PLAA

Summary

PLAA (phospholipase A2 activating protein, HGNC:9043) is a protein-coding gene on chromosome 9p21.2, encoding Phospholipase A-2-activating protein (Q9Y263). Plays a role in protein ubiquitination, sorting and degradation through its association with VCP.

Enables phospholipase A2 activator activity. Involved in cellular response to lipopolysaccharide and macroautophagy. Located in several cellular components, including cytosol; extracellular exosome; and nucleoplasm.

Source: NCBI Gene 9373 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 618 total — 9 pathogenic, 4 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 10 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 84
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.68 (unconstrained)
• MANE Select transcript: NM_001031689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9043
Approved symbol	PLAA
Name	phospholipase A2 activating protein
Location	9p21.2
Locus type	gene with protein product
Status	Approved
Aliases	PLAP, PLA2P, FLJ11281, FLJ12699, DOA1
Ensembl gene	ENSG00000137055
Ensembl biotype	protein_coding
OMIM	603873
Entrez	9373

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 22 protein_coding, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000397292

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 1, TSL 5: 2

ENST00000397292, ENST00000487173, ENST00000517642, ENST00000520641, ENST00000520884, ENST00000521968, ENST00000523212, ENST00000897950, ENST00000897951, ENST00000897952, ENST00000897953, ENST00000929589, ENST00000929590, ENST00000970087, ENST00000970088, ENST00000970089, ENST00000970090, ENST00000970091, ENST00000970092, ENST00000970093, ENST00000973401, ENST00000973402, ENST00000973403, ENST00001056714, ENST00001056719, ENST00001056721, ENST00001056722, ENST00001105886, ENST00001105887, ENST00001128217, ENST00001140175

RefSeq mRNA: 2 — MANE Select: NM_001031689 NM_001031689, NM_001321546

CCDS: CCDS35000

Canonical transcript exons

ENST00000397292 — 14 exons

Exon	Start	End
ENSE00000928010	26907834	26907998
ENSE00000928011	26910338	26910439
ENSE00000928012	26913879	26913947
ENSE00000928014	26919310	26919529
ENSE00000928015	26920227	26920384
ENSE00000928016	26923178	26923347
ENSE00000928017	26925825	26925960
ENSE00000928018	26926393	26926560
ENSE00000928019	26928100	26928220
ENSE00000928020	26928308	26928408
ENSE00001483692	26903372	26906076
ENSE00001609226	26935013	26935206
ENSE00001640499	26946897	26947242
ENSE00003688392	26917097	26917165

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 93.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6502 / max 252.8718, expressed in 1810 samples.

