ACVR2A

Summary

ACVR2A (activin A receptor type 2A, HGNC:173) is a protein-coding gene on chromosome 2q22.3-q23.1, encoding Activin receptor type-2A (P27037). On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.

This gene encodes a receptor that mediates the functions of activins, which are members of the transforming growth factor-beta (TGF-beta) superfamily involved in diverse biological processes. The encoded protein is a transmembrane serine-threonine kinase receptor which mediates signaling by forming heterodimeric complexes with various combinations of type I and type II receptors and ligands in a cell-specific manner. The encoded type II receptor is primarily involved in ligand-binding and includes an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic serine-threonine kinase domain. This gene may be associated with susceptibility to preeclampsia, a pregnancy-related disease which can result in maternal and fetal morbidity and mortality. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 92 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 81 total — 21 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 7 cancer types
• MANE Select transcript: NM_001616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:173
Approved symbol	ACVR2A
Name	activin A receptor type 2A
Location	2q22.3-q23.1
Locus type	gene with protein product
Status	Approved
Aliases	ACTRII
Ensembl gene	ENSG00000121989
Ensembl biotype	protein_coding
OMIM	102581
Entrez	92

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000241416, ENST00000404590, ENST00000462659, ENST00000465329, ENST00000487959, ENST00000495775, ENST00000535787, ENST00000873789, ENST00000935938, ENST00000943648, ENST00000943649, ENST00000943650, ENST00000943651, ENST00000943652

RefSeq mRNA: 3 — MANE Select: NM_001616 NM_001278579, NM_001278580, NM_001616

CCDS: CCDS33301, CCDS63030

Canonical transcript exons

ENST00000241416 — 11 exons

Exon	Start	End
ENSE00000777569	147915191	147915334
ENSE00000777570	147917283	147917426
ENSE00000777571	147918447	147918592
ENSE00000777572	147920230	147920344
ENSE00000777573	147922973	147923111
ENSE00000777574	147926031	147926161
ENSE00001153978	147927080	147930822
ENSE00001842428	147845029	147845207
ENSE00003487221	147899744	147899898
ENSE00003565022	147896301	147896508
ENSE00003675365	147899458	147899567

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 91.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5726 / max 2117.4752, expressed in 1724 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22943	7.8208	1426
22939	7.5630	1659
22942	0.9052	475
22940	0.1559	64
22941	0.1277	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.79	gold quality
cervix squamous epithelium	UBERON:0006922	91.51	silver quality
cortical plate	UBERON:0005343	91.48	gold quality
hair follicle	UBERON:0002073	91.38	silver quality
oocyte	CL:0000023	91.16	gold quality
upper leg skin	UBERON:0004262	90.84	gold quality
oviduct epithelium	UBERON:0004804	90.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.63	gold quality
skin of abdomen	UBERON:0001416	90.38	gold quality
mammary duct	UBERON:0001765	90.37	gold quality
epithelium of mammary gland	UBERON:0003244	90.30	gold quality
diaphragm	UBERON:0001103	90.28	gold quality
type B pancreatic cell	CL:0000169	90.15	gold quality
zone of skin	UBERON:0000014	89.95	gold quality
skin of leg	UBERON:0001511	89.94	gold quality
olfactory bulb	UBERON:0002264	89.88	gold quality
ganglionic eminence	UBERON:0004023	89.69	gold quality
embryo	UBERON:0000922	89.15	gold quality
tendon	UBERON:0000043	88.30	gold quality
calcaneal tendon	UBERON:0003701	88.21	gold quality
jejunal mucosa	UBERON:0000399	88.15	gold quality
amniotic fluid	UBERON:0000173	87.97	gold quality
tongue squamous epithelium	UBERON:0006919	87.83	silver quality
skin of hip	UBERON:0001554	87.43	gold quality
squamous epithelium	UBERON:0006914	87.41	gold quality
epithelium of esophagus	UBERON:0001976	87.40	gold quality
endothelial cell	CL:0000115	87.30	gold quality
cervix epithelium	UBERON:0004801	87.09	gold quality
epithelium of nasopharynx	UBERON:0001951	87.08	gold quality
esophagus squamous epithelium	UBERON:0006920	86.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	2218.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HAMP	Activation

miRNA regulators (miRDB)

227 targeting ACVR2A, 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-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Literature-anchored findings (GeneRIF, showing 40)

