ACVR1

Summary

ACVR1 (activin A receptor type 1, HGNC:171) is a protein-coding gene on chromosome 2q24.1, encoding Activin receptor type-1 (Q04771). Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. In precision oncology, ACVR1 G328V confers sensitivity to ALK2 Inhibitor LDN-193189 in Diffuse Midline Glioma, H3 K27-altered (CIViC Level D); 2 further curated variant–drug associations are listed below.

Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which signals a particular transcriptional response in concert with activin type II receptors. Mutations in this gene are associated with fibrodysplasia ossificans progressive.

Source: NCBI Gene 90 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fibrodysplasia ossificans progressiva (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 451 total — 16 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes — 39 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_001111067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:171
Approved symbol	ACVR1
Name	activin A receptor type 1
Location	2q24.1
Locus type	gene with protein product
Status	Approved
Aliases	SKR1, ALK2, ACVR1A
Ensembl gene	ENSG00000115170
Ensembl biotype	protein_coding
OMIM	102576
Entrez	90

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 45 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000263640, ENST00000409283, ENST00000410057, ENST00000412025, ENST00000413751, ENST00000424669, ENST00000434821, ENST00000440523, ENST00000487456, ENST00000539637, ENST00000672582, ENST00000673324, ENST00000681995, ENST00000682025, ENST00000682300, ENST00000682690, ENST00000683404, ENST00000683426, ENST00000683441, ENST00000683487, ENST00000683514, ENST00000683820, ENST00000684104, ENST00000684348, ENST00000684567, ENST00000684595, ENST00000864651, ENST00000864652, ENST00000864653, ENST00000864654, ENST00000864655, ENST00000864656, ENST00000864657, ENST00000864658, ENST00000864659, ENST00000864660, ENST00000864661, ENST00000864662, ENST00000864663, ENST00000864664, ENST00000933462, ENST00000945751, ENST00000945752, ENST00000945753, ENST00000945754, ENST00000945755, ENST00000945756, ENST00000945757, ENST00000945758, ENST00000945759, ENST00000945760, ENST00000945761

RefSeq mRNA: 7 — MANE Select: NM_001111067 NM_001105, NM_001111067, NM_001347663, NM_001347664, NM_001347665, NM_001347666, NM_001347667

CCDS: CCDS2206

Canonical transcript exons

ENST00000434821 — 11 exons

Exon	Start	End
ENSE00000924664	157799427	157799500
ENSE00000964338	157760880	157761077
ENSE00000964339	157738440	157738570
ENSE00001009616	157765921	157766196
ENSE00001009617	157770368	157770514
ENSE00001009618	157774088	157774187
ENSE00001174002	157778131	157778342
ENSE00001380537	157818385	157818559
ENSE00003536438	157780337	157780600
ENSE00003890265	157736446	157737665
ENSE00003893102	157875796	157876330

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0049 / max 141.5929, expressed in 1787 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31417	9.3512	1745
31418	7.1672	1698
31416	2.3395	1217
31419	0.8904	531
31414	0.1631	63
31415	0.0936	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	98.75	gold quality
synovial joint	UBERON:0002217	96.59	gold quality
saphenous vein	UBERON:0007318	95.61	gold quality
stromal cell of endometrium	CL:0002255	95.31	gold quality
urethra	UBERON:0000057	93.71	gold quality
islet of Langerhans	UBERON:0000006	93.14	gold quality
secondary oocyte	CL:0000655	93.08	gold quality
periodontal ligament	UBERON:0008266	93.04	gold quality
ventricular zone	UBERON:0003053	92.32	gold quality
layer of synovial tissue	UBERON:0007616	91.93	gold quality
choroid plexus epithelium	UBERON:0003911	91.83	gold quality
mammary duct	UBERON:0001765	91.81	gold quality
penis	UBERON:0000989	91.28	gold quality
epithelium of mammary gland	UBERON:0003244	90.99	gold quality
hair follicle	UBERON:0002073	90.91	gold quality
visceral pleura	UBERON:0002401	90.90	gold quality
corpus epididymis	UBERON:0004359	90.86	gold quality
gall bladder	UBERON:0002110	90.52	gold quality
pericardium	UBERON:0002407	90.44	gold quality
lower lobe of lung	UBERON:0008949	90.34	gold quality
blood vessel layer	UBERON:0004797	90.20	gold quality
descending thoracic aorta	UBERON:0002345	90.13	gold quality
thoracic mammary gland	UBERON:0005200	90.08	gold quality
pleura	UBERON:0000977	89.97	gold quality
mammary gland	UBERON:0001911	89.93	gold quality
parietal pleura	UBERON:0002400	89.86	gold quality
popliteal artery	UBERON:0002250	89.81	gold quality
tibial artery	UBERON:0007610	89.80	gold quality
bronchial epithelial cell	CL:0002328	89.56	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.37

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
HAMP	Activation
MSX1	Activation
SNAI1	Activation

Upstream regulators (CollecTRI, top): DLX3, DLX5, EGR1, EGR2, HEY1, SMAD1, ZBTB7A

miRNA regulators (miRDB)

