SERPINA2

Summary

SERPINA2 (serpin family A member 2 (gene/pseudogene), HGNC:8985) is a protein-coding gene on chromosome 14q32.13, encoding Alpha-1-antitrypsin-related protein (P20848). Putative serine protease inhibitor.

This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. The encoded intracellular glycoprotein is localized at the endoplasmic reticulum. This gene is a polymorphic pseudogene, with the non-functional allele being predominant in some populations. Some individuals, as represented by the reference genome allele, contain a 2kb coding region deletion and a start code mutation.

Source: NCBI Gene 390502 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8985
Approved symbol	SERPINA2
Name	serpin family A member 2 (gene/pseudogene)
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	ATR, ARGS
Ensembl gene	ENSG00000258597
Ensembl biotype	protein_coding
OMIM	107410
Entrez	390502

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding_LoF

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

ENST00000553483

RefSeq mRNA: 0

Canonical transcript exons

ENST00000553483 — 2 exons

Exon	Start	End
ENSE00002522842	94366044	94366698
ENSE00003726472	94364316	94364588

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 79.37.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, granulocyte, liver, blood, lobe of liver.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SERPINA2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.6e-06	-0.28	14:94372403:A:G

Top tissues by expression

showing 100 of 117 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.37	silver quality
granulocyte	CL:0000094	55.62	gold quality
liver	UBERON:0002107	46.15	gold quality
blood	UBERON:0000178	44.53	gold quality
right lobe of liver	UBERON:0001114	38.70	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
leukocyte	CL:0000738	36.31	silver quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.93	gold quality
monocyte	CL:0000576	34.71	silver quality
vermiform appendix	UBERON:0001154	34.17	gold quality
bone marrow	UBERON:0002371	33.24	gold quality
muscle tissue	UBERON:0002385	32.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
islet of Langerhans	UBERON:0000006	31.71	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	29.46	silver quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
placenta	UBERON:0001987	27.59	gold quality
lymph node	UBERON:0000029	27.57	gold quality
left uterine tube	UBERON:0001303	27.32	silver quality
tonsil	UBERON:0002372	27.05	gold quality
urinary bladder	UBERON:0001255	26.84	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
right lung	UBERON:0002167	25.18	gold quality
muscle of leg	UBERON:0001383	24.89	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
frontal cortex	UBERON:0001870	24.16	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
upper lobe of left lung	UBERON:0008952	23.87	silver quality
gastrocnemius	UBERON:0001388	23.68	gold quality
endometrium	UBERON:0001295	23.24	gold quality
calcaneal tendon	UBERON:0003701	23.08	gold quality
spleen	UBERON:0002106	22.28	gold quality
myometrium	UBERON:0001296	22.23	gold quality
smooth muscle tissue	UBERON:0001135	22.15	gold quality
lower esophagus mucosa	UBERON:0035834	22.15	gold quality
multicellular organism	UBERON:0000468	22.14	gold quality
heart left ventricle	UBERON:0002084	21.98	gold quality
uterine cervix	UBERON:0000002	21.86	gold quality
small intestine	UBERON:0002108	21.79	gold quality
body of pancreas	UBERON:0001150	21.36	gold quality
stomach	UBERON:0000945	21.27	gold quality
heart	UBERON:0000948	21.23	gold quality
popliteal artery	UBERON:0002250	21.05	gold quality
tibial artery	UBERON:0007610	21.05	gold quality
body of stomach	UBERON:0001161	20.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	20.37	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
adrenal gland	UBERON:0002369	20.25	gold quality
ectocervix	UBERON:0012249	20.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	20.20	gold quality
esophagus	UBERON:0001043	20.17	gold quality
esophagus mucosa	UBERON:0002469	19.99	gold quality
mucosa of transverse colon	UBERON:0004991	19.91	gold quality
thoracic aorta	UBERON:0001515	19.84	gold quality
ascending aorta	UBERON:0001496	19.73	gold quality
right atrium auricular region	UBERON:0006631	19.63	gold quality
lower esophagus	UBERON:0013473	19.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	19.57	gold quality
substantia nigra	UBERON:0002038	19.53	gold quality
omental fat pad	UBERON:0010414	19.41	gold quality
right coronary artery	UBERON:0001625	19.38	gold quality
cerebellum	UBERON:0002037	19.38	gold quality
adipose tissue	UBERON:0001013	19.35	gold quality
putamen	UBERON:0001874	19.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	19.27	gold quality
cerebellar cortex	UBERON:0002129	19.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	19.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	19.22	gold quality
ovary	UBERON:0000992	19.21	gold quality
left adrenal gland	UBERON:0001234	19.17	gold quality
Ammon’s horn	UBERON:0001954	19.12	gold quality
cerebellar hemisphere	UBERON:0002245	19.03	gold quality
left coronary artery	UBERON:0001626	19.00	gold quality
thoracic mammary gland	UBERON:0005200	18.99	gold quality
temporal lobe	UBERON:0001871	18.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	18.97	gold quality
left adrenal gland cortex	UBERON:0035825	18.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	18.85	gold quality
fundus of stomach	UBERON:0001160	18.84	gold quality
amygdala	UBERON:0001876	18.76	gold quality
transverse colon	UBERON:0001157	18.72	gold quality
prostate gland	UBERON:0002367	18.69	gold quality
right adrenal gland cortex	UBERON:0035827	18.68	gold quality
rectum	UBERON:0001052	18.65	gold quality
right adrenal gland	UBERON:0001233	18.63	gold quality
right ovary	UBERON:0002118	18.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	18.43	gold quality
descending thoracic aorta	UBERON:0002345	18.35	gold quality
mucosa of stomach	UBERON:0001199	18.29	gold quality
adrenal tissue	UBERON:0018303	18.25	gold quality
left ovary	UBERON:0002119	18.10	gold quality
skin of leg	UBERON:0001511	17.88	gold quality
thyroid gland	UBERON:0002046	17.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

