0000397	49.69	gold quality
right adrenal gland	UBERON:0001233	49.01	gold quality
stromal cell of endometrium	CL:0002255	48.21	gold quality
adrenal gland	UBERON:0002369	47.53	gold quality
left adrenal gland	UBERON:0001234	47.42	gold quality
mucosa of transverse colon	UBERON:0004991	47.20	gold quality
Ammon’s horn	UBERON:0001954	47.01	gold quality
left adrenal gland cortex	UBERON:0035825	46.96	gold quality
duodenum	UBERON:0002114	46.84	silver quality
esophagus	UBERON:0001043	46.33	gold quality
tonsil	UBERON:0002372	46.02	gold quality
prefrontal cortex	UBERON:0000451	45.10	silver quality
urinary bladder	UBERON:0001255	44.69	gold quality
minor salivary gland	UBERON:0001830	43.68	gold quality
adrenal tissue	UBERON:0018303	43.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting PLA2G4D, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-3908	98.75	67.31	1160

Literature-anchored findings (GeneRIF, showing 4)

• cPLA(2)delta exhibits a unique distribution pattern compared with that of known cPLA(2) subtypes and may play a critical role in inflammation in psoriatic lesions (PMID:14709560)
• study defined eight additional recurrently mutated genes in SMZL; these genes are CREBBP, CBFA2T3, AMOTL1, FAT4, FBXO11, PLA2G4D, TRRAP and USH2A. (PMID:24349473)
• The findings suggest that PLA2 inhibition or CD1a blockade may have therapeutic potential for psoriasis. (PMID:27670592)
• These findings suggested that the polymorphism of PLA2G4D rs4924618 may have a protective influence on the SPTB susceptibility in a Chinese population, supporting a role for genetics in the association between PG synthesis and preterm birth. (PMID:28440406)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla2g4f.1	ENSDARG00000056535
danio_rerio	pla2g4f.2	ENSDARG00000070953
mus_musculus	Pla2g4d	ENSMUSG00000070719
rattus_norvegicus	Pla2g4d	ENSRNOG00000037231

Paralogs (5): PLA2G4C (ENSG00000105499), PLA2G4A (ENSG00000116711), PLA2G4F (ENSG00000168907), PLA2G4E (ENSG00000188089), PLA2G4B (ENSG00000243708)

Protein

Protein identifiers

Cytosolic phospholipase A2 delta — Q86XP0 (reviewed: Q86XP0)

Alternative names: Phospholipase A2 group IVD

All UniProt accessions (1): Q86XP0

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Has a preference for linoleic acid at the sn-2 position.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Tissue specificity. Expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. Strongly expressed in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin.

Activity regulation. Stimulated by cytosolic Ca(2+).

Domain organisation. The N-terminal C2 domain mediates the association with lipid membranes upon calcium binding. An additional second C2 domain may stand in between the C2 domain and the PLA2c domain.

Pathway. Lipid metabolism; fatty acid metabolism.

Miscellaneous. May be due to an intron retention.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86XP0-1	1	yes
Q86XP0-2	2

RefSeq proteins (1): NP_828848* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR002642	LysoPLipase_cat_dom	Domain
IPR016035	Acyl_Trfase/lysoPLipase	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR040723	cPLA2_C2	Domain
IPR041847	C2_cPLA2	Domain

Pfam: PF00168, PF01735, PF18695

Enzyme classification (BRENDA):

• EC 3.1.1.4 — phospholipase A2 (BRENDA: 129 organisms, 452 substrates, 710 inhibitors, 90 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PHOSPHATIDYLCHOLINE	0.05–17	12
1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.94–13.85	7
PHOSPHATIDYLETHANOLAMINE	0.02–10.5	5
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOPHORYLCHOLINE	1.12–5.13	3
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	3–3.92	3
1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.12–3.2	3
1-HEXADECYL-2-ACETYL-SN-GLYCEROL-3-PHOSPHOCHOLIN	0.0137–0.0142	2
1-PALMITOYL-2-ARACHIDONYLPHOSPHATIDYLCHOLINE	0.0016–0.0033	2
LECITHIN	8.3–8.5	2
(3E)-3-[(3AS,7AS)-3-METHYL-2-OXO-6-(PROPAN-2-YLI	0.742	1
(3R,3AS,5AS,8BR)-3,5A,5B-TRIMETHYL-3A,4,5,5A,5B,	0.746	1
(3R,3AS,5AS,9BR)-3,5A,9-TRIMETHYL-3A,4,5,5A-TETR	0.734	1
(3R,3AS,6R,8S,9BS)-6,8-DIHYDROXY-3,6,9-TRIMETHYL	0.744	1
(3R,3AS,6R,8S,9BS)-8-HYDROXY-3,6,9-TRIMETHYL-2-O	0.738	1
(3R,3AS,6R,9BS)-3,6,9-TRIMETHYL-2,8-DIOXO-2,3,3A	0.742	1

Catalyzed reactions (Rhea), 6 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:15801)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:38779)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40427)
• 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-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:40811)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z,12Z)-octadecadienoate + H(+) (RHEA:40815)