• distribution in gestational tissues across human pregnancy and during labour (PMID:11969340)
• crystal structure of BMP7 in complex with the extracellular domain (ECD) of the activin type II receptor (PMID:12667445)
• Activin type II receptor gene (ACTRII) is probably involved in both non-microsattelite unstable and microsattelite-unstable colorectal carcinogenesis, but more frequently in the latter subgroup. (PMID:14691305)
• Data indicate that activin A and activin receptors IIA and IIB may be involved in the regulation of germ cell proliferation in the human ovary during the period leading up to primordial follicle formation. (PMID:14738881)
• Mutations highly frequent in microsatellite unstable(MSI-H) colon cancers and cause loss of ACVR2, indicating biallelic gene nactivation. Loss of activin signaling through mutation of ACVR2 may have role in genesis of MSI-H colorectal cancer. (PMID:14988818)
• demonstrates that truncating mutations of the ACVR2 gene result in a significant reduction in activin mediated cell signaling. Inactivation of ACVR2 is a common event in prostate cancer and may play an important role in the development of prostate cancer (PMID:16337854)
• structure of the ternary complex representing the signaling competent complex of BMP-2 bound to the entire extracellular domains of both its type I receptor, BMPR-Ia, & its type II receptor, ActRII, at a resolution of 2.2 angstroms (PMID:16672363)
• Activin is growth suppressive and enhances migration in colon cancer. (PMID:17258738)
• RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal (PMID:17472960)
• Inhibin/activin BA subunit, follistatin, and activin receptor proteins and mRNAs are present in the human fetal palate. (PMID:18001154)
• Populations with different ancestors (Iceland/Norway-Australia/New Zealand) demonstrate a common maternal pre-eclampsia susceptibility locus on chromosome 2q22-23, may suggests a general role of this locus, and possibly the ACVR2A gene, in pre-eclampsia. (PMID:18781190)
• The -1 bp frameshift mutation rates of TGFBR2 and ACVR2 microsatellite sequences are dependent upon the human DNA Mismatch (PMID:18941508)
• It remains unclear what role, if any, ACVR2A polymorphisms play in pre-eclampsia risk, at least in these Australian families. (PMID:19126782)
• ActRII signaling is required for prostatic cancer cell and neuroblastoma cell viability, with ActRII mediating cell fate via the regulation of cell adhesion (PMID:19308291)
• The four most frequently mutated genes in colorectal cancers with microsatellite instability were ACVR2 (92%), TAF1B (84%), ASTE1/HT001 (80%) and TGFBR2 (77%). (PMID:19503063)
• Of 51 microsatellite stable colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression. (PMID:20011542)
• Mutation in activin type II receptor is associated with colorectal cancer. (PMID:20197483)
• Exonic selectivity for frameshift mutation within ACVR2 is specifically controlled by individual nucleotides flanking each coding ACVR2 microsatellite. (PMID:22001236)
• Activin type IIA receptors are clearly demonstrable throughout the adult human hypothalamus and basal forebrain. (PMID:22296042)
• This is the first report on the function of miR-195 in human placental trophoblast cells which reveals an invasion-promoting effect of the small RNA via repressing ActRIIA. (PMID:22723898)
• ACVR2A showed statistically significant differential dose-expression relationship. (PMID:22848350)
• ACVR2A interaction with Nodal and ADMP regulates head development from the ‘organizer’, a restricted group of cells in the embryo. (PMID:22949641)
• ACVR2A was identified as a subnetwork component in functional association network analysis. (PMID:23263486)
• For ACVR2A SNPs (rs10497025, rs1128919, rs13430086), no statistically significant difference was found between preeclampsia and control groups in terms of genotype and allele frequencies. (PMID:23633461)
• The gene ACVR2A was associated with the more severe early onset preeclampsia. (PMID:25499008)
• Data suggest that an SNP in promoter region of ACVR2A (rs1424954, the pre-eclampsia susceptibility allele) down-regulates 1) expression of ACVR2A in trophoblasts and 2) signal transduction in response to excess activin-A (as seen in pre-eclampsia). (PMID:25659497)
• Activin A inhibited signaling by BMP-6 and BMP-9 by competing for type 2 receptors ACVR2A and ACVR2B. (PMID:26047946)
• Adenomyotic tissues express high levels of myostatin, follistatin, and activin type II receptors. (PMID:26086422)
• Data suggest ALK1 and ACVR2A/ACVR2B, acting as BMP9 co-receptors, rearrange pro-domains of BMP9–pro-domain dimer complex leading to displacement of pro-domains after receptor binding, release of mature non-dimer BPM9, and activation of signaling. (PMID:26677222)
• TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence.( (PMID:27696331)
• This locus harbors an evolutionary conserved gene-desert region with non-coding intergenic sequences likely involved in regulation of protein-coding flanking genes ZEB2 and ACVR2A. This region is intensively studied for mutations causing severe developmental/genetic disorders. Our analyses indicate a promising target region for interventions aimed to reduce risks of many major human diseases and mortality. (PMID:27832070)
• Altered decidual ACVR2A expression impairs the ability of stromal cells to properly decidualise and regulate trophoblast function at the maternalfetal interface, which may result in abnormal placentation that can lead to poor pregnancy outcomes such as pre-eclampsia. (PMID:29203340)
• A case-control study targeting next generation sequencing of ACVR2A gene by Ion Torrent Personal Genome Sequencing suggested that some variants in the ACVR2A gene are associated with pre-eclampsia. (PMID:29506428)
• Results showed no association between genotypes and preeclampsia for polymorphisms rs5186, rs4606 in 3’UTR of genes ACVR2A, AGTR1 and RGS2 in women with preeclampsia (PMID:29593124)
• The multifactor dimensionality reduction algorithm identified an interaction between age, body mass index and ACVR2A rs1014064, indicating that context among genetic variants and demographic/clinical factors may be crucial to understanding the pathogenesis of preeclampsia among Filipino women. (PMID:30621627)
• Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. (PMID:31273315)
• the structure of an activin class member, GDF11, in complex with the type II receptor ActRIIB and the type I receptor Alk5, is reported. (PMID:31315975)
• Association between ACVR2A gene polymorphisms and risk of hypertensive disorders of pregnancy in the northern Chinese population. (PMID:31790936)
• Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer. (PMID:33420656)
• Activin A/ACVR2A axis inhibits epithelial-to-mesenchymal transition in colon cancer by activating SMAD2. (PMID:37378449)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	acvr2aa	ENSDARG00000011188
danio_rerio	acvr2ab	ENSDARG00000104700
mus_musculus	Acvr2a	ENSMUSG00000052155
rattus_norvegicus	Acvr2a	ENSRNOG00000065897
drosophila_melanogaster	tkv	FBGN0003716
drosophila_melanogaster	babo	FBGN0011300
caenorhabditis_elegans		WBGENE00000897
caenorhabditis_elegans		WBGENE00004860

