PAFAH1B2

Summary

PAFAH1B2 (platelet activating factor acetylhydrolase 1b catalytic subunit 2, HGNC:8575) is a protein-coding gene on chromosome 11q23.3, encoding Platelet-activating factor acetylhydrolase IB subunit alpha2 (P68402). Alpha2 catalytic subunit of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and modulates the action of PAF.

Platelet-activating factor acetylhydrolase (PAFAH) inactivates platelet-activating factor (PAF) into acetate and LYSO-PAF. This gene encodes the beta subunit of PAFAH, the other subunits are alpha and gamma. Multiple alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 5049 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• MANE Select transcript: NM_002572

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8575
Approved symbol	PAFAH1B2
Name	platelet activating factor acetylhydrolase 1b catalytic subunit 2
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168092
Ensembl biotype	protein_coding
OMIM	602508
Entrez	5049

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000304808, ENST00000419197, ENST00000526888, ENST00000527958, ENST00000529887, ENST00000530272, ENST00000533206, ENST00000533677, ENST00000903188, ENST00000903189, ENST00000903190, ENST00000903191, ENST00000903192, ENST00000903193, ENST00000903194, ENST00000903195, ENST00000903196, ENST00000928783, ENST00000928784, ENST00000928785, ENST00000928786, ENST00000928787, ENST00000928788, ENST00000928789, ENST00000928790, ENST00000948517, ENST00000948518, ENST00000948519

RefSeq mRNA: 5 — MANE Select: NM_002572 NM_001184746, NM_001184747, NM_001184748, NM_001309431, NM_002572

CCDS: CCDS53713, CCDS53714, CCDS53715, CCDS8380

Canonical transcript exons

ENST00000527958 — 6 exons

Exon	Start	End
ENSE00001131376	117163770	117163892
ENSE00002164200	117167421	117171045
ENSE00002176941	117144287	117144418
ENSE00003582892	117152441	117152528
ENSE00003593989	117161145	117161261
ENSE00003599941	117159934	117160023

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.4381 / max 2899.4301, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116858	66.8989	1827
116862	11.2979	1542
116859	3.2388	1495
116860	1.0024	582

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.82	gold quality
oocyte	CL:0000023	98.28	gold quality
pons	UBERON:0000988	98.23	gold quality
inferior vagus X ganglion	UBERON:0005363	98.21	gold quality
superior vestibular nucleus	UBERON:0007227	98.12	gold quality
trigeminal ganglion	UBERON:0001675	97.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.85	gold quality
subthalamic nucleus	UBERON:0001906	97.80	gold quality
substantia nigra pars compacta	UBERON:0001965	97.60	gold quality
middle temporal gyrus	UBERON:0002771	97.49	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.42	gold quality
ventral tegmental area	UBERON:0002691	97.41	gold quality
parietal lobe	UBERON:0001872	97.15	gold quality
adult organism	UBERON:0007023	97.10	gold quality
postcentral gyrus	UBERON:0002581	97.04	gold quality
adrenal tissue	UBERON:0018303	96.84	gold quality
dorsal root ganglion	UBERON:0000044	96.82	gold quality
calcaneal tendon	UBERON:0003701	96.62	gold quality
lateral globus pallidus	UBERON:0002476	96.59	gold quality
globus pallidus	UBERON:0001875	96.56	gold quality
medial globus pallidus	UBERON:0002477	96.44	gold quality
pericardium	UBERON:0002407	96.31	gold quality
visceral pleura	UBERON:0002401	96.16	gold quality
cortical plate	UBERON:0005343	96.16	gold quality
corpus callosum	UBERON:0002336	96.14	gold quality
germinal epithelium of ovary	UBERON:0001304	96.10	gold quality
nipple	UBERON:0002030	96.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.98	gold quality
entorhinal cortex	UBERON:0002728	95.89	gold quality
ganglionic eminence	UBERON:0004023	95.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6819	no	940.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

168 targeting PAFAH1B2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 12)