130 targeting ACVR1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• distribution in gestational tissues across human pregnancy and during labour (PMID:11969340)
• We mapped fibrodysplasia ossificans progressiva to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G –> A; R206H) in the glycine-serine (GS) activation domain of ACVR1 (PMID:16642017)
• Study examined 3 Japanese patients with Fibrodysplasia ossificans progressiva for ACVR1 mutations and identified the 617G>A mutation in all 3 patients; results suggest that the mutation in the ACVR1 gene is common and recurrent in the global population. (PMID:17351709)
• knockdown of ALK2, but not TGFbetaRI (ALK5), abrogated endoglin-mediated decreases in cell motility and constitutively active ALK2 was sufficient to restore a low-motility phenotype in endoglin deficient cells (PMID:17496924)
• In both the wild-type ACVR1 model and template crystal structures (TbetaRI), the conserved arginine appears to form a salt bridge with an invariant aspartate residue. (PMID:17572636)
• Various mutations may occur in myositis ossificans nuclear families. (PMID:18019378)
• Together, these findings show that TGFbeta superfamily activation of Smad2/3 is required for repression of spontaneous differentiation under strain. (PMID:18234825)
• there was significant down-regulation of ALK-2 expression in asthma patients at baseline; allergy challenge was associated with upregulation (PMID:18292470)
• ALK2(R206H) with Smad1 or Smad5 induced osteoblastic differentiation that could be inhibited by Smad7 or dorsomorphin. (PMID:18684712)
• The novel amino-acid substitution is predicted to influence either the conformation/stability of the GS region or the binding affinity with FKBP12, resulting in a less stringent inhibitory control on the ACVR1 kinase activity. (PMID:18830232)
• ALK2 signalling contributes to the disturbed folliculogenesis in polycystic ovary syndrome (PCOS) patients. (PMID:18854405)
• ALK2(G356D) activities found in Japanese fibrodysplasia ossificans progressiva patient were weaker than those of ALK2(R206H), and they were suppressed by a specific inhibitor of the BMP-regulated Smad pathway. (PMID:18952055)
• The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size. (PMID:19028479)
• Study showed that all patients examined have heterozygous ACVR1 missense mutations in conserved amino acids. (PMID:19085907)
• activin inhibits the growth of SNU-16 cells by inducing apoptosis through caspase activation. (PMID:19148527)
• This study aimed to investigate the ACVR1 gene mutation in Chinese FOP patients. Direct sequence analysis of genomic DNA and restriction enzyme digestion demonstrated the presence of a single heterozygous mutation in the ACVR1 gene in both patients. (PMID:19300893)
• two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients; disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation (PMID:19330033)
• Data show that co-expressing constitutively active type I and type II receptors resulted in the phosphorylation of both R-Smad subclasses in a ligand-independent manner. (PMID:19335617)
• NOG & 617G>A activin A type I receptor(ACVRI)mutations in 27 fibrodysplasia ossificans patients; 5 NOG mutations found in 7 patients; 617G>A mutation in ACVR1 gene found in 14 patients; with 1 exception, 617G>A & NOG mutations were mutually exclusive (PMID:19400542)
• Dominant-negative ALK2 allele associates with congenital heart defects. (PMID:19506109)
• ACVR1 gene mutations were found heterozygous point mutation of c.617G>A; p.R206H in Myositis Ossificans. (PMID:19543505)
• Endoglin is phosphorylated on cytosolic domain threonine residues by the TGF-beta type I receptors ALK2 in prostate cancer cells. In the presence of constitutively active ALK2, endoglin did not inhibit cell migration (PMID:19736306)
• a variant of fibrodysplasia ossificans progressiva phenotypes are associated with specific mutations in ACVR1 gene (PMID:19796185)
• The discovery of the FOP metamorphogene reveals a highly conserved target for drug development and identifies a fundamental defect in the BMP signaling pathway that when triggered by injury and inflammation transforms one tissue into another. (PMID:19896889)
• The R206H mutation in ALK2 confers constitutive activity to the mutant receptor, sensitizes mesenchymal cells to BMP-induced osteoblast differentiation, and stimulates new bone formation. (PMID:19929436)
• BMP9 acts as a proliferative factor for immortalized ovarian surface epithelial cells and ovarian cancer cell lines, signaling predominantly through an ALK2/Smad1/Smad4 pathway, the major BMP9 receptor in endothelial cells. (PMID:19996292)
• Of 51 microsatellite stable colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression. (PMID:20011542)
• The impact of ACVR1 R206H mutation on BMP signaling and its downstream signaling cascades in murine myogenic C2C12 cells and HEK 293 cells, was studied. (PMID:20463014)
• Progressive heterotopic ossification along with congenital malformation of the great toes, the two major clinical features that define classic FOP, led to a suspicion of FOP and to the definitive screening of the ACVR1 gene (PMID:20577760)
• in two cases of fibrodysplasia ossificans progressiva, heterozygous missense mutation 617G>A (R206H) was found (PMID:20736820)
• These data indicate that in the context of a Down’s syndrome background, ALK2-mediated reduction of BMP signaling may contribute to congenital heart defects. (PMID:21248739)
• ACVR1 is associated with acute lung injury in mice (PMID:21297076)
• These findings suggest that ALK2(L196P) is an activated BMP receptor equivalent to ALK2(R206H) and that ALK2(L196P) activity may be suppressed in vivo by a novel molecular mechanism in fibrodysplasia ossificans progressiva patients with this mutation. (PMID:21377447)
• Low activin A in the cytosol is associated with upper urinary tract urothelial carcinoma. (PMID:21617230)
• copy number alterations at 2q24 can be involved in ACVR1 overexpression, which is associated with longer overall survival in laryngeal carcinomas (PMID:21668474)
• miR-30c expression was increased during adipogenesis of multipotent adipose-derived stem cells; miRNA target prediction revealed 2 putative direct targets of miR-30c, PAI-1 and ALK2, both inversely regulated to miR-30c during adipogenesis and responsive to miR-30c overexpression (PMID:21878751)
• miR-148a is an important mediator of ACVR1, thus offering a new potential target for the development of therapeutic agents against Fibrodysplasia ossificans progressiva. (PMID:22408438)
• Fibrodysplasia ossificans progressiva has been linked to an autosomal dominant mutation on chromosome 2, to the gene encoding activin receptor-like kinase 2 (ALK2), a BMP type I receptor (PMID:22630080)
• Confirmation of the presence of this recurrent mutation facilitates diagnostic accuracy in affected persons in South Africa, and allows researchers to narrow the search for molecular targets for rational intervention to the ACVR1/ALK2 domain. (PMID:22748444)
• Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo. (PMID:22884369)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Acvr1	ENSMUSG00000026836
rattus_norvegicus	Acvr1	ENSRNOG00000005033
drosophila_melanogaster	put	FBGN0003169
drosophila_melanogaster	tkv	FBGN0003716
drosophila_melanogaster	babo	FBGN0011300
caenorhabditis_elegans		WBGENE00000897
caenorhabditis_elegans		WBGENE00000900
caenorhabditis_elegans		WBGENE00004860