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Activin receptor type-2A — P27037 (reviewed: P27037)

Alternative names: Activin receptor type IIA

All UniProt accessions (1): P27037

UniProt curated annotations — full annotation on UniProt →

Function. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6.

Subunit / interactions. Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3. Interacts with MAGI2/ARIP1. Interacts with type I receptor ACVR1. Interacts with BMP7. Interacts with TSC22D1/TSC-22. Interacts with activin A/INHBA.

Subcellular location. Cell membrane.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P27037-1	1	yes
P27037-2	2

RefSeq proteins (3): NP_001265508, NP_001265509, NP_001607* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00069, PF01064

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) (RHEA:18673)
• L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) (RHEA:44880)

UniProt features (58 total): strand 18, helix 16, disulfide bond 5, sequence conflict 4, sequence variant 3, glycosylation site 2, topological domain 2, binding site 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, domain 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3SOC	X-RAY DIFFRACTION	1.95
3Q4T	X-RAY DIFFRACTION	1.96
4ASX	X-RAY DIFFRACTION	2.05
5NH3	X-RAY DIFFRACTION	2.35
7U5P	X-RAY DIFFRACTION	3.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27037-F1	84.20	0.57

Antibody-complex structures (SAbDab): 1 — 5NH3

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): 322 (proton acceptor)

Ligand- & substrate-binding residues (2): 198–206; 219

Disulfide bonds (5): 30–60, 50–78, 85–104, 91–103, 105–110

Glycosylation sites (2): 66, 43

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-1433617	Regulation of signaling by NODAL
R-HSA-1502540	Signaling by Activin
R-HSA-201451	Signaling by BMP
R-HSA-9839406	TGFBR3 regulates activin signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 476 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, YAATNRNNNYNATT_UNKNOWN, ACTACCT_MIR196A_MIR196B, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_BEHAVIOR, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, ATACCTC_MIR202