Highest expression (Bgee): gastrocnemius, secondary oocyte, muscle of leg, adrenal tissue, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLAA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.0e-04	+0.13	9:26987029:G:A
Artery Aorta	eqtl	3.9e-03	+0.15	9:26962490:A:G
Spleen	eqtl	4.2e-03	-0.42	9:27226709:A:G
Cells Cultured fibroblasts	eqtl	8.1e-03	+0.12	9:26931139:T:C
Whole Blood	eqtl	1.9e-02	+0.09	9:27196619:C:T
Muscle Skeletal	eqtl	2.2e-02	+0.11	9:27766078:A:C
Skin Sun Exposed Lower leg	eqtl	3.2e-02	+0.38	9:26363274:A:G
Skin Not Sun Exposed Suprapubic	eqtl	3.8e-02	+0.46	9:25983147:C:T
Esophagus Mucosa	eqtl	4.1e-02	+0.13	9:27027242:T:C
Artery Tibial	eqtl	4.9e-02	-0.08	9:27101038:G:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
100317	18.3859	1799
100318	7.6558	1774
100320	0.7483	503
100321	0.3367	146
100319	0.2934	134
100316	0.2301	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	93.08	gold quality
secondary oocyte	CL:0000655	92.70	gold quality
muscle of leg	UBERON:0001383	92.48	gold quality
adrenal tissue	UBERON:0018303	91.18	gold quality
cortical plate	UBERON:0005343	91.17	gold quality
stromal cell of endometrium	CL:0002255	90.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.24	gold quality
ganglionic eminence	UBERON:0004023	89.83	gold quality
monocyte	CL:0000576	89.79	gold quality
ventricular zone	UBERON:0003053	89.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.29	gold quality
mononuclear cell	CL:0000842	89.26	gold quality
leukocyte	CL:0000738	88.97	gold quality
calcaneal tendon	UBERON:0003701	88.77	gold quality
muscle organ	UBERON:0001630	88.73	gold quality
islet of Langerhans	UBERON:0000006	88.53	gold quality
right adrenal gland cortex	UBERON:0035827	88.15	gold quality
left adrenal gland	UBERON:0001234	87.72	gold quality
right adrenal gland	UBERON:0001233	87.68	gold quality
rectum	UBERON:0001052	87.45	gold quality
adrenal gland	UBERON:0002369	87.36	gold quality
popliteal artery	UBERON:0002250	87.10	gold quality
tibial artery	UBERON:0007610	87.10	gold quality
left adrenal gland cortex	UBERON:0035825	87.04	gold quality
oocyte	CL:0000023	86.41	gold quality
heart left ventricle	UBERON:0002084	86.34	gold quality
right atrium auricular region	UBERON:0006631	86.23	gold quality
lower esophagus mucosa	UBERON:0035834	86.23	gold quality
aorta	UBERON:0000947	86.22	gold quality
gall bladder	UBERON:0002110	86.11	gold quality
right coronary artery	UBERON:0001625	86.03	gold quality
buccal mucosa cell	CL:0002336	85.94	gold quality
adrenal cortex	UBERON:0001235	85.92	gold quality
cardiac ventricle	UBERON:0002082	85.86	gold quality
esophagus mucosa	UBERON:0002469	85.84	gold quality
left coronary artery	UBERON:0001626	85.58	gold quality
skin of leg	UBERON:0001511	85.51	gold quality
skin of abdomen	UBERON:0001416	85.48	gold quality
descending thoracic aorta	UBERON:0002345	85.43	gold quality
biceps brachii	UBERON:0001507	85.35	gold quality
esophagus	UBERON:0001043	85.33	gold quality
thoracic aorta	UBERON:0001515	85.33	gold quality
ascending aorta	UBERON:0001496	85.32	gold quality
body of uterus	UBERON:0009853	85.22	gold quality
heart	UBERON:0000948	85.07	gold quality
mucosa of transverse colon	UBERON:0004991	85.06	gold quality
ectocervix	UBERON:0012249	84.90	gold quality
minor salivary gland	UBERON:0001830	84.85	gold quality
lower esophagus	UBERON:0013473	84.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.66	gold quality
tibial nerve	UBERON:0001323	84.40	gold quality
right lung	UBERON:0002167	84.40	gold quality
vagina	UBERON:0000996	84.38	gold quality
cardiac atrium	UBERON:0002081	84.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.26	gold quality
bone marrow cell	CL:0002092	84.22	gold quality
upper lobe of left lung	UBERON:0008952	84.20	gold quality
coronary artery	UBERON:0001621	84.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.10	gold quality
zone of skin	UBERON:0000014	84.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.95	gold quality
left uterine tube	UBERON:0001303	83.80	gold quality
smooth muscle tissue	UBERON:0001135	83.78	gold quality
pancreas	UBERON:0001264	83.76	gold quality
transverse colon	UBERON:0001157	83.75	gold quality
omental fat pad	UBERON:0010414	83.72	gold quality
mouth mucosa	UBERON:0003729	83.70	gold quality
peritoneum	UBERON:0002358	83.68	gold quality
upper lobe of lung	UBERON:0008948	83.68	gold quality
endocervix	UBERON:0000458	83.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.63	gold quality
vermiform appendix	UBERON:0001154	83.60	gold quality
skeletal muscle tissue	UBERON:0001134	83.49	gold quality
right lobe of liver	UBERON:0001114	83.41	gold quality
body of stomach	UBERON:0001161	83.37	gold quality
metanephros cortex	UBERON:0010533	83.32	gold quality
sigmoid colon	UBERON:0001159	83.25	gold quality
mucosa of stomach	UBERON:0001199	83.24	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.23	gold quality
apex of heart	UBERON:0002098	83.21	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.20	gold quality
body of pancreas	UBERON:0001150	83.14	gold quality
colon	UBERON:0001155	83.12	gold quality
esophagus squamous epithelium	UBERON:0006920	82.98	gold quality
embryo	UBERON:0000922	82.93	gold quality
large intestine	UBERON:0000059	82.92	gold quality
right ovary	UBERON:0002118	82.77	gold quality
left ovary	UBERON:0002119	82.75	gold quality
intestine	UBERON:0000160	82.61	gold quality
colonic epithelium	UBERON:0000397	82.59	gold quality
right lobe of thyroid gland	UBERON:0001119	82.50	gold quality
deltoid	UBERON:0001476	82.49	silver quality
stomach	UBERON:0000945	82.44	gold quality
left lobe of thyroid gland	UBERON:0001120	82.44	gold quality
prefrontal cortex	UBERON:0000451	82.23	gold quality
tendon	UBERON:0000043	82.14	gold quality
lymph node	UBERON:0000029	82.10	gold quality
ovary	UBERON:0000992	82.05	gold quality
tonsil	UBERON:0002372	81.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.68