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Activin receptor type-1 — Q04771 (reviewed: Q04771)

Alternative names: Activin receptor type I, Activin receptor-like kinase 2, Serine/threonine-protein kinase receptor R1, TGF-B superfamily receptor type I

All UniProt accessions (9): A0A0S2Z2Y3, A0A0S2Z345, A0A1B0GXA9, A0A804HHZ2, A0A804HJQ0, C9JHJ7, C9JW28, D3DPA4, Q04771

UniProt curated annotations — full annotation on UniProt →

Function. Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B. Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain. In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs. May promote the expression of HAMP, potentially via its interaction with BMP6.

Subunit / interactions. Interacts with FKBP1A (PubMed:22484487, Ref.14). Interacts with FCHO1. Interacts with CLU. Interacts with type II receptors AMHR2 and ACVR2A. Interacts with BMP7. Interacts with GDF2/BMP9. Interacts with BMP6 (when glycosylated); the interaction may induce HAMP expression. Interacts with TSC22D1/TSC-22.

Subcellular location. Membrane.

Tissue specificity. Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells.

Disease relevance. Fibrodysplasia ossificans progressiva (FOP) [MIM:135100] A rare autosomal dominant connective tissue disorder resulting in skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to a debilitating ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (7): NP_001096, NP_001104537, NP_001334592, NP_001334593, NP_001334594, NP_001334595, NP_001334596 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003605	GS_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF01064, PF07714, PF08515

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 (64 total): strand 18, helix 15, sequence variant 13, mutagenesis site 3, turn 3, topological domain 2, domain 2, binding site 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6SRH	X-RAY DIFFRACTION	1.25
5S75	X-RAY DIFFRACTION	1.3
5S78	X-RAY DIFFRACTION	1.3
5S7A	X-RAY DIFFRACTION	1.3
5S7H	X-RAY DIFFRACTION	1.3
5S7I	X-RAY DIFFRACTION	1.3
5S7N	X-RAY DIFFRACTION	1.3
5S7S	X-RAY DIFFRACTION	1.3
5S7T	X-RAY DIFFRACTION	1.3
5S7X	X-RAY DIFFRACTION	1.3
5S7Z	X-RAY DIFFRACTION	1.3
5S87	X-RAY DIFFRACTION	1.3
5S89	X-RAY DIFFRACTION	1.3
5S8A	X-RAY DIFFRACTION	1.3
5S76	X-RAY DIFFRACTION	1.31
5S77	X-RAY DIFFRACTION	1.31
5S7C	X-RAY DIFFRACTION	1.31
5S7D	X-RAY DIFFRACTION	1.31
5S7F	X-RAY DIFFRACTION	1.31
5S7J	X-RAY DIFFRACTION	1.31
5S7K	X-RAY DIFFRACTION	1.31
5S7P	X-RAY DIFFRACTION	1.31
5S7V	X-RAY DIFFRACTION	1.31
5S86	X-RAY DIFFRACTION	1.31
5S88	X-RAY DIFFRACTION	1.31
5S7B	X-RAY DIFFRACTION	1.32
5S7E	X-RAY DIFFRACTION	1.32
5S7M	X-RAY DIFFRACTION	1.32
5S7W	X-RAY DIFFRACTION	1.33
5S83	X-RAY DIFFRACTION	1.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04771-F1	83.70	0.58

Antibody-complex structures (SAbDab): 1 — 7YRU

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): 336 (proton acceptor)

Ligand- & substrate-binding residues (2): 214–222; 235

Post-translational modifications (1): 501

Glycosylation sites (1): 102

Mutagenesis-validated functional residues (3):