UniProt features (103 total): strand 43, helix 26, binding site 9, turn 9, sequence variant 7, domain 2, sequence conflict 2, splice variant 2, active site 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5IZ5	X-RAY DIFFRACTION	2.2
5IXC	X-RAY DIFFRACTION	2.65
5IZR	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XP0-F1	91.26	0.78

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): 361 (nucleophile); 647 (proton acceptor)

Ligand- & substrate-binding residues (9): 96; 96; 102; 330–331; 38; 38; 44; 94; 94

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482801	Acyl chain remodelling of PS
R-HSA-1482839	Acyl chain remodelling of PE
R-HSA-1482922	Acyl chain remodelling of PI
R-HSA-1482925	Acyl chain remodelling of PG
R-HSA-1483115	Hydrolysis of LPC
R-HSA-1483166	Synthesis of PA

MSigDB gene sets: 73 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, LFA1_Q6, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_CATABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_CATABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_ACYL_CHAIN_REMODELING, GOBP_LIPID_CATABOLIC_PROCESS

GO Biological Process (8): fatty acid metabolic process (GO:0006631), phosphatidylglycerol acyl-chain remodeling (GO:0036148), phosphatidylinositol acyl-chain remodeling (GO:0036149), glycerophospholipid catabolic process (GO:0046475), lipid metabolic process (GO:0006629), glycerophospholipid metabolic process (GO:0006650), phospholipid catabolic process (GO:0009395), lipid catabolic process (GO:0016042)

GO Molecular Function (8): calcium ion binding (GO:0005509), calcium-dependent phospholipid binding (GO:0005544), glycerophospholipid phospholipase A1 activity (GO:0008970), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), glycerophospholipase activity (GO:0004620), A2-type glycerophospholipase activity (GO:0004623), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	7

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lipid metabolic process	2
phospholipid metabolic process	2
monocarboxylic acid metabolic process	1
phosphatidylglycerol metabolic process	1
phosphatidylinositol metabolic process	1
glycerophospholipid metabolic process	1
phospholipid catabolic process	1
glycerolipid catabolic process	1
primary metabolic process	1
glycerolipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
catabolic process	1
metal ion binding	1
phospholipid binding	1
A1-type glycerophospholipase activity	1
phospholipase activity	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G4D	PLA2G5	P39877	957
PLA2G4D	ADAMTSL5	Q6ZMM2	685
PLA2G4D	PLA2G2F	Q9BZM2	500
PLA2G4D	PLA2G2A	P14555	490
PLA2G4D	CHPT1	Q8WUD6	452
PLA2G4D	PLA2G6	O60733	451
PLA2G4D	CAMP	P49913	444
PLA2G4D	PLA2G2E	Q9NZK7	432
PLA2G4D	NIM1K	Q8IY84	430
PLA2G4D	PNPLA8	Q9NP80	416
PLA2G4D	LACTBL1	A8MY62	407
PLA2G4D	PLA2G15	Q8NCC3	404
PLA2G4D	PLA2G2D	Q9UNK4	402
PLA2G4D	KRT17	Q04695	396
PLA2G4D	PNPLA6	Q8IY17	392

IntAct

26 interactions, top by confidence:

A	B	Type	Score
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
PLA2G4D	GOT1	psi-mi:“MI:0915”(physical association)	0.400
ATG16L1		psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
GABPA	A2ML1	psi-mi:“MI:0914”(association)	0.350
HCN1	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST7	A2ML1	psi-mi:“MI:0914”(association)	0.350
GUCY1A1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
RNF115	IGLC7	psi-mi:“MI:0914”(association)	0.350
CERS3	IGLC7	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PHF11	A2ML1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
BPHL	SULT2B1	psi-mi:“MI:0914”(association)	0.350
SLC37A4	KLK10	psi-mi:“MI:0914”(association)	0.350
PLA2G4D	GSTZ1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), GOT1 (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), PLA2G4D (Affinity Capture-MS), SLC25A6 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A0PJX2, A2ACG1, D3ZBP4, E2RDP2, F1MH07, O08644, O75038, O75064, O75636, P0C0K7, P0DPD7, P0DPE0, P0DPE1, P52824, Q00653, Q0IID2, Q1LWV7, Q3SYT1, Q3U1Y4, Q4KM32, Q4R380, Q5NCQ5, Q5RKI3, Q62137, Q684M2, Q68DD2, Q6ZSI9, Q86TL0, Q86XP0, Q8BGV9, Q8BX80, Q8C9V1, Q8NFF5, Q8NFI3, Q8R5G7, Q8TDZ2, Q8VDP3, Q8WWN8, Q91ZJ0