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	39.7	high
Skeletal muscle	tissue	35.1	low
Tongue	tissue	27.2
Choroid plexus	tissue	24.8
Locus coeruleus	tissue	23.7
Frontal cortex	tissue	23.0
Postcentral gyrus	tissue	22.4
Hippocampus	tissue	22.2	medium
Nucleus accumbens	tissue	22.0
Caudate putamen	tissue	22.0
Hippocampal formation	tissue	21.6
Putamen	tissue	21.0
Pons	tissue	20.4
Midbrain	tissue	20.3
Thalamus	tissue	20.2
Liver	tissue	20.1	not detected
Hypothalamus	tissue	19.3
Spinal cord	tissue	19.3
Superior colliculi	tissue	19.2
Testis	tissue	19.0	high
Medulla oblongata	tissue	19.0
Substantia nigra	tissue	18.9
Cerebral cortex	tissue	18.7	high
Motor cortex	tissue	18.7
Septum	tissue	18.6
Somatosensory cortex	tissue	18.5
Ventral forebrain	tissue	18.1
Smooth muscle	tissue	18.0	not detected
Prefrontal cortex	tissue	17.9
Esophagus	tissue	17.7	not detected
Retrosplenial and cingulate cortex	tissue	17.7
Occipital cortex	tissue	17.7
Heart muscle	tissue	17.6	low
Temporal cortex	tissue	17.1
Tonsil	tissue	17.0	medium
Entorhinal cortex	tissue	17.0
Retrosplenial cortex	tissue	17.0
Thymus	tissue	16.8
Cerebellum	tissue	16.6	low
Periaqueductal gray	tissue	16.6
Insular cortex	tissue	16.6
Amygdala	tissue	16.5
Endometrium 1	tissue	16.4	medium
Corpus callosum	tissue	16.3
Parathyroid gland	tissue	15.9	medium
Adrenal gland	tissue	15.9	medium
Basal ganglia	tissue	15.5	low
Olfactory bulb	tissue	15.4
Appendix	tissue	15.3	medium
Adipose tissue	tissue	15.0	medium
Placenta	tissue	15.0	medium
Rectum	tissue	14.9	medium
Thyroid gland	tissue	14.9	medium
Kidney	tissue	14.3	medium
Colon	tissue	14.2	medium
Lymph node	tissue	14.0	medium
Urinary bladder	tissue	13.7	medium
Retina	tissue	13.0
Duodenum	tissue	12.7	medium
Epididymis	tissue	12.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Lateral hypothalamic area (24.9), Parieto-temporal junction (white matter) (24.7), Corpus callosum, splenium (white matter) (24.4), Arcuate nucleus (24.1), Hippocampus, CA1 (24.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

Targeting PLAA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 122 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850

Functional genomics

gnomAD constraint: pLI 0.00238, LOEUF 0.678, missense Z 0.691 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000397292 — one region, missense o/e 0.95.