Position	Phenotype
203	almost complete loss of alcaline phosphatase induction; in association with a-325.
207	strong induction of smad1 phosphorylation.
325	almost complete loss of alcaline phosphatase induction; in association with v-203.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 608 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER

GO Biological Process (53): branching involved in blood vessel morphogenesis (GO:0001569), osteoblast differentiation (GO:0001649), in utero embryonic development (GO:0001701), gastrulation with mouth forming second (GO:0001702), mesoderm formation (GO:0001707), neural crest cell migration (GO:0001755), acute inflammatory response (GO:0002526), embryonic heart tube morphogenesis (GO:0003143), atrioventricular valve morphogenesis (GO:0003181), mitral valve morphogenesis (GO:0003183), endocardial cushion formation (GO:0003272), endocardial cushion fusion (GO:0003274), atrial septum primum morphogenesis (GO:0003289), transforming growth factor beta receptor signaling pathway (GO:0007179), germ cell development (GO:0007281), determination of left/right symmetry (GO:0007368), heart development (GO:0007507), dorsal/ventral pattern formation (GO:0009953), negative regulation of signal transduction (GO:0009968), cell differentiation (GO:0030154), regulation of ossification (GO:0030278), positive regulation of cell migration (GO:0030335), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), activin receptor signaling pathway (GO:0032924), negative regulation of activin receptor signaling pathway (GO:0032926), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), smooth muscle cell differentiation (GO:0051145), pharyngeal system development (GO:0060037), positive regulation of SMAD protein signal transduction (GO:0060391), ventricular septum morphogenesis (GO:0060412), cardiac muscle cell fate commitment (GO:0060923), endocardial cushion cell fate commitment (GO:0061445), positive regulation of cardiac epithelial to mesenchymal transition (GO:0062043), cellular response to growth factor stimulus (GO:0071363), cellular response to BMP stimulus (GO:0071773), positive regulation of intracellular signal transduction (GO:1902533), positive regulation of determination of dorsal identity (GO:2000017)

GO Molecular Function (20): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), transforming growth factor beta receptor activity, type I (GO:0005025), ATP binding (GO:0005524), activin receptor activity, type I (GO:0016361), peptide hormone binding (GO:0017046), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), SMAD binding (GO:0046332), metal ion binding (GO:0046872), activin binding (GO:0048185), transforming growth factor beta binding (GO:0050431), BMP receptor activity (GO:0098821), protein tyrosine kinase binding (GO:1990782), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), growth factor binding (GO:0019838)

GO Cellular Component (5): plasma membrane (GO:0005886), apical part of cell (GO:0045177), activin receptor complex (GO:0048179), BMP receptor complex (GO:0070724), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endocardial cushion morphogenesis	2
protein binding	2
cellular anatomical structure	2
plasma membrane signaling receptor complex	2
angiogenesis	1
blood vessel morphogenesis	1
branching morphogenesis of an epithelial tube	1
ossification	1
cell differentiation	1
chordate embryonic development	1
gastrulation	1
formation of primary germ layer	1
mesoderm morphogenesis	1
neural crest cell development	1
mesenchymal cell migration	1
inflammatory response	1
heart morphogenesis	1
embryonic heart tube development	1
embryonic organ morphogenesis	1
embryonic morphogenesis	1
epithelial tube morphogenesis	1
atrioventricular valve development	1
heart valve morphogenesis	1
mitral valve development	1
atrioventricular valve morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell adhesion involved in heart morphogenesis	1
cell-cell adhesion	1
septum primum development	1
atrial septum morphogenesis	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
developmental process involved in reproduction	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
determination of bilateral symmetry	1
left/right pattern formation	1
animal organ development	1
circulatory system development	1

Protein interactions and networks

STRING

2178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACVR1	BMP6	P22004	995
ACVR1	BMP7	P18075	995
ACVR1	ACVR2A	P27037	988
ACVR1	BMPR2	Q13873	986
ACVR1	GDF2	Q9UK05	986
ACVR1	BMPR1A	P36894	978
ACVR1	BMP4	P12644	977
ACVR1	FKBP1A	P20071	977
ACVR1	CUL1	Q13616	963
ACVR1	BMPR1B	P78366	953
ACVR1	ACVR2B	Q13705	946
ACVR1	SMAD9	O15198	901
ACVR1	BMP2	P12643	877
ACVR1	TGFBR1	P36897	876
ACVR1	SMAD5	Q99717	876

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
TGFBRAP1	ACVR1	psi-mi:“MI:0914”(association)	0.730
ACVR1	BMPR1A	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
ACVR1	ADMP	psi-mi:“MI:0915”(physical association)	0.400
EPHA6	ACVR1	psi-mi:“MI:0915”(physical association)	0.400
Rhod	ACVR1	psi-mi:“MI:0915”(physical association)	0.400
Rab17	ACVR1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Ubxn1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Ikbkb	psi-mi:“MI:0915”(physical association)	0.400
Fbxo30	ACVR1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Rhebl1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Rab3b	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Nek8	psi-mi:“MI:0915”(physical association)	0.400
Fancl	ACVR1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Plekhb1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Chn1	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	Smad6	psi-mi:“MI:0915”(physical association)	0.400
ACVR1	TGFBR1	psi-mi:“MI:0915”(physical association)	0.370
	ABL1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
MRAP2	GOSR1	psi-mi:“MI:0914”(association)	0.350
LRRIQ1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (142): Rab17 (Affinity Capture-Luminescence), Rhoj (Affinity Capture-Luminescence), Rab33b (Affinity Capture-Luminescence), Rhod (Affinity Capture-Luminescence), Nras (Affinity Capture-Luminescence), Rab3b (Affinity Capture-Luminescence), Rras2 (Affinity Capture-Luminescence), Chn1 (Affinity Capture-Luminescence), Rps27a (Affinity Capture-Luminescence), Sqstm1 (Affinity Capture-Luminescence), Tgfbr1 (Affinity Capture-Luminescence), Plek (Affinity Capture-Luminescence), Plekhb1 (Affinity Capture-Luminescence), Ajuba (Affinity Capture-Luminescence), Fkbp4 (Affinity Capture-Luminescence)