Diamond homologs: A0FGR8, A0JJX5, A2X479, A8KBH6, B6ETT4, D4ABL6, E9PV86, O14065, P05126, P05696, P05771, P05772, P10102, P17252, P20444, P68403, P68404, Q3TZZ7, Q5FWL4, Q5M7N9, Q5RJH2, Q6DN12, Q6DN14, Q6YWF1, Q7XA06, Q7ZWU7, Q86KB1, Q86XP0, Q8L706, Q8L7A4, Q8LFN9, Q9C6B7, Q9C8Y2, Q9FHP6, Q9FIK8, Q9FVJ3, Q9LP65, Q9LVH4, Q9M2D4, Q9NZM1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	136
Likely benign	13
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3654 predictions. Top by Δscore:

Variant	Effect	Δscore
15:42070713:GTAC:G	donor_loss	1.0000
15:42070714:TA:T	donor_loss	1.0000
15:42070715:ACCTC:A	donor_loss	1.0000
15:42070716:CC:C	donor_loss	1.0000
15:42070880:TAGT:T	acceptor_gain	1.0000
15:42070882:GT:G	acceptor_gain	1.0000
15:42070882:GTC:G	acceptor_loss	1.0000
15:42070883:TCT:T	acceptor_loss	1.0000
15:42070884:C:CC	acceptor_gain	1.0000
15:42070884:C:CG	acceptor_loss	1.0000
15:42070885:T:A	acceptor_loss	1.0000
15:42071438:TCCCA:T	donor_loss	1.0000
15:42071439:CCCAC:C	donor_loss	1.0000
15:42071440:CCA:C	donor_loss	1.0000
15:42071441:CACCT:C	donor_loss	1.0000
15:42071442:A:AT	donor_loss	1.0000
15:42071443:C:T	donor_loss	1.0000
15:42071446:AAGCT:A	donor_gain	1.0000
15:42071447:AGCT:A	donor_gain	1.0000
15:42071450:T:TA	donor_gain	1.0000
15:42071461:T:TA	donor_gain	1.0000
15:42071547:GATGG:G	acceptor_gain	1.0000
15:42071548:ATGG:A	acceptor_gain	1.0000
15:42071549:TGG:T	acceptor_gain	1.0000
15:42071550:GG:G	acceptor_gain	1.0000
15:42071550:GGCTG:G	acceptor_loss	1.0000
15:42071551:GC:G	acceptor_loss	1.0000
15:42071552:C:CC	acceptor_gain	1.0000
15:42071769:CTCA:C	donor_loss	1.0000
15:42071770:TCA:T	donor_loss	1.0000

AlphaMissense

5303 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:42081545:C:A	R297S	0.987
15:42081545:C:G	R297S	0.987
15:42071909:A:G	W480R	0.983
15:42071909:A:T	W480R	0.983
15:42081546:C:A	R297M	0.982
15:42079728:A:G	W376R	0.980
15:42079728:A:T	W376R	0.980
15:42081546:C:G	R297T	0.980
15:42087341:A:G	W72R	0.978
15:42087341:A:T	W72R	0.978
15:42071541:G:C	S528R	0.971
15:42071541:G:T	S528R	0.971
15:42071543:T:G	S528R	0.971
15:42079726:C:A	W376C	0.971
15:42079726:C:G	W376C	0.971
15:42087339:C:A	W72C	0.971
15:42087339:C:G	W72C	0.971
15:42071829:G:C	F506L	0.970
15:42071829:G:T	F506L	0.970
15:42071831:A:G	F506L	0.970
15:42071898:G:C	F483L	0.970
15:42071898:G:T	F483L	0.970
15:42071900:A:G	F483L	0.970
15:42080998:A:G	W365R	0.970
15:42080998:A:T	W365R	0.970
15:42071546:A:G	W527R	0.965
15:42071546:A:T	W527R	0.965
15:42085506:A:G	F138S	0.964
15:42072339:G:C	N457K	0.963
15:42072339:G:T	N457K	0.963

dbSNP variants (sampled 300 via entrez): RS1000003349 (15:42090691 G>A), RS1000105278 (15:42085264 G>A), RS1000364717 (15:42094145 G>A,T), RS1000439759 (15:42084160 A>G), RS1000632789 (15:42069167 C>T), RS1000635814 (15:42074954 C>T), RS1000707863 (15:42075267 G>C,T), RS1000779823 (15:42095553 T>C,G), RS1000969798 (15:42095545 A>G,T), RS1001041955 (15:42085434 C>T), RS1001062483 (15:42095179 G>C), RS1001228240 (15:42077265 A>G), RS1001273573 (15:42091543 A>G), RS1001558703 (15:42080933 G>A,T), RS1001647306 (15:42093361 G>C)

Disease associations

OMIM: gene MIM:612864 | 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): CHEMBL2287 (SINGLE PROTEIN)

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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Estradiol	increases expression, affects binding	2
sodium arsenate	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
abrine	increases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Copper	affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	increases expression	1
Triclosan	increases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	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
CHEMBL4626967	Binding	Inhibition of human PLA2G4D expressed in HEK293T cell lysates at 10 uM preincubated for 30 mins followed by FP-TAMRA addition and measured after 20 mins by SDS-PAGE based competitive ABPP analysis	Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family. — J Med Chem

Clinical trials (associated diseases)

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