Literature-anchored findings (GeneRIF, showing 9)

• Function assignment to conserved residues in mammalian alkaline phosphatases. (PMID:11937510)
• PLAP inhibits sPLA2-triggered release of fatty acids from erythrocyte membranes (PMID:14499668)
• identified one stimulatory element, with Sp1 binding sites, and one inhibitory element, in exon 1 of the plaa gene (PMID:18291623)
• Structural basis for ubiquitin recognition by a novel domain from the human phospholipase A2-activating protein (PMID:19423704)
• This review provides evidence that 1,25-dihydroxy vitamin D3 stimulates PLA2 via PLAA and CaMKII, a process initiated by Pdia3/PLAA interaction, which further triggers CaMKII-dependent PLA2 activation. [review] (PMID:25448737)
• Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. (PMID:27753622)
• This study presented that Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy. (PMID:28007986)
• In both human and mouse, hypomorphic mutations in the ubiquitin adaptor protein PLAA cause an infantile-lethal neurodysfunction syndrome with seizures. (PMID:28413018)
• PLAA suppresses ovarian cancer metastasis via METTL3-mediated m(6)A modification of TRPC3 mRNA. (PMID:35869392)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plaa	ENSDARG00000042728
mus_musculus	Plaa	ENSMUSG00000028577
rattus_norvegicus	Plaa	ENSRNOG00000007753
drosophila_melanogaster	Plap	FBGN0024314
caenorhabditis_elegans		WBGENE00007333

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104810) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 31 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	2
kyphosis	1
tremors	1
weakness	1
paralysis	1
decreased brain size	1
decreased corpus callosum size	1
small cerebellum	1
abnormal Purkinje cell morphology	1
abnormal neuromuscular synapse morphology	1
decreased body weight	1
ataxia	1
decreased locomotor activity	1
abnormal gait	1
limb grasping	1
impaired balance	1
respiratory distress	1
gliosis	1
abnormal PNS synaptic transmission	1
skeletal muscle necrosis	1
abnormal miniature endplate potential	1
abnormal vesicle-mediated transport	1
abnormal Purkinje cell dendrite morphology	1
decreased survivor rate	1
decreased skeletal muscle fiber diameter	1

+6 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila virilis	B4LS78	92.4%	Diamond
Xenopus laevis	Q6GM65	72.6%	Diamond
Oryza sativa Japonica Group	Q9AV81	71.0%	Diamond
Schizosaccharomyces pombe 972h-	O94289	38.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LRRC19	protein-coding	64922
IFT74	protein-coding	80173
IFT74-AS1	ncRNA	101929602
CAAP1	protein-coding	79886
TEK	protein-coding	7010

Protein

Protein identifiers

Phospholipase A-2-activating protein — Q9Y263 (reviewed: Q9Y263)

All UniProt accessions (5): E5RIM3, Q9Y263, H0YAU9, H0YBW4, H0YC16

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in protein ubiquitination, sorting and degradation through its association with VCP. Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. Plays a role in cerebellar Purkinje cell development. Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis.

Subunit / interactions. Interacts with ubiquitin. Interacts with UBXN6, VCP and YOD1; may form a complex involved in macroautophagy.

Subcellular location. Nucleus. Cytoplasm. Synapse.

Disease relevance. Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA) [MIM:617527] An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound intellectual disability and severely impaired or absent motor function. More variable features include seizures and optic atrophy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus. The PFU domain mediates interaction with ubiquitin.

Induction. Up-regulated by tumor necrosis factor alpha (TNF) (at protein level).

Similarity. Belongs to the WD repeat PLAP family.

RefSeq proteins (2): NP_001026859, NP_001308475 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR013535	PUL_dom	Domain
IPR015155	PFU	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR038122	PFU_sf	Homologous_superfamily

Pfam: PF00400, PF08324, PF09070

UniProt features (61 total): helix 22, repeat 13, sequence conflict 11, strand 5, turn 3, modified residue 2, sequence variant 2, domain 2, chain 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
3EBB	PLAP/P97 complex	X-RAY DIFFRACTION	1.9
2K89	Solution structure of a novel Ubiquitin-binding domain from Human PLAA (PFUC, Gly76-Pro77 …	SOLUTION NMR
2K8A	Solution structure of a novel Ubiquitin-binding domain from Human PLAA (PFUC, Gly76-Pro77 …	SOLUTION NMR
2K8B	Solution structure of PLAA family ubiquitin binding domain (PFUC) cis isomer in complex …	SOLUTION NMR
2K8C	Solution structure of PLAA family ubiquitin binding domain (PFUC) trans isomer in complex …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y263-F1	84.87	0.58

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2)