GO Biological Process (30): osteoblast differentiation (GO:0001649), gastrulation with mouth forming second (GO:0001702), positive regulation of protein phosphorylation (GO:0001934), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), spermatogenesis (GO:0007283), determination of left/right symmetry (GO:0007368), pattern specification process (GO:0007389), mesoderm development (GO:0007498), anterior/posterior pattern specification (GO:0009952), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), activin receptor signaling pathway (GO:0032924), positive regulation of activin receptor signaling pathway (GO:0032927), odontogenesis of dentin-containing tooth (GO:0042475), sperm ejaculation (GO:0042713), penile erection (GO:0043084), regulation of nitric oxide biosynthetic process (GO:0045428), positive regulation of erythrocyte differentiation (GO:0045648), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic skeletal system development (GO:0048706), Sertoli cell proliferation (GO:0060011), positive regulation of SMAD protein signal transduction (GO:0060391), cellular response to growth factor stimulus (GO:0071363), cellular response to BMP stimulus (GO:0071773), protein phosphorylation (GO:0006468), male gonad development (GO:0008584), regulation of signal transduction (GO:0009966), negative regulation of ossification (GO:0030279), developmental process (GO:0032502)

GO Molecular Function (19): protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), ATP binding (GO:0005524), coreceptor activity (GO:0015026), activin receptor activity, type I (GO:0016361), activin receptor activity, type II (GO:0016362), activin receptor activity (GO:0017002), growth factor binding (GO:0019838), PDZ domain binding (GO:0030165), inhibin binding (GO:0034711), identical protein binding (GO:0042802), metal ion binding (GO:0046872), activin binding (GO:0048185), BMP receptor activity (GO:0098821), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), inhibin-betaglycan-ActRII complex (GO:0034673), signaling receptor complex (GO:0043235), activin receptor complex (GO:0048179), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by TGFB family members	3
Developmental Biology	1
Signaling by NODAL	1
Signaling by TGFBR3	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
cellular anatomical structure	3
transforming growth factor beta receptor superfamily signaling pathway	2
activin receptor signaling pathway	2
multicellular organismal reproductive process	2
activin receptor activity	2
transmembrane receptor protein serine/threonine kinase activity	2
ossification	1
cell differentiation	1
gastrulation	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
enzyme-linked receptor protein signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
determination of bilateral symmetry	1
left/right pattern formation	1
multicellular organism development	1
multicellular organismal process	1
tissue development	1
regionalization	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
cellular response to BMP stimulus	1
regulation of activin receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
odontogenesis	1
insemination	1
copulation	1
nitric oxide biosynthetic process	1
regulation of biosynthetic process	1
regulation of nitric oxide metabolic process	1
erythrocyte differentiation	1
positive regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
osteoblast differentiation	1

Protein interactions and networks

STRING

2342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACVR2A	MSTN	O14793	998
ACVR2A	GDF11	O95390	995
ACVR2A	BMP7	P18075	993
ACVR2A	ACVR1B	P36896	988
ACVR2A	ACVR1	Q04771	988
ACVR2A	BMP6	P22004	986
ACVR2A	ACVR2B	Q13705	981
ACVR2A	INHBA	P08476	980
ACVR2A	GDF2	Q9UK05	970
ACVR2A	BMP4	P12644	963
ACVR2A	ACVRL1	P37023	959
ACVR2A	ACVR1C	Q8NER5	953
ACVR2A	CRIPTO	P13385	938
ACVR2A	TGFBR1	P36897	928
ACVR2A	BMPR2	Q13873	928

IntAct

201 interactions, top by confidence:

A	B	Type	Score
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
MAST2	ACVR2A	psi-mi:“MI:0407”(direct interaction)	0.610
ACVR2A	SNX27	psi-mi:“MI:0407”(direct interaction)	0.610
ACVR2A	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.610
ACVR2A	DLG4	psi-mi:“MI:0407”(direct interaction)	0.610
ACVR2A	MAST2	psi-mi:“MI:0407”(direct interaction)	0.610
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
DAAM2	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
Magi2	ACVR2A	psi-mi:“MI:0915”(physical association)	0.510
ACVR2A	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (130): ACVR2A (Affinity Capture-Western), ACVR2A (Affinity Capture-Western), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), DAXX (Two-hybrid), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ACVR2A (Affinity Capture-MS)