HPA expression

RNA tissue specificity: Tissue enriched

29 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebellum	tissue	206.0
Epididymis	tissue	101.0
Medulla oblongata	tissue	34.2
Periaqueductal gray	tissue	30.5
Spinal cord	tissue	23.6
Pons	tissue	19.1
Midbrain	tissue	16.4
Thalamus	tissue	9.7
Superior colliculi	tissue	9.7
Substantia nigra	tissue	7.3
Hypothalamus	tissue	7.1
Olfactory bulb	tissue	6.6
Corpus callosum	tissue	5.1
Cerebral cortex	tissue	5.0
Insular cortex	tissue	5.0
Basal ganglia	tissue	4.7
Retrosplenial and cingulate cortex	tissue	4.7
Temporal cortex	tissue	4.7
Amygdala	tissue	4.6
Hippocampal formation	tissue	4.6
Ventral forebrain	tissue	4.6
Entorhinal cortex	tissue	4.5
Retrosplenial cortex	tissue	4.5
Putamen	tissue	4.4
Septum	tissue	4.3
Prefrontal cortex	tissue	4.2
Occipital cortex	tissue	4.1
Somatosensory cortex	tissue	3.9
Motor cortex	tissue	3.7

Brain sub-regions (HPA Brain Atlas): detected in 7; highest nTPM — Ventral spinal cord (23.6), Dorsal spinal cord (14.6), White matter (5.1), Ventral hippocampus (4.6), Dorsal hippocampus (4.5).

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Study found that a common haplotype in Africa had a 2-kb deletion in the SERPINA2 gene is associated with remarkable long-range homozygozity as if it was quickly driven to high frequency by natural selection acting on an advantageous variant. (PMID:17135331)
• Specific features of SERPINA2 include the absence of insoluble aggregates and the insignificant response to cell stress, suggesting that it is a non-polymerogenic protein with divergent activity of SERPINA1. (PMID:23826168)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpina1f	ENSMUSG00000021081
rattus_norvegicus	Serpina1f	ENSRNOG00000037762
rattus_norvegicus	Serpina1fl2	ENSRNOG00000064752

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915598) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal lens morphology	1
increased circulating total protein level	1

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
Pan troglodytes	P61640	99.8%	Diamond
Bos taurus	A2I7N0	99.5%	Diamond
Pongo abelii	Q5RCR2	98.4%	Diamond
Tamias sibiricus	O54759	98.1%	Diamond
Papio anubis	P01010	97.0%	Diamond
Chlorocebus aethiops	O00394	96.7%	Diamond
Ovis aries	P50450	96.1%	Diamond
Cavia porcellus	P22324	94.0%	Diamond
Sus scrofa	Q9TT35	89.8%	Diamond
Mus saxicola	Q63969	87.1%	Diamond
Saimiri sciureus	P50451	86.2%	Diamond
Mus caroli	P26595	86.1%	Diamond
Ictidomys tridecemlineatus	O54761	81.1%	Diamond
Callosciurus caniceps	O54763	80.8%	Diamond
Ursus arctos	B2D1U1	76.5%	Diamond
Mesocricetus auratus	P97277	76.3%	Diamond
Meriones unguiculatus	Q64118	76.3%	Diamond
Apodemus sylvaticus	Q60396	75.5%	Diamond
Equus caballus	P38029	74.1%	Diamond
Oryctolagus cuniculus	P23775	71.0%	Diamond
Didelphis virginiana	Q03044	59.8%	Diamond
Cyprinus carpio	P32759	43.6%	Diamond
Xenopus laevis	Q00387	42.0%	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
SERPINA10	protein-coding	51156
SERPINA1	protein-coding	5265
SERPINA6	protein-coding	866
SERPINA11	protein-coding	256394
PPP4R4	protein-coding	57718
SERPINA9	protein-coding	327657

Protein

Protein identifiers

Alpha-1-antitrypsin-related protein — P20848 (reviewed: P20848)

Alternative names: Protease inhibitor 1-like, Serpin A2

All UniProt accessions (1): A0A0U1RQB8

UniProt curated annotations — full annotation on UniProt →

Function. Putative serine protease inhibitor.

Subunit / interactions. Interacts with CANX and PDIA3.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Expressed in the liver, leukocytes and testis. Also detected in brain, colon, uterus, esophagus, spleen, trachea, kidney and lung.