Type	Positions
Phosphoserine	50
N6-acetyllysine	529

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 416 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (14): phospholipid metabolic process (GO:0006644), signal transduction (GO:0007165), nervous system development (GO:0007399), ubiquitin recycling (GO:0010992), macroautophagy (GO:0016236), positive regulation of prostaglandin biosynthetic process (GO:0031394), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), protein unfolding (GO:0043335), cellular response to lipopolysaccharide (GO:0071222), negative regulation of protein K63-linked ubiquitination (GO:1900045), positive regulation of synaptic vesicle recycling (GO:1903423), positive regulation of dendrite extension (GO:1903861), positive regulation of neuron migration (GO:2001224)

GO Molecular Function (3): phospholipase A2 activator activity (GO:0016005), ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasmic ubiquitin ligase complex (GO:0000153), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), synapse (GO:0045202), extracellular exosome (GO:0070062)

GO top-level categories

50 GO namespaces:

Category	Terms
cellular anatomical structure	3
cellular process	2
ubiquitin-dependent protein catabolic process	2
cytoplasm	2
lipid metabolic process	1
organophosphate metabolic process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
animal gross anatomical part developmental process	1
cellular homeostasis	1
autophagosome assembly	1
autophagy	1
prostaglandin biosynthetic process	1
regulation of prostaglandin biosynthetic process	1
positive regulation of unsaturated fatty acid biosynthetic process	1
proteasomal protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
protein K63-linked ubiquitination	1
regulation of protein K63-linked ubiquitination	1
negative regulation of protein polyubiquitination	1
synaptic vesicle recycling	1
positive regulation of transport	1
regulation of synaptic vesicle recycling	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
dendrite extension	1
regulation of dendrite extension	1
neuron migration	1
positive regulation of cell migration	1
regulation of neuron migration	1
A2-type glycerophospholipase activity	1
phospholipase activator activity	1
ubiquitin-like protein binding	1
binding	1
ubiquitin ligase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell junction	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to lipopolysaccharide	BP	mutant phenotype
macroautophagy	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
phospholipase A2 activator activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,332 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAA	UBXN6	Q9BZV1	762
PLAA	UFD1	Q92890	711
PLAA	NPLOC4	Q8TAT6	659
PLAA	YOD1	Q5VVQ6	657
PLAA	VCP	P55072	647
PLAA	ANKZF1	Q9H8Y5	598
PLAA	SPRTN	Q9H040	536
PLAA	UBXN7	O94888	526
PLAA	UBE4A	Q14139	524
PLAA	FAF2	Q96CS3	510
PLAA	UBE4B	O95155	506
PLAA	UBXN1	Q04323	501
PLAA	PDIA3	P30101	444
PLAA	FAF1	Q9UNN5	435
PLAA	DERL1	Q9BUN8	404

IntAct

Human interaction partners of PLAA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
VCP	physical association	0.830	6
UBXN1	physical association	0.670	6
DDIT4L	physical association	0.560	3
KPNA4	physical association	0.560	3
DISC1	physical association	0.000	1

BioGRID (147 interactions; top human partners by supporting records): VCP (Two-hybrid; 9 records), HDAC6 (Affinity Capture-MS; 4 records), LYPD3 (Affinity Capture-MS; 3 records), SRPRB (Affinity Capture-MS; 3 records), UBC (Reconstituted Complex; 3 records), UBXN1 (Two-hybrid; 3 records), CD70 (Affinity Capture-MS; 2 records), CD79B (Affinity Capture-MS; 2 records), LAMP1 (Affinity Capture-MS; 2 records), MILR1 (Affinity Capture-MS; 2 records), NSFL1C (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PDIA3 (Affinity Capture-Western; 2 records), SCN2B (Affinity Capture-MS; 2 records), SIGLEC12 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for PLAA: 618 ClinVar records (13 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	4
Uncertain significance	282
Likely benign	273
Benign	9

Top pathogenic / likely-pathogenic (13)