ESM2 similar proteins: O00238, O08680, O42127, O42422, O46680, O73875, P09759, P22182, P29318, P29319, P29320, P29323, P36894, P36895, P36896, P36897, P36898, P37023, P37172, P54755, P54756, P54757, P54758, P54759, P54762, P70539, P80201, P80202, P80203, P80204, Q04771, Q05438, Q09488, Q15375, Q28041, Q5CD18, Q5RAN0, Q60629, Q61271, Q61288

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

16 interactions.

A	Effect	B	Mechanism
AMHR2	up-regulates	ACVR1	binding
4-[6-[4-(1-piperazinyl)phenyl]-3-pyrazolo[1,5-a]pyrimidinyl]quinoline	down-regulates	ACVR1	“chemical inhibition”
ACVR1	up-regulates	AMOT/MPP5/INADL/LIN7C	phosphorylation
ACVR1	“down-regulates activity”	AKT
ACVR1	“down-regulates activity”	AKT1
TGFBR1	“up-regulates activity”	ACVR1	phosphorylation
ACVR1	“form complex”	ACVR1/BMPR2	binding
BMPR2	up-regulates	ACVR1	binding
ACVR1	up-regulates	SMAD5	phosphorylation
ACVR1	up-regulates	SMAD1	phosphorylation
ACVR2A	up-regulates	ACVR1	binding
ACVR1	up-regulates	SMAD5
BMP7	up-regulates	ACVR1	binding
ACVR1	“up-regulates activity”	SMAD1	phosphorylation
ACVR1	“up-regulates activity”	VPS39	binding

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — HGGNOS, HNSC, UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	2
Uncertain significance	211
Likely benign	153
Benign	44

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1340352	GRCh37/hg19 2q23.3-24.1(chr2:154328530-158759642)x1	Pathogenic
1340408	GRCh37/hg19 2q23.3-24.1(chr2:154852961-159126250)x1	Pathogenic
146076	GRCh38/hg38 2q22.3-24.1(chr2:143900149-158321624)x3	Pathogenic
154597	GRCh38/hg38 2q23.3-24.2(chr2:151932344-159419734)x1	Pathogenic
18309	NM_001111067.4(ACVR1):c.617G>A (p.Arg206His)	Pathogenic
18310	NM_001111067.4(ACVR1):c.1067G>A (p.Gly356Asp)	Pathogenic
18311	NM_001111067.4(ACVR1):c.774G>C (p.Arg258Ser)	Pathogenic
208843	NM_001111067.4(ACVR1):c.587T>C (p.Leu196Pro)	Pathogenic
29593	NM_001111067.4(ACVR1):c.982G>A (p.Gly328Arg)	Pathogenic
29594	NM_001111067.4(ACVR1):c.982G>T (p.Gly328Trp)	Pathogenic
29596	NM_001111067.4(ACVR1):c.1124G>C (p.Arg375Pro)	Pathogenic
29597	NM_001111067.4(ACVR1):c.605G>T (p.Arg202Ile)	Pathogenic
3062503	GRCh37/hg19 2q24.1-24.3(chr2:157718631-165360287)x1	Pathogenic
443473	GRCh37/hg19 2q24.1-24.3(chr2:157970774-169270675)x1	Pathogenic
60216	GRCh38/hg38 2q22.3-24.1(chr2:147251948-157856378)x1	Pathogenic
60219	GRCh38/hg38 2q23.1-24.3(chr2:148917286-163204623)x1	Pathogenic
216885	NM_001111067.4(ACVR1):c.772A>G (p.Arg258Gly)	Likely pathogenic
236378	Single allele	Likely pathogenic

SpliceAI

3309 predictions. Top by Δscore:

Variant	Effect	Δscore
2:157737663:TGT:T	acceptor_gain	1.0000
2:157738434:TCTTA:T	donor_loss	1.0000
2:157738435:CTTAC:C	donor_loss	1.0000
2:157738436:TTAC:T	donor_loss	1.0000
2:157738437:TACCG:T	donor_loss	1.0000
2:157738438:A:AC	donor_gain	1.0000
2:157738438:A:C	donor_loss	1.0000
2:157738439:C:CC	donor_gain	1.0000
2:157738439:CCGGG:C	donor_gain	1.0000
2:157738499:T:A	donor_gain	1.0000
2:157738566:TATAC:T	acceptor_gain	1.0000
2:157738567:ATAC:A	acceptor_gain	1.0000
2:157738568:TAC:T	acceptor_gain	1.0000
2:157738569:AC:A	acceptor_gain	1.0000
2:157738570:CC:C	acceptor_gain	1.0000
2:157738571:C:CC	acceptor_gain	1.0000
2:157738574:C:CT	acceptor_gain	1.0000
2:157738576:C:CT	acceptor_gain	1.0000
2:157738578:C:CT	acceptor_gain	1.0000
2:157738579:A:T	acceptor_gain	1.0000
2:157761073:CAGGC:C	acceptor_gain	1.0000
2:157761074:AGGC:A	acceptor_gain	1.0000
2:157761075:GGC:G	acceptor_gain	1.0000
2:157761075:GGCC:G	acceptor_loss	1.0000
2:157761076:GC:G	acceptor_gain	1.0000
2:157761077:CC:C	acceptor_gain	1.0000
2:157761078:C:CC	acceptor_gain	1.0000
2:157761078:CTGA:C	acceptor_loss	1.0000
2:157761079:T:C	acceptor_loss	1.0000
2:157770511:TTCC:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000422 (2:157767164 TG>T), RS1000011250 (2:157790757 G>A), RS1000012035 (2:157764072 C>T), RS1000025538 (2:157856391 T>C), RS1000026135 (2:157810387 A>G), RS1000091219 (2:157876823 C>G,T), RS1000091871 (2:157817586 C>T), RS1000119592 (2:157741663 T>C), RS1000157099 (2:157739982 G>A,C), RS1000178084 (2:157829549 C>T), RS1000222218 (2:157787985 C>A), RS1000227946 (2:157793841 T>C), RS1000234461 (2:157791250 A>G), RS1000240138 (2:157773734 A>T), RS1000286088 (2:157771160 G>A,C)

Disease associations

OMIM: gene MIM:102576 | disease phenotypes: MIM:135100

GenCC curated gene-disease

Disease	Classification	Inheritance
fibrodysplasia ossificans progressiva	Definitive	Autosomal dominant
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
fibrodysplasia ossificans progressiva	Definitive	AD
congenital heart disease	Limited	AD

Mondo (5): fibrodysplasia ossificans progressiva (MONDO:0007606), congenital heart disease (MONDO:0005453), autism spectrum disorder (MONDO:0005258), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), 2q24 microdeletion syndrome (MONDO:0015566)

Orphanet (4): Fibrodysplasia ossificans progressiva (Orphanet:337), Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341), Developmental delay-language impairment-dopa responsive dystonia-parkinsonism syndrome due to 2q24 microdeletion (Orphanet:1617), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000687	Widely spaced teeth
HP:0000787	Nephrolithiasis
HP:0001004	Lymphedema
HP:0001172	Abnormal thumb morphology
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001376	Limitation of joint mobility
HP:0001385	Hip dysplasia
HP:0001482	Subcutaneous nodule
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001822	Hallux valgus
HP:0001844	Abnormal hallux morphology
HP:0001903	Anemia
HP:0002093	Respiratory insufficiency
HP:0002135	Basal ganglia calcification
HP:0002625	Deep venous thrombosis
HP:0002650	Scoliosis
HP:0002659	Increased susceptibility to fractures
HP:0002750	Delayed skeletal maturation
HP:0002878	Respiratory failure
HP:0002949	Fused cervical vertebrae
HP:0003016	Metaphyseal widening
HP:0003155	Elevated circulating alkaline phosphatase concentration

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004198_3	Severe gingival inflammation	5.000000e-06
GCST90020024_895	A body shape index	6.000000e-11
GCST90020025_1562	Waist-to-hip ratio adjusted for BMI	3.000000e-10
GCST90020027_465	Waist-hip index	1.000000e-10
GCST90020029_524	Waist circumference adjusted for body mass index	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C538316	Chromosome 2, monosomy 2q24 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5903 (SINGLE PROTEIN), CHEMBL6066857 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

39 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 148,701 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL124660	TANDUTINIB	2	2,530
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL253969	OSI-632	2	1,150
CHEMBL3544964	RAVOXERTINIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL5314579	ZILURGISERTIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL587723	AEE-788	2
CHEMBL5956963	KER-047	2
CHEMBL1090479	GSK-1070916	1

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items; also 10 diagnostic, 1 prognostic, 1 predisposing.

Variant	Therapy	Indication	Effect	Level	CIViC
ACVR1 G328V	ALK2 Inhibitor LDN-193189	Diffuse Midline Glioma, H3 K27-altered	Sensitivity/Response	CIViC D	EID6092
ACVR1 G328V	MEK-1/MEKK-1 Inhibitor E6201	Diffuse Midline Glioma, H3 K27-altered	Sensitivity/Response	CIViC D	EID8035
ACVR1 Mutation	ALK2 Inhibitor LDN-193189	Diffuse Midline Glioma, H3 K27-altered	Sensitivity/Response	CIViC D	EID10141

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
K02288	Inhibition	8.96	pIC50
compound 13d [PMID: 23639540]	Inhibition	8.3	pIC50
compound 13r [PMID: 23639540]	Inhibition	8.3	pIC50
momelotinib	Inhibition	8.08	pIC50
itacnosertib	Inhibition	8.0	pIC50
fidrisertib	Inhibition	8.0	pIC50
zilurgisertib	Inhibition	7.64	pIC50
LDN-214117	Inhibition	7.62	pIC50
ML347	Inhibition	7.49	pIC50
compound 13a [PMID: 23639540]	Inhibition	7.27	pIC50
BMS-986260	Inhibition	7.15	pIC50
compound 7 [Nguyen et al., 2023]	Inhibition	6.03	pIC50