• PAFAH1B2 is not the gene responsible for the linkage evidence on chromosome 11q23 in protein C deficiency. (PMID:17849047)
• splice variants of the Pafah1b2 gene transcript retain exons 1-5 and replace exon 6 with alternative exons derived from genomic sequence 3’ to exon 6. Splice variants encode two proteins with different novel carboxy termini (PMID:18155631)
• These results indicate an antagonistic effect of alpha1, alpha2 and Ndel1 for Lis1 binding, probably to modulate dynein functions in vivo. (PMID:19622634)
• intracellular type I PAF acetylhydrolase (PAFAH1B2 and PAFAH1B3) is the major aspirin hydrolase of human blood (PMID:21844189)
• Plasma PAF-AH can hydrolyze oxidized phospholipids, and may attenuate the spreading of lipid peroxidation and participate in defense mechanisms against vasospasm after aneurysmal subarachnoid hemorrhage. (PMID:21866060)
• Knockdown of PAFAH1B2 strongly reduced Abeta secretion from human cells, and this effect was confirmed in primary cells derived from PAFAH1B2 knock-out mice (PMID:23238734)
• aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. (PMID:23508960)
• The R92H and I198T polymorphisms are highly related to the plasma PAF-AH levels and the risk of coronary heart disease, especially among patients with blood stasis syndrome. (PMID:25034894)
• PAFAH1B2 and 1B3 are important in maintaining cancer pathogenicity across a wide spectrum of cancer types. (PMID:25945974)
• PAF is demonstrated to be the key indicator in the lipid metabolism of polypoidal choroidal vasculopathy patients in this study. (PMID:27910906)
• PAFAH1B2 overexpression in pancreatic ductal adenocarcinoma cells was directly mediated by HIF1a. (PMID:29758199)
• Cathepsin G-induced malignant progression of MCF-7 cells involves suppression of PAF signaling through induced expression of PAFAH1B2. (PMID:35462067)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pafah1b2	ENSDARG00000035352
mus_musculus	Pafah1b2	ENSMUSG00000003131
rattus_norvegicus	Pafah1b2	ENSRNOG00000057102
drosophila_melanogaster	Paf-AHalpha	FBGN0025809

Paralogs (2): PAFAH1B3 (ENSG00000079462), ICE1 (ENSG00000164151)

Protein

Protein identifiers

Platelet-activating factor acetylhydrolase IB subunit alpha2 — P68402 (reviewed: P68402)

Alternative names: PAF acetylhydrolase 30 kDa subunit, PAF-AH subunit beta

All UniProt accessions (3): P68402, J3KNE3, V9HW44

UniProt curated annotations — full annotation on UniProt →

Function. Alpha2 catalytic subunit of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and modulates the action of PAF. The activity and substrate specificity of PAF-AH (I) are affected by its subunit composition. The alpha2/alpha2 homodimer (PAFAH1B2/PAFAH1B2 homodimer) hydrolyzes PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE) more efficiently than 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA). In contrast, the alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B3 heterodimer) hydrolyzes AAGPA more efficiently than PAF, but has little hydrolytic activity towards AAGPE. May play a role in male germ cell meiosis during the late pachytenestage and meiotic divisions as well as early spermiogenesis.

Subunit / interactions. Forms a catalytic dimer which is either homodimer (alpha2/alpha2 homodimer) or heterodimer with PAFAH1B3 (alpha2/alpha1 heterodimer). Component of the cytosolic (PAF-AH (I)) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity. Interacts (homodimer form) with PAFAH1B1 (homodimer form); PAFAH1B2 competes with NDEL1 for PAFAH1B1 binding. Interacts with VLDLR; this interaction may modulate the Reelin pathway.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous.

Activity regulation. Beta subunit (PAFAH1B1) stimulates the acetylhydrolase activity of the alpha2/alpha2 catalytic homodimer.

Miscellaneous. Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively.

Similarity. Belongs to the ‘GDSL’ lipolytic enzyme family. Platelet-activating factor acetylhydrolase IB beta/gamma subunits subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P68402-1	1	yes
P68402-2	2
P68402-3	3
P68402-4	4

RefSeq proteins (5): NP_001171675, NP_001171676, NP_001171677, NP_001296360, NP_002563* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013830	SGNH_hydro	Domain
IPR036514	SGNH_hydro_sf	Homologous_superfamily

Pfam: PF13472

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), 4 shown:

• a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:17777)
• 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-phosphate + H2O = 1-O-hexadecyl-sn-glycero-3-phosphate + acetate + H(+) (RHEA:41704)
• 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphoethanolamine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphoethanolamine + acetate + H(+) (RHEA:41708)

UniProt features (33 total): helix 9, strand 9, modified residue 4, splice variant 3, active site 3, turn 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1VYH	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P68402-F1	94.14	0.91

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): 48; 193; 196

Post-translational modifications (4): 2, 2, 64, 220

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic

MSigDB gene sets: 247 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GCM_BCL2L1, GOBP_MACROAUTOPHAGY, AGGCACT_MIR5153P, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, RICKMAN_METASTASIS_DN