Showing all 13 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1806265	NM_001031689.3(PLAA):c.1570C>T (p.Arg524Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
807466	NM_001031689.3(PLAA):c.240_241insTAG (p.Pro81Ter)	Pathogenic	criteria provided, single submitter	1
828067	NM_001031689.3(PLAA):c.120C>G (p.Asp40Glu)	Pathogenic	criteria provided, single submitter	1
3307234	NM_001031689.3(PLAA):c.802C>T (p.Arg268Ter)	Pathogenic	criteria provided, single submitter	1
694395	NM_001031689.3(PLAA):c.2350del (p.Lys783_Val784insTer)	Likely pathogenic	criteria provided, single submitter	1
1333605	NM_001031689.3(PLAA):c.850_860del (p.Asp284fs)	Likely pathogenic	criteria provided, single submitter	1
2497674	NM_001031689.3(PLAA):c.1800G>A (p.Trp600Ter)	Likely pathogenic	criteria provided, single submitter	1
1299891	NM_001031689.3(PLAA):c.861T>A (p.Val287=)	Pathogenic	no assertion criteria provided	2
427940	NM_001031689.3(PLAA):c.2254C>T (p.Leu752Phe)	Pathogenic	no assertion criteria provided	1
427941	NM_001031689.3(PLAA):c.68G>T (p.Gly23Val)	Pathogenic	no assertion criteria provided	1
427942	NM_001031689.3(PLAA):c.68dup (p.Leu24fs)	Pathogenic	no assertion criteria provided	1
975038	NM_001031689.3(PLAA):c.1049A>T (p.Glu350Val)	Pathogenic	no assertion criteria provided	1
975039	NM_001031689.3(PLAA):c.829T>C (p.Cys277Arg)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PLAA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,192):

Position(s)	Effect	Δscore	Sites
9:26910336–26910337	donor_loss	1.0000	4
9:26913877–26913878	donor_loss	1.0000	5
9:26913948–26913949	acceptor_loss	1.0000	6
9:26919308–26919309	donor_loss	1.0000	4
9:26920229–26920230	donor_gain	1.0000	2
9:26923176	donor_loss	1.0000
9:26923348	acceptor_loss	1.0000	3
9:26923350	acceptor_gain	1.0000
9:26926391–26926392	donor_loss	1.0000	5
9:26926561–26926562	acceptor_loss	1.0000	3

AlphaMissense

1,852 missense substitutions predicted likely pathogenic (of 5,223 scored), across 476 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D132	8	0.994	0.999
H111	8	0.993	0.997
D211	8	0.992	0.999
D172	8	0.991	0.999
D615	8	0.990	0.996
H150	8	0.989	0.996
D40	8	0.985	0.997
D91	8	0.985	0.998
D252	8	0.984	0.998
H190	8	0.983	0.994
F405	8	0.980	0.998
D20	8	0.978	0.992
D469	8	0.968	0.988
H230	8	0.966	0.990
F433	8	0.964	0.999
H17	8	0.961	0.983
N210	8	0.953	0.999
F297	8	0.949	0.996
D291	8	0.946	0.991
N708	8	0.944	0.996

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.11e-05
Thyroid Carcinoma (TCGA)	unfavorable	0.000185
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000418

Disease associations

OMIM: gene MIM:603873 | disease phenotypes: MIM:617527

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies	Strong	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (MONDO:0060502)

Orphanet (1): PLAA-associated neurodevelopmental disorder (Orphanet:521426)

HPO phenotypes

showing 60 of 84 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000280	Coarse facial features
HP:0000319	Smooth philtrum
HP:0000338	Hypomimic face
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000490	Deeply set eye
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum
HP:0000851	Congenital hypothyroidism
HP:0000954	Single transverse palmar crease
HP:0000975	Hyperhidrosis
HP:0001007	Hirsutism
HP:0001162	Postaxial hand polydactyly
HP:0001187	Hyperextensibility of the finger joints
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001283	Bulbar palsy
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001561	Polyhydramnios
HP:0001830	Postaxial foot polydactyly
HP:0001838	Rocker bottom foot
HP:0001999	Abnormal facial shape
HP:0002015	Dysphagia
HP:0002033	Poor suck
HP:0002063	Rigidity
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002079	Hypoplasia of the corpus callosum
HP:0002093	Respiratory insufficiency
HP:0002104	Apnea
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002188	Delayed CNS myelination
HP:0002194	Delayed gross motor development
HP:0002197	Generalized-onset seizure
HP:0002267	Exaggerated startle response
HP:0002352	Leukoencephalopathy
HP:0002478	Progressive spastic quadriplegia
HP:0002483	Bulbar signs
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0002536	Abnormal cortical gyration
HP:0002553	Highly arched eyebrow
HP:0002808	Kyphosis
HP:0003196	Short nose
HP:0003487	Babinski sign