ESM2 similar proteins: A4Q9F4, E1B8U2, G3X9X1, O15519, O43353, O94888, O95267, P00534, P00535, P27037, P33497, P34925, P37173, P38438, P58801, Q01887, Q14094, Q2TBA3, Q3LAC4, Q3SZJ2, Q3UGM2, Q4R8W3, Q59H18, Q5JSP0, Q5R5T1, Q5RD56, Q5REY7, Q60769, Q62312, Q69ZK0, Q6P5G6, Q6P9L4, Q6QNK2, Q6ZR37, Q6ZWH5, Q70CQ1, Q70Z35, Q7TQP6, Q8C0Q9, Q8K4B2

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TDGF1	down-regulates	ACVR2A	binding
INHBA	“up-regulates activity”	ACVR2A	binding
ACVR2A	“up-regulates activity”	SMAD2	phosphorylation
ACVR2A	up-regulates	ACVR1	binding
BMP7	up-regulates	ACVR2A	binding
ACVR2A	up-regulates	ACVR1B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 188 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Long-term potentiation	5	20.5×	1e-03
Assembly and cell surface presentation of NMDA receptors	6	13.1×	1e-03
Neurexins and neuroligins	7	11.9×	1e-03
Protein-protein interactions at synapses	5	11.4×	3e-03
RND3 GTPase cycle	5	11.2×	3e-03
Regulation of insulin secretion	5	9.5×	6e-03
RHOJ GTPase cycle	5	8.6×	8e-03
RHOB GTPase cycle	6	8.0×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	34.2×	2e-10
protein localization to synapse	5	22.5×	4e-04
receptor clustering	6	22.0×	1e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	6	17.5×	2e-04
establishment of cell polarity	5	11.3×	7e-03
cell-cell adhesion	11	6.6×	2e-04
chemical synaptic transmission	10	4.5×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 7 cancer types — COADREAD, CSCC, HCC, PAAD, PRAD, STAD, UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	2
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1341063	GRCh37/hg19 2q22.2-23.3(chr2:142409401-152680804)x3	Pathogenic
152517	GRCh38/hg38 2q22.3-23.2(chr2:145471053-149582570)x1	Pathogenic
1526906	GRCh37/hg19 2q22.2-23.3(chr2:143258712-152867819)	Pathogenic
1526908	GRCh37/hg19 2q22.3-23.1(chr2:146803587-149568729)	Pathogenic
153625	GRCh38/hg38 2q22.3-23.1(chr2:147732899-148156266)x1	Pathogenic
154515	GRCh38/hg38 2q22.3-24.1(chr2:146324191-156219125)x3	Pathogenic
2684742	GRCh37/hg19 2q22.3-23.3(chr2:148406827-152954124)x1	Pathogenic
3062637	GRCh37/hg19 2q22.3-23.1(chr2:148646132-148829749)x1	Pathogenic
403686	Single allele	Pathogenic
403687	Single allele	Pathogenic
403688	Single allele	Pathogenic
403689	Single allele	Pathogenic
403690	Single allele	Pathogenic
417820	Single allele	Pathogenic
417821	Single allele	Pathogenic
442694	GRCh37/hg19 2q22.3-23.3(chr2:146913477-151531586)x1	Pathogenic
60212	GRCh38/hg38 2q22.2-22.3(chr2:141666537-147845662)x1	Pathogenic
60217	GRCh38/hg38 2q22.3-23.3(chr2:147590324-153496674)x1	Pathogenic
814314	GRCh37/hg19 2q22.3-24.1(chr2:147173792-158346266)x1	Pathogenic
814315	GRCh37/hg19 2q22.3-23.1(chr2:148646132-148959158)x1	Pathogenic
980593	GRCh37/hg19 2q22.3-23.1(chr2:148679076-148894267)x1	Pathogenic
150047	GRCh38/hg38 2q22.3-23.1(chr2:147680433-148220153)x1	Likely pathogenic
57146	GRCh38/hg38 2q22.3-23.1(chr2:147713771-148177277)x1	Likely pathogenic

SpliceAI

2161 predictions. Top by Δscore:

Variant	Effect	Δscore
2:147896296:TATA:T	acceptor_loss	1.0000
2:147896298:TA:T	acceptor_loss	1.0000
2:147896299:A:AG	acceptor_gain	1.0000
2:147896299:A:G	acceptor_loss	1.0000
2:147896300:G:GG	acceptor_gain	1.0000
2:147896300:GGT:G	acceptor_gain	1.0000
2:147896347:T:TA	acceptor_gain	1.0000
2:147896351:A:AG	acceptor_gain	1.0000
2:147896351:AATTG:A	acceptor_gain	1.0000
2:147896504:GACAG:G	donor_gain	1.0000
2:147896505:ACAG:A	donor_gain	1.0000
2:147896506:CAG:C	donor_gain	1.0000
2:147896507:AG:A	donor_gain	1.0000
2:147896508:GG:G	donor_gain	1.0000
2:147896508:GGTA:G	donor_loss	1.0000
2:147896509:G:GG	donor_gain	1.0000
2:147896509:GTA:G	donor_loss	1.0000
2:147899566:GC:G	donor_gain	1.0000
2:147899742:A:AG	acceptor_gain	1.0000
2:147899743:G:GG	acceptor_gain	1.0000
2:147899743:GCC:G	acceptor_gain	1.0000
2:147899743:GCCA:G	acceptor_gain	1.0000
2:147901943:GC:G	donor_gain	1.0000
2:147917274:T:TA	acceptor_gain	1.0000
2:147917278:TCTA:T	acceptor_loss	1.0000
2:147917279:CTA:C	acceptor_loss	1.0000
2:147917281:A:AG	acceptor_gain	1.0000
2:147917281:AG:A	acceptor_gain	1.0000
2:147917282:G:A	acceptor_gain	1.0000
2:147917282:G:GT	acceptor_gain	1.0000

AlphaMissense

3392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:147896333:T:A	C30S	1.000
2:147896334:G:C	C30S	1.000
2:147896335:T:G	C30W	1.000
2:147896423:T:A	C60S	1.000
2:147896423:T:C	C60R	1.000
2:147896424:G:A	C60Y	1.000
2:147896424:G:C	C60S	1.000
2:147896425:T:G	C60W	1.000
2:147896477:T:A	C78S	1.000
2:147896477:T:C	C78R	1.000
2:147896478:G:C	C78S	1.000
2:147896482:G:C	W79C	1.000
2:147896482:G:T	W79C	1.000
2:147896498:T:C	C85R	1.000
2:147896499:G:A	C85Y	1.000
2:147896500:C:G	C85W	1.000
2:147899465:T:A	C91S	1.000
2:147899465:T:C	C91R	1.000
2:147899466:G:A	C91Y	1.000
2:147899466:G:C	C91S	1.000
2:147899467:T:G	C91W	1.000
2:147899501:T:C	C103R	1.000
2:147899502:G:A	C103Y	1.000
2:147899503:T:G	C103W	1.000
2:147899506:C:G	C104W	1.000
2:147899508:G:A	C105Y	1.000
2:147899509:T:G	C105W	1.000
2:147899522:T:A	C110S	1.000
2:147899523:G:C	C110S	1.000
2:147899524:T:G	C110W	1.000

dbSNP variants (sampled 300 via entrez): RS1000016806 (2:147878678 G>A), RS1000024278 (2:147882060 A>C,G), RS1000095860 (2:147853501 G>A,T), RS1000118055 (2:147906451 A>G), RS1000143568 (2:147869059 A>G), RS1000229483 (2:147906861 T>C), RS1000239672 (2:147916181 A>C,G), RS1000296371 (2:147847420 GACATGTTGGA>G), RS1000310328 (2:147860881 A>G), RS1000316081 (2:147854860 T>A,C), RS1000372553 (2:147848167 A>C,G), RS1000451715 (2:147904676 G>T), RS1000526459 (2:147886117 A>G), RS1000531294 (2:147853234 A>C), RS1000540646 (2:147848341 C>T)