Binding affinities (BindingDB)

94 measured of 126 human assays (126 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
4-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylquinoline	IC50	7.7 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	8 nM	US-9682983: BMP inhibitors and methods of use thereof
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
4-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	10 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	12 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[6-(2-piperazin-1-ylethoxy)-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	14 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-fluoro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	15 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(5-piperazin-1-yl-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	16 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[3-chloro-4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	16 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[6-[2-(4-methylpiperazin-1-yl)ethoxy]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	17 nM	US-9682983: BMP inhibitors and methods of use thereof
5-piperazin-1-yl-2-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)-1,3-thiazole	IC50	19 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[6-[(2S,6R)-2,6-dimethylpiperazin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	22 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[6-(2-piperazin-1-ylethoxy)-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	22 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	23 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(4-piperidin-4-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	23 nM	US-9682983: BMP inhibitors and methods of use thereof
2-chloro-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	24 nM	US-9682983: BMP inhibitors and methods of use thereof
2-piperazin-1-yl-5-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)benzonitrile	IC50	24 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-8-carboxamide	IC50	26 nM	US-9682983: BMP inhibitors and methods of use thereof
BMS-354825	KD	27 nM
5-[6-[5-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	28 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	29 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-chloro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	30 nM	US-9682983: BMP inhibitors and methods of use thereof
US10017516, Compound 28	IC50	31 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(3-fluoro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	32 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylquinoline	IC50	32 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-[(3S)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	34 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	38 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(5-piperidin-4-yloxy-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	41 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	43 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-(1-methylpiperidin-4-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	43 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-amine	IC50	44 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-[(3R)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	45 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(3-chloro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	46 nM	US-9682983: BMP inhibitors and methods of use thereof
2-piperazin-1-yl-5-(3-quinolin-5-ylpyrazolo[1,5-a]pyrimidin-6-yl)benzonitrile	IC50	47 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[6-[(2R,6S)-2,6-dimethylpiperazin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	56 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[3-chloro-4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	56 nM	US-9682983: BMP inhibitors and methods of use thereof
[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-8-yl]methanol	IC50	62 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-2-one	IC50	66 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-piperazin-1-ylprop-1-ynyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	68 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	84 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	85 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-8-carboxylic acid	IC50	88 nM	US-9682983: BMP inhibitors and methods of use thereof
[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]methanol	IC50	102 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-[(3S)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	102 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(2-piperazin-1-ylpyrimidin-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	103 nM	US-9682983: BMP inhibitors and methods of use thereof
N-[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]acetamide	IC50	105 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxyphenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	106 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	107 nM	US-9682983: BMP inhibitors and methods of use thereof
4-(6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin- 3-yl)quinoline	IC50	108 nM

ChEMBL bioactivities

1810 potent at pChembl≥5 of 1860 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.07	IC50	0.85	nM	CHEMBL5184000
9.01	IC50	0.98	nM	CHEMBL5181536
9.00	IC50	1	nM	CHEMBL4790396
8.96	IC50	1.1	nM	CHEMBL1230714
8.92	IC50	1.2	nM	CHEMBL3818173
8.92	IC50	1.2	nM	CHEMBL5199417
8.89	IC50	1.3	nM	CHEMBL5186341
8.89	IC50	1.3	nM	CHEMBL5181872
8.89	IC50	1.3	nM	CHEMBL5961222
8.82	Kd	1.506	nM	CHEMBL3752910
8.80	Ki	1.585	nM	PD-0166285
8.70	IC50	2	nM	CHEMBL5630864
8.70	IC50	2	nM	CHEMBL5630109
8.70	IC50	2	nM	CHEMBL5631116
8.70	IC50	2	nM	CHEMBL6055910
8.60	IC50	2.5	nM	CHEMBL5171699
8.57	IC50	2.7	nM	CHEMBL6007636
8.54	IC50	2.9	nM	CHEMBL5200241
8.52	IC50	3	nM	CHEMBL4575655
8.52	IC50	3	nM	CHEMBL4526828
8.52	IC50	3	nM	CHEMBL4548795
8.52	IC50	3	nM	CHEMBL4638273
8.52	IC50	3	nM	CHEMBL5630025
8.52	IC50	3	nM	CHEMBL5630485
8.52	IC50	3	nM	CHEMBL6047714
8.52	IC50	3	nM	CHEMBL5937211
8.52	IC50	3	nM	CHEMBL6022086
8.52	IC50	3	nM	CHEMBL6055852
8.52	IC50	3	nM	CHEMBL6013418
8.52	IC50	3	nM	CHEMBL5769020
8.52	IC50	3	nM	CHEMBL5851290
8.52	IC50	3	nM	CHEMBL6050510
8.52	IC50	3	nM	CHEMBL5908313
8.52	IC50	3	nM	CHEMBL5871168
8.52	IC50	3	nM	CHEMBL5821076
8.52	IC50	3	nM	CHEMBL6003450
8.52	IC50	3	nM	CHEMBL5859003
8.52	IC50	3	nM	CHEMBL5828024
8.52	IC50	3	nM	CHEMBL5855334
8.52	IC50	3	nM	CHEMBL5861691
8.52	IC50	3	nM	CHEMBL5801457
8.52	IC50	3	nM	CHEMBL5939714
8.52	IC50	3	nM	CHEMBL6030902
8.52	IC50	3	nM	CHEMBL5781701
8.52	IC50	3	nM	CHEMBL5926517
8.52	IC50	3	nM	CHEMBL5936945
8.52	IC50	3	nM	CHEMBL5794905
8.52	IC50	3	nM	CHEMBL5896243
8.52	IC50	3	nM	CHEMBL5780773
8.52	IC50	3	nM	CHEMBL6061439