GWAS associations

5 associations:

Study	Trait	p-value
GCST007673_18	3-month functional outcome in ischaemic stroke (modified Rankin score)	8e-7
GCST000607_2	Schizophrenia	2e-6
GCST009391_1964	Metabolite levels	3e-6
GCST009391_2000	Metabolite levels	6e-6
GCST009391_850	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0010376	phosphatidylcholine 34:2 measurement
EFO:0010374	phosphatidylcholine 32:2 measurement
EFO:0010400	triacylglycerol 46:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6114 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

25 measured of 40 human assays (42 total across all organisms); most potent 25 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEBI:67559	KD	3.8 nM
CHEMBL4068569	IC50	36 nM
1-(3,4-dihydroxyphenyl)-2-(1-(4-methoxyphenyl)-1H-tetrazol-5-ylthio)ethanone	IC50	1130 nM
1-(3,4-dihydroxyphenyl)-2-(4,6-dimethylpyrimidin-2-ylthio)ethanone	IC50	1210 nM
CHEMBL5653589	KD	1440 nM
3-(2-(3,4-dihydroxyphenyl)-2-oxoethyl)-6,7-dimethoxyisobenzofuran-1(3H)-one	IC50	1830 nM
1-(3,4-dihydroxyphenyl)-2-(4-methyl-1H-pyrazol-1-yl)ethanone	IC50	2130 nM
2-(2-(3,4-dihydroxyphenyl)-2-oxoethylthio)-4-(methoxymethyl)-6-methylnicotinonitrile	IC50	2160 nM
1-(3,4-dihydroxyphenyl)-2-(2-methyl-1-imidazolyl)ethanone;hydrochloride	IC50	2370 nM
1-(3,4-dihydroxyphenyl)-2-(2-methyl-1-benzimidazolyl)ethanone;hydrochloride	IC50	2510 nM
1-(3,4-dihydroxyphenyl)-2-(2-ethyl-1-imidazolyl)ethanone;hydrochloride	IC50	3730 nM
1-(3,4-dihydroxyphenyl)-2-(4-methyl-5-phenyl-4H-1,2,4-triazol-3-ylthio)ethanone	IC50	4730 nM
1-[3,4-bis(oxidanyl)phenyl]-2-(4-bromanyl-2-methyl-imidazol-1-yl)ethanone;hydrochloride	IC50	4960 nM
1-(3,4-dihydroxyphenyl)-2-(4-methyl-1-imidazolyl)ethanone;hydrochloride	IC50	5810 nM
1-(3,4-dihydroxyphenyl)-2-(5,6-dimethyl-1-benzimidazolyl)ethanone;hydrochloride	IC50	5830 nM
MLS-0315849.0001	IC50	6200 nM
1-(3,4-dihydroxyphenyl)-2-(1,2,4-triazol-4-yl)ethanone;hydrochloride	IC50	13400 nM
2-(1-benzimidazolyl)-1-(3,4-dihydroxyphenyl)ethanone;hydrochloride	IC50	14800 nM
1-[3,4-bis(oxidanyl)phenyl]-2-(4-bromanylimidazol-1-yl)ethanone;hydrochloride	IC50	15800 nM
1-(3,4-dihydroxyphenyl)-2-(2-phenyl-1-imidazolyl)ethanone;hydrochloride	IC50	17200 nM
1-(3,4-dihydroxyphenyl)-2-(1-imidazolyl)ethanone;hydrochloride	IC50	18500 nM
1-(3,4-dihydroxyphenyl)-2-(isopropylamino)ethanone;hydrochloride	IC50	39300 nM
4-((4,6-dimethylpyrimidin-2-ylamino)methyl)benzene-1,2-diol	IC50	51200 nM
N-(3,4-dihydroxybenzyl)-4,5-dimethylfuran-2-carboxamide	IC50	52700 nM
cid_654283	EC50	65300 nM