GO Biological Process (4): lipid metabolic process (GO:0006629), spermatogenesis (GO:0007283), lipid catabolic process (GO:0016042), positive regulation of macroautophagy (GO:0016239)

GO Molecular Function (8): 1-alkyl-2-acetylglycerophosphocholine esterase activity (GO:0003847), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), platelet-activating factor acetyltransferase activity (GO:0047179), protein binding (GO:0005515), hydrolase activity (GO:0016787), identical protein binding (GO:0042802)

GO Cellular Component (10): fibrillar center (GO:0001650), extracellular region (GO:0005576), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), 1-alkyl-2-acetylglycerophosphocholine esterase complex (GO:0008247), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein dimerization activity	2
binding	2
primary metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
lipid metabolic process	1
catabolic process	1
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
carboxylic ester hydrolase activity	1
identical protein binding	1
acetyltransferase activity	1
catalytic activity	1
protein binding	1
nucleolus	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
catalytic complex	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAFAH1B2	PAFAH1B1	P43034	951
PAFAH1B2	PAFAH1B3	Q15102	807
PAFAH1B2	NDEL1	Q9GZM8	784
PAFAH1B2	NDE1	Q9NXR1	773
PAFAH1B2	ADRA1D	P25100	647
PAFAH1B2	KIF1A	Q12756	582
PAFAH1B2	KATNA1	O75449	549
PAFAH1B2	DISC1	Q9NRI5	549
PAFAH1B2	TRIM13	O60858	547
PAFAH1B2	NOLC1	Q14978	516
PAFAH1B2	VAMP1	P23763	510
PAFAH1B2	FOXR1	Q6PIV2	506
PAFAH1B2	MKLN1	Q9UL63	490
PAFAH1B2	VLDLR	P98155	486
PAFAH1B2	CIC	Q96RK0	469

IntAct

48 interactions, top by confidence:

A	B	Type	Score
PAFAH1B2	PAFAH1B3	psi-mi:“MI:0915”(physical association)	0.740
PAFAH1B2	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.700
PAFAH1B2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.700
PAFAH1B3	PAFAH1B1	psi-mi:“MI:0914”(association)	0.640
PAFAH1B2	CLVS2	psi-mi:“MI:0915”(physical association)	0.560
PRKN	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.560
PAFAH1B1	DYNLT3	psi-mi:“MI:0914”(association)	0.510
PAFAH1B2	CRK	psi-mi:“MI:0915”(physical association)	0.490
Pafah1b1	EDIL3	psi-mi:“MI:0915”(physical association)	0.400
PAFAH1B2	STAT3	psi-mi:“MI:0915”(physical association)	0.370
Pafah1b1	ATXN3	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
FN1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MCC	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
MPG	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
TRAF6	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
EPB41	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
NME2	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
PRKAB1	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
PAFAH1B1	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000
PAFAH1B2	NDEL1	psi-mi:“MI:0915”(physical association)	0.000
TRIM63	PAFAH1B2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (105): PAFAH1B3 (Two-hybrid), C14orf166 (Co-fractionation), FAM98B (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PAFAH1B2 (Co-fractionation), PSMG1 (Co-fractionation), RTCB (Co-fractionation), SHMT2 (Co-fractionation), VARS (Co-fractionation)

ESM2 similar proteins: A0A5F8AH41, A2BIR6, A5WVX1, B4Q1B6, O35263, O35264, O43252, O54820, P34913, P40935, P52788, P56192, P68401, P68402, P76092, Q06AU9, Q09LX1, Q13057, Q15102, Q29460, Q2T9L8, Q32KX8, Q3SZ16, Q3SZA5, Q3URQ7, Q4WF29, Q5R4G2, Q5R6X1, Q5XJ57, Q5ZMS2, Q60967, Q61205, Q61206, Q63HM1, Q68FL6, Q68LP1, Q6JQN1, Q6PFX8, Q6Q2C2, Q711G3

Diamond homologs: O35263, O35264, P68401, P68402, Q15102, Q29460, Q5R4G2, Q5R6X1, Q5ZMS2, Q61205, Q61206, Q9VXP4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PAFAH1B2	up-regulates	APP

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

802 predictions. Top by Δscore:

Variant	Effect	Δscore
11:117144415:TTCA:T	donor_gain	1.0000
11:117144415:TTCAG:T	donor_loss	1.0000
11:117144416:TCA:T	donor_gain	1.0000
11:117144417:CAGT:C	donor_loss	1.0000
11:117144418:AG:A	donor_loss	1.0000
11:117144419:G:GG	donor_gain	1.0000
11:117152525:TCAG:T	donor_loss	1.0000
11:117152527:AGGT:A	donor_loss	1.0000
11:117152528:GG:G	donor_loss	1.0000
11:117152529:G:GA	donor_loss	1.0000
11:117152536:G:GT	donor_gain	1.0000
11:117152536:G:T	donor_gain	1.0000
11:117159927:A:AG	acceptor_gain	1.0000
11:117159928:A:G	acceptor_gain	1.0000
11:117161144:GATAT:G	acceptor_gain	1.0000
11:117161257:CTAAG:C	donor_loss	1.0000
11:117161258:TAAGG:T	donor_loss	1.0000
11:117161259:AAG:A	donor_loss	1.0000
11:117161261:GG:G	donor_loss	1.0000
11:117161262:G:A	donor_loss	1.0000
11:117161263:T:A	donor_loss	1.0000
11:117161270:A:T	donor_gain	1.0000
11:117161274:T:G	donor_gain	1.0000
11:117163765:TGCA:T	acceptor_loss	1.0000
11:117163766:GCA:G	acceptor_loss	1.0000
11:117163767:CA:C	acceptor_loss	1.0000
11:117163768:A:T	acceptor_loss	1.0000
11:117163769:GGTC:G	acceptor_gain	1.0000
11:117163890:TTGG:T	donor_loss	1.0000
11:117163893:G:GG	donor_gain	1.0000

AlphaMissense

1509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:117161224:G:C	R84T	0.999
11:117159989:G:A	G46E	0.998
11:117161225:A:C	R84S	0.998
11:117161225:A:T	R84S	0.998
11:117163777:T:A	V99D	0.998
11:117159988:G:A	G46R	0.997
11:117159988:G:C	G46R	0.997
11:117159989:G:T	G46V	0.997
11:117161188:G:A	G72E	0.997
11:117163789:G:A	G103E	0.997
11:117167587:A:T	D193V	0.997
11:117167595:C:G	H196D	0.997
11:117161199:G:C	D76H	0.996
11:117163788:G:A	G103R	0.996
11:117163788:G:C	G103R	0.996
11:117163799:C:A	N106K	0.996
11:117163799:C:G	N106K	0.996
11:117167458:G:C	R150T	0.996
11:117167458:G:T	R150M	0.996
11:117167588:T:A	D193E	0.996
11:117167588:T:G	D193E	0.996
11:117152517:T:A	W24R	0.995
11:117152517:T:C	W24R	0.995
11:117159991:G:C	D47H	0.995
11:117159992:A:T	D47V	0.995
11:117161148:T:A	W59R	0.995
11:117161148:T:C	W59R	0.995
11:117161224:G:T	R84I	0.995
11:117161227:T:C	L85P	0.995
11:117163780:T:A	V100D	0.995

dbSNP variants (sampled 300 via entrez): RS1000016010 (11:117143442 A>G), RS1000109490 (11:117153633 T>C), RS1000146117 (11:117172899 C>A,G,T), RS1000165317 (11:117150615 A>G), RS1000308337 (11:117178112 A>G,T), RS1000313850 (11:117167863 A>G), RS1000391223 (11:117150321 G>T), RS1000431307 (11:117148506 G>A,C), RS1000493479 (11:117156071 C>A,T), RS1000534318 (11:117142683 A>G), RS1000681902 (11:117145191 T>G), RS1000714732 (11:117154908 G>A), RS1000726881 (11:117149079 C>A,T), RS1000973678 (11:117160290 C>G), RS1001013247 (11:117162617 A>C,G)

Disease associations

OMIM: gene MIM:602508 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000189_45	Protein quantitative trait loci	6.000000e-09
GCST007267_306	Systolic blood pressure	4.000000e-11
GCST007850_8	HDL cholesterol	2.000000e-10
GCST009159_11	Blood protein levels	7.000000e-09
GCST010002_199	Refractive error	3.000000e-34
GCST010988_429	Adult body size	1.000000e-09
GCST90002396_508	Mean reticulocyte volume	5.000000e-09
GCST90002397_404	Mean spheric corpuscular volume	6.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004460	soluble transferrin receptor measurement
EFO:0006335	systolic blood pressure
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004747	protein measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4463 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4936367	PAFAH1B2		0.00	0
rs7112513	PAFAH1B2		0.00	0