Disease associations

OMIM: gene MIM:102581 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000635_18	Response to statin therapy	5.000000e-07
GCST001791_3	Urate levels	2.000000e-08
GCST003372_44	Glomerular filtration rate (creatinine)	1.000000e-06
GCST004071_7	Cerebrospinal T-tau levels	6.000000e-06
GCST004618_30	White blood cell count (basophil)	2.000000e-10
GCST004623_163	Neutrophil percentage of granulocytes	5.000000e-09
GCST004631_11	Basophil percentage of white cells	1.000000e-10
GCST004634_8	Basophil percentage of granulocytes	2.000000e-10
GCST006627_38	Diastolic blood pressure	1.000000e-11
GCST006924_15	Loneliness (MTAG)	2.000000e-08
GCST006943_28	Feeling miserable	2.000000e-08
GCST006948_15	Feeling nervous	5.000000e-08
GCST006951_34	Feeling hurt	3.000000e-10
GCST006952_16	Feeling tense	5.000000e-08
GCST007324_90	Adventurousness	5.000000e-09
GCST007325_228	General risk tolerance (MTAG)	4.000000e-09
GCST007687_1	Photic sneeze reflex	6.000000e-20
GCST007876_32	Estimated glomerular filtration rate	1.000000e-14
GCST007993_18	Asthma (adult onset)	2.000000e-10
GCST008403_35	Arterial stiffness index	4.000000e-06
GCST009959_9	Retinal detachment or retinal break	5.000000e-06
GCST009962_7	High myopia	1.000000e-08
GCST010002_399	Refractive error	2.000000e-10
GCST010242_60	HDL cholesterol levels	4.000000e-09
GCST010637_5	Urate levels	4.000000e-08
GCST010988_190	Adult body size	2.000000e-16
GCST90002379_27	Basophil count	3.000000e-10
GCST90002381_48	Eosinophil count	5.000000e-11
GCST90014033_15	Haemorrhoidal disease	5.000000e-08

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004760	t-tau measurement
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0006336	diastolic blood pressure
EFO:0007865	loneliness measurement
EFO:0009598	feeling miserable measurement
EFO:0009597	feeling nervous measurement
EFO:0009599	feeling emotionally hurt measurement
EFO:0009596	feeling tense measurement
EFO:0008579	risk-taking behaviour
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:1002011	adult onset asthma
EFO:0004517	arterial stiffness measurement
EFO:0010698	retinal break
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5616 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,058 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL5416410	DASATINIB	4	655
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type II receptor serine/threonine kinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
bimagrumab	Binding	9.36	pKd

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
BMS-354825	KD	27 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM

ChEMBL bioactivities

45 potent at pChembl≥5 of 46 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	Kd	10	nM	CHEMBL386051
7.75	Kd	18	nM	CHEMBL1241674
6.75	IC50	180	nM	CHEMBL4792978
6.72	IC50	190	nM	CHEMBL4741913
6.68	Kd	210	nM	DASATINIB
6.51	IC50	310	nM	CHEMBL4752199
6.50	Kd	320	nM	KW-2449
6.28	IC50	530	nM	CHEMBL4749011
6.20	IC50	630	nM	CHEMBL4744988
6.17	IC50	671	nM	CHEMBL6172244
6.16	IC50	700	nM	CHEMBL4741185
6.10	IC50	800	nM	CHEMBL4747422
6.07	IC50	860	nM	CHEMBL4744618
6.07	IC50	860	nM	CHEMBL5417444
6.02	IC50	960	nM	CHEMBL4763122
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	IC50	1100	nM	CHEMBL4795223
5.92	IC50	1200	nM	CHEMBL4750258
5.92	IC50	1200	nM	CHEMBL4798505
5.89	IC50	1300	nM	CHEMBL4783244
5.89	IC50	1300	nM	CHEMBL4779579
5.72	IC50	1900	nM	CHEMBL4779273
5.66	Kd	2200	nM	TAE-684
5.64	IC50	2300	nM	CHEMBL4758580
5.64	IC50	2300	nM	CHEMBL4791414
5.62	IC50	2370	nM	CHEMBL4283638
5.62	IC50	2400	nM	CHEMBL4787891
5.60	Kd	2500	nM	LESTAURTINIB
5.57	IC50	2700	nM	CHEMBL4764416
5.54	IC50	2900	nM	CHEMBL4782729
5.54	IC50	2900	nM	CHEMBL4764221
5.54	Kd	2900	nM	JNJ-7706621
5.52	IC50	3000	nM	CHEMBL4777071
5.52	IC50	3000	nM	CHEMBL4763627
5.52	IC50	3000	nM	CHEMBL4751832
5.51	Kd	3100	nM	ALVOCIDIB
5.42	IC50	3800	nM	CHEMBL4748097
5.39	IC50	4100	nM	CHEMBL4792464
5.28	IC50	5300	nM	CHEMBL4749061
5.05	Kd	8900	nM	STAUROSPORINE
5.03	IC50	9300	nM	CHEMBL513147