ChEMBL bioactivities

21 potent at pChembl≥5 of 27 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	IC50	11	nM	CHEMBL1077979
7.44	IC50	36	nM	CHEMBL4068569
6.38	Kd	421.5	nM	CHEMBL5653589
6.38	ED50	421.5	nM	CHEMBL5653589
6.10	IC50	800	nM	CHEMBL608723
6.10	IC50	800	nM	CHEMBL607856
5.92	IC50	1200	nM	CHEMBL597055
5.70	IC50	2000	nM	CHEMBL254255
5.68	IC50	2100	nM	CHEMBL349641
5.66	IC50	2200	nM	CHEMBL598663
5.60	IC50	2500	nM	CHEMBL592869
5.57	IC50	2700	nM	CHEMBL610781
5.52	IC50	3000	nM	CHEMBL610508
5.48	IC50	3300	nM	CHEMBL589756
5.38	IC50	4200	nM	CHEMBL607856
5.31	IC50	4900	nM	CHEMBL597109
5.24	IC50	5800	nM	CHEMBL597027
5.24	IC50	5800	nM	CHEMBL602242
5.18	IC50	6600	nM	CHEMBL597055
5.17	IC50	6700	nM	CHEMBL609899
5.04	IC50	9100	nM	CHEMBL597837

PubChem BioAssay actives

20 with measured affinity, of 46 total; 18 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
(4S,6Z,9S,10S,12E)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	1469808: Inhibition of TNFalpha-PLAP (unknown origin)	ic50	0.0110	uM
(4S,6E,9S,10S,12E)-7-fluoro-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	1469808: Inhibition of TNFalpha-PLAP (unknown origin)	ic50	0.0360	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149022: Binding affinity to human PLAA incubated for 45 mins by Kinobead based pull down assay	kd	0.4215	uM
1-(3,4-dihydroxyphenyl)-2-(2-ethylimidazol-1-yl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	0.8000	uM
2-(benzimidazol-1-yl)-1-(3,4-dihydroxyphenyl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	0.8000	uM
1-(3,4-dihydroxyphenyl)-2-(2-methylbenzimidazol-1-yl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	1.2000	uM
1-(3,4-dihydroxyphenyl)-2-[1-(4-methoxyphenyl)tetrazol-5-yl]sulfanylethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	2.0000	uM
1-(3,4-dihydroxyphenyl)-2-imidazol-1-ylethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	2.1000	uM
2-[2-(3,4-dihydroxyphenyl)-2-oxoethyl]sulfanyl-4-(methoxymethyl)-6-methylpyridine-3-carbonitrile	459064: Inhibition of PLAP by analogous luminescence assay	ic50	2.2000	uM
1-(3,4-dihydroxyphenyl)-2-(4,6-dimethylpyrimidin-2-yl)sulfanylethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	2.5000	uM
1-(3,4-dihydroxyphenyl)-2-(4-methylpyrazol-1-yl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	2.7000	uM
3-[2-(3,4-dihydroxyphenyl)-2-oxoethyl]-6,7-dimethoxy-3H-2-benzofuran-1-one	459064: Inhibition of PLAP by analogous luminescence assay	ic50	3.0000	uM
1-(3,4-dihydroxyphenyl)-2-(2-methylimidazol-1-yl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	3.3000	uM
2-(4-bromo-2-methylimidazol-1-yl)-1-(3,4-dihydroxyphenyl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	4.9000	uM
1-(3,4-dihydroxyphenyl)-2-(5,6-dimethylbenzimidazol-1-yl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	5.8000	uM
1-(3,4-dihydroxyphenyl)-2-(4-methylimidazol-1-yl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	5.8000	uM
1-(3,4-dihydroxyphenyl)-2-[(4-methyl-5-phenyl-1,2,4-triazol-3-yl)sulfanyl]ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	6.7000	uM
2-(1H-benzimidazol-2-ylamino)-1-(3,4-dihydroxyphenyl)ethanone	459064: Inhibition of PLAP by analogous luminescence assay	ic50	9.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
afuresertib	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
salinomycin	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Catechin	decreases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Estradiol	increases expression	1
Furaldehyde	affects cotreatment, decreases expression, affects localization, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054562	Binding	Inhibition of PLAP by luminescent assay	Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2B3	Abcam HeLa PLAA KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLAA across ~30M SureChEMBL compounds — explore on Sugi Predict.