ChEMBL bioactivities

12 potent at pChembl≥5 of 18 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.14	IC50	72	nM	METHOXYARACHIDONOYL FLUOROPHOSPHONATE
5.52	IC50	3000	nM	CHEMBL3827161
5.52	IC50	3000	nM	CHEMBL3828405
5.40	IC50	4000	nM	CHEMBL3827906
5.40	IC50	4000	nM	CHEMBL3827685
5.40	IC50	4000	nM	CHEMBL3827226
5.30	IC50	5000	nM	CHEMBL3828611
5.30	IC50	5000	nM	CHEMBL3828405
5.30	IC50	5000	nM	CHEMBL3827906
5.22	IC50	6000	nM	CHEMBL3827226
5.16	IC50	7000	nM	CHEMBL3827685
5.00	IC50	1e+04	nM	CHEMBL3828744

PubChem BioAssay actives

12 with measured affinity, of 81 total; 8 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
(5Z,8Z,11Z,14Z)-1-[fluoro(methoxy)phosphoryl]icosa-5,8,11,14-tetraene	1312659: Inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	0.0720	uM
2-[4-aminobutyl-[2-[4-aminobutyl-[2-[[2-[[(4-bromophenyl)carbamoylamino]-[2-[[2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetyl]-[(4-chlorobenzoyl)amino]amino]acetyl]amino]acetyl]-(2-methoxyethyl)amino]acetyl]amino]acetyl]amino]acetamide	1312645: Inhibition of FP-Rh probe binding to recombinant PAFAH1B2 (unknown origin) doped in human HeLa cell lysate incubated for 30 mins followed by FP-Rh probe addition measured after 10 mins by ABPP gel-based assay	ic50	3.0000	uM
2-[4-aminobutyl-[2-[4-aminobutyl-[2-[[2-[1,3-benzodioxol-5-ylmethyl-[2-[[2-[[2-[[2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetyl]-(3-methoxypropanoylamino)amino]acetyl]-[(4-chlorobenzoyl)amino]amino]acetyl]-(phenylcarbamoylamino)amino]acetyl]amino]acetyl]-(2-methoxyethyl)amino]acetyl]amino]acetyl]amino]acetamide	1312663: Time-dependent inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	3.0000	uM
2-[4-aminobutyl-[2-[4-aminobutyl-[2-[[2-[[2-[[2-[[2-[[2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetyl]-[(2-phenylacetyl)amino]amino]acetyl]-[(4-chlorobenzoyl)amino]amino]acetyl]-(phenylcarbamoylamino)amino]acetyl]-[(4-methoxybenzoyl)amino]amino]acetyl]-(2-methoxyethyl)amino]acetyl]amino]acetyl]amino]acetamide	1312659: Inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	4.0000	uM
2-[4-aminobutyl-[2-[4-aminobutyl-[2-[[2-[[2-[[2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetyl]-[(4-chlorobenzoyl)amino]amino]acetyl]-[[4-(dimethylamino)phenyl]carbamoylamino]amino]acetyl]-(2-methoxyethyl)amino]acetyl]amino]acetyl]amino]acetamide	1312663: Time-dependent inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	4.0000	uM
2-[4-aminobutyl-[2-[4-aminobutyl-[2-[[2-[[2-[[2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetyl]-[(4-chlorobenzoyl)amino]amino]acetyl]-(phenylcarbamoylamino)amino]acetyl]-(2-methoxyethyl)amino]acetyl]amino]acetyl]amino]acetamide	1312663: Time-dependent inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	4.0000	uM
2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetamide	1312663: Time-dependent inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	5.0000	uM
N-[2-[[2-[[2-[[2-[[2-[[2-[4-aminobutyl-[2-[4-aminobutyl-(2-amino-2-oxoethyl)amino]-2-oxoethyl]amino]-2-oxoethyl]-(2-methoxyethyl)amino]-2-oxoethyl]-[(4-methoxybenzoyl)amino]amino]-2-oxoethyl]-(phenylcarbamoylamino)amino]-2-oxoethyl]-[(4-chlorobenzoyl)amino]amino]-2-oxoethyl]-(3-methoxypropanoylamino)amino]-2-oxoethyl]-2-[5-[5-(4-bromophenyl)thiophen-2-yl]-2-oxo-1,3,4-oxadiazol-3-yl]-N-methylacetamide	1312663: Time-dependent inhibition of PAFAH1B2 (unknown origin) using 2-thiol-PAF as substrate by Ellman’s assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	increases methylation, decreases expression, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
T-2 Toxin	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209094	Binding	Inhibition of PAFAH1B2 binding to FP-biotin in [12C][14N]-lysine, arginine and [13C6][15N2]-lysine, arginine labeled HEK293T cells at 20 uM after 1 hr by isotopic activity-based protein profiling-MudPIT assay	Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. — J Med Chem

Clinical trials (associated diseases)

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