PubChem BioAssay actives

41 with measured affinity, of 234 total; 39 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
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624838: Binding constant for ACVR2A kinase domain	kd	0.0100	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624838: Binding constant for ACVR2A kinase domain	kd	0.0180	uM
3-amino-N-cyclohexyl-6-(4-methylphenyl)pyrazine-2-carboxamide	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.1800	uM
6-ethenyl-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.1900	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	436004: Binding constant for ACVR2A kinase domain	kd	0.2100	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.3100	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624838: Binding constant for ACVR2A kinase domain	kd	0.3200	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.5300	uM
6-cyclopropyl-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.6300	uM
6-ethyl-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.7000	uM
6-methoxy-3-[2-[(2-methylpropan-2-yl)oxy]-4-pyridinyl]-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.8000	uM
N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide	1992790: Inhibition of ACVR2A (unknown origin)	ic50	0.8600	uM
3-(2-cyclopropyloxy-4-pyridinyl)-6-methoxy-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.8600	uM
5-ethyl-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	0.9600	uM
3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	1.1000	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	1.2000	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-methylpyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	1.2000	uM
3-(2-methoxy-4-pyridinyl)-N,6-dimethylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	1.3000	uM
7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.12,6.017,20]docosa-1(20),2(22),3,5,14(21),15,18-heptaene	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	1.3000	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-(oxolan-3-yl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	1.9000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624838: Binding constant for ACVR2A kinase domain	kd	2.2000	uM
6-methoxy-5-(1-methylpyrazol-4-yl)-3-(2-propan-2-yloxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	2.3000	uM
1-[3-(2-cyclopropyloxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]oxy-2-methylpropan-2-ol	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	2.3000	uM
4-[6-[4-(1-pyrrolidin-1-ylethyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]naphthalene-1-sulfonamide	1417563: Inhibition of full length GST-tagged human ACVR2A expressed in Baculovirus expression system by LanthaScreen assay	ic50	2.3700	uM
3-(2-cyclobutyloxy-4-pyridinyl)-6-methoxy-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	2.4000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507821: Binding affinity to ACVR2A	kd	2.5000	uM
2-[6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidin-5-yl]propan-2-ol	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	2.7000	uM
5-[3-(2-cyclopropyloxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]oxy-2-methylpentan-2-ol	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	2.9000	uM
5-cyclopentyl-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	2.9000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	436004: Binding constant for ACVR2A kinase domain	kd	2.9000	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-N,N-dimethylpyrazolo[1,5-a]pyrimidin-5-amine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	3.0000	uM
4-[3-(2-cyclopropyloxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]oxy-2-methylbutan-2-ol	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	3.0000	uM
5-[6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidin-5-yl]-3-methyl-1,2-oxazole	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	3.0000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624838: Binding constant for ACVR2A kinase domain	kd	3.1000	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-propan-2-ylpyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	3.8000	uM
5-[(3S)-5,5-dimethyloxolan-3-yl]-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	4.1000	uM
5-[(3R)-5,5-dimethyloxolan-3-yl]-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709861: Inhibition of ACVR2A (unknown origin) using biotin- labelled KTLQDLVYDLSTSGSGSGLPLFVQRTVART substrate in presence of [gamma33P] ATP measured after 20 min	ic50	5.3000	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	624838: Binding constant for ACVR2A kinase domain	kd	8.9000	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1967379: Inhibition of ACVR2A (unknown origin) by LanthaScreen TR-FRET assay	ic50	9.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	3
Acetaminophen	increases expression, affects response to substance	3
bisphenol A	decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
potassium chromate(VI)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Urethane	increases expression	1
Vitamin E	decreases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Silver Compounds	increases expression	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

98 unique, capped per target: 98 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032240	Binding	Inhibition of ACVR2A at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem

Cellosaurus cell lines

2,179 cell lines: 2,178 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0248	DLD-1	Cancer cell line	Male
CVCL_0291	HCT 116	Cancer cell line	Male
CVCL_0397	LS180	Cancer cell line	Female
CVCL_0399	LoVo	Cancer cell line	Male
CVCL_0504	RKO	Cancer cell line	Sex unspecified
CVCL_1331	KM12	Cancer cell line	Male
CVCL_1724	SW48	Cancer cell line	Female
CVCL_1Q94	H414	Cancer cell line	Male
CVCL_1Q95	H414-LIG4(+/-)	Cancer cell line	Male
CVCL_1Q96	H414-MDC1(+/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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