Post-translational modifications. Glycosylated.

Domain organisation. The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

Polymorphism. The SERPINA2 gene is highly polymorphic. Deletions, frameshift mutations and a critical start codon variation (ATG->ATA, dbSNP:rs1956172) have been found in some populations. Population studies suggest that a pseudogenization process may be ongoing in humans. 3 potentially functional alleles, V1, V2 and V3, have been described in the literature. The sequence shown in this entry is that of allele V2.

Similarity. Belongs to the serpin family.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (15 total): sequence conflict 6, glycosylation site 4, sequence variant 2, signal peptide 1, chain 1, site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20848-F1	84.60	0.67

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at transcript level

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 (1)

Position	Role
385–386	reactive bond

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	56, 110, 148, 274

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: 522 (showing top): PID_FANCONI_PATHWAY, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_POSITIVE_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_MEMBRANE_DISASSEMBLY

GO Molecular Function (1): serine-type endopeptidase inhibitor activity (GO:0004867)

GO Cellular Component (1): endoplasmic reticulum (GO:0005783)

GO top-level categories

5 GO namespaces:

Category	Terms
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 3 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
endoplasmic reticulum	CC	direct assay

Disease & clinical

Genetic variants

Variant evidence for SERPINA2: 3 GWAS associations.

ClinVar

No ClinVar records for this gene.

Disease associations

OMIM: gene MIM:107410 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST007615_64	C-reactive protein levels	2e-10
GCST005194_65	Coronary artery disease	5e-10
GCST005195_2	Coronary artery disease	8e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4879431 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,341 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3989870	BERZOSERTIB	2	1,341

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
3-[3-[4-[dideuterio(methylamino)methyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine	IC50	0.2 nM
CHEMBL5596626	IC50	20 nM
CHEMBL4860779	IC50	141 nM
CHEMBL4875626	IC50	270 nM
CHEMBL4851439	IC50	394 nM
CHEMBL4849035	IC50	551 nM
CHEMBL4871998	IC50	790 nM
CHEMBL4850640	IC50	907 nM
CHEMBL4860129	IC50	1320 nM
CHEMBL4873263	IC50	2160 nM
CHEMBL4867528	IC50	4920 nM

ChEMBL bioactivities

9 potent at pChembl≥5 of 9 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	BERZOSERTIB
7.70	IC50	20	nM	CHEMBL5596626
6.19	IC50	641	nM	CHEMBL4875626
5.63	IC50	2360	nM	CHEMBL4851439
5.54	IC50	2890	nM	CHEMBL4860779
5.39	IC50	4080	nM	CHEMBL4849035
5.22	IC50	6000	nM	CHEMBL4850640
5.21	IC50	6160	nM	CHEMBL4871998
5.08	IC50	8300	nM	CHEMBL4873263

PubChem BioAssay actives

9 with measured affinity, of 13 total; 9 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
3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1876294: Binding affinity to ATR (unknown origin)	ic50	0.0002	uM
2-methyl-2-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)propanenitrile	2122174: Inhibition of ATR (unknown origin)	ic50	0.0200	uM
1-(cyclohexen-1-yl)-8-[5-(difluoromethyl)-3-pyridinyl]-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	0.6410	uM
8-[5-(difluoromethyl)-3-pyridinyl]-1-(2,3,6,7-tetrahydrooxepin-4-yl)-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	2.3600	uM
1-(cyclohepten-1-yl)-8-[5-(difluoromethyl)-3-pyridinyl]-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	2.8900	uM
8-[5-(difluoromethyl)-3-pyridinyl]-1-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	4.0800	uM
8-[5-(difluoromethyl)-3-pyridinyl]-1-(4-methoxycyclohexyl)-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	6.0000	uM
1-[(1S,5R)-6-bicyclo[3.1.0]hexanyl]-8-[5-(difluoromethyl)-3-pyridinyl]-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	6.1600	uM
8-[5-(difluoromethyl)-3-pyridinyl]-1-[(1R,5S)-3-oxabicyclo[3.1.0]hexan-6-yl]-[1,2,4]triazolo[4,3-a]quinoxaline	1779784: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	ic50	8.3000	uM

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
abrine	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Dust	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	1
Ozone	increases abundance, increases expression	1

ChEMBL screening assays

5 unique, capped per target: 3 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4839371	Binding	Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay	BAY-8400: A Novel Potent and Selective DNA-PK Inhibitor which Shows Synergistic Efficacy in Combination with Targeted Alpha Therapies. — *J Med Chem*
CHEMBL5159408	Functional	In vivo inhibition of ATR in human LoVo cells xenografted in NOD/SCID mouse assessed as inhibition of ATR phosphorylation at 50 to 100 mg/kg, po administered twice a day for 30 days by Western blot analysis	Discovery of a potent and highly selective inhibitor of ataxia telangiectasia mutated and Rad3-Related (ATR) kinase: Structural activity relationship and antitumor activity both in vitro and in vivo. — *Eur J Med Chem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SERPINA2 across ~30M SureChEMBL compounds — explore on Sugi Predict.