PubChem BioAssay actives

534 with measured affinity, of 1189 total; 50 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
methyl (3R,5S)-3,5-dimethyl-4-[3-[6-[(3R)-3-methylpiperazin-1-yl]-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazine-1-carboxylate	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0008	uM
methyl (3S,5R)-3,5-dimethyl-4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazine-1-carboxylate	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0010	uM
7-[7-[4-(4-methylpiperazin-1-yl)phenyl]imidazo[1,2-a]pyridin-3-yl]thieno[2,3-b]pyrazine	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0010	uM
3-[6-amino-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenol	1877423: Inhibition of GST-tagged human recombinant ALK2 (145 to 509 residues) expressed in baculovirus expression system using casein as substrate in presence of [gamma-32P]ATP incubated for 45 mins by Microscint-20 scintillation counting analysis	ic50	0.0011	uM
[(3S,5R)-3,5-dimethyl-4-[3-[6-[(3R)-3-methylpiperazin-1-yl]-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazin-1-yl]-pyrrolidin-1-ylmethanone	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0012	uM
methyl (3S,5R)-4-[3-[3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3,5-dimethylpiperazine-1-carboxylate	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0013	uM
methyl (3S,5R)-3,5-dimethyl-4-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazine-1-carboxylate	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0013	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147800: Binding affinity to human ACVR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0015	uM
2-chloro-6-methoxy-4-[4-methyl-5-(4-piperazin-1-ylphenyl)-3-pyridinyl]benzamide	1607596: Inhibition of ALK2 G328V mutant (unknown origin)	ic50	0.0020	uM
2,6-dimethoxy-4-[4-methyl-5-[4-(4-methylpiperazin-1-yl)phenyl]-3-pyridinyl]benzamide	1607596: Inhibition of ALK2 G328V mutant (unknown origin)	ic50	0.0020	uM
9-piperazin-1-yl-4-(3,4,5-trimethoxyphenyl)-5,6-dihydro-[1]benzoxepino[5,4-c]pyridine	2135210: Inhibition of N-terminal GST-his6 tagged human recombinant ALK2 (145 to 509 residues) expressed in Sf9 insect cells in presence of ATP by ADP-glo assay	ic50	0.0020	uM
9-(4-methylpiperazin-1-yl)-4-(3,4,5-trimethoxyphenyl)-5,6-dihydro-[1]benzoxepino[5,4-c]pyridine	2135210: Inhibition of N-terminal GST-his6 tagged human recombinant ALK2 (145 to 509 residues) expressed in Sf9 insect cells in presence of ATP by ADP-glo assay	ic50	0.0020	uM
9-piperazin-1-yl-4-(3,4,5-trimethoxyphenyl)-5,7-dihydro-[2]benzoxepino[5,4-c]pyridine	2135210: Inhibition of N-terminal GST-his6 tagged human recombinant ALK2 (145 to 509 residues) expressed in Sf9 insect cells in presence of ATP by ADP-glo assay	ic50	0.0020	uM
5-[(2S,6R)-2,6-dimethylpiperidin-1-yl]-3-[6-[(3R)-3-methylpiperazin-1-yl]-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidine	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0025	uM
8-amino-2-cyclohexyl-5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-3,4-dihydro-2,7-naphthyridin-1-one	1877428: Inhibition of ALK2 (unknown origin)	ic50	0.0029	uM
2,6-dimethoxy-4-[4-methyl-5-[4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl]-3-pyridinyl]benzamide	1607562: Inhibition of human ALK2 using casein as substrate in presence of 10 uM [gamma33P] ATP by radioactive assay	ic50	0.0030	uM
2-fluoro-6-methoxy-4-[4-methyl-5-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]-3-pyridinyl]benzamide	1607596: Inhibition of ALK2 G328V mutant (unknown origin)	ic50	0.0030	uM
2-fluoro-6-methoxy-4-[4-methyl-5-[4-(4-methylpiperazin-1-yl)phenyl]-3-pyridinyl]benzamide	1607562: Inhibition of human ALK2 using casein as substrate in presence of 10 uM [gamma33P] ATP by radioactive assay	ic50	0.0030	uM
3-(4-piperazin-1-ylphenyl)-5-(3,4,5-trimethoxyphenyl)pyridine-4-carbonitrile	1665308: Inhibition of human ALK2 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.0030	uM
6-methyl-9-piperazin-1-yl-4-(3,4,5-trimethoxyphenyl)-5,7-dihydropyrido[4,3-d][2]benzazepine	2135210: Inhibition of N-terminal GST-his6 tagged human recombinant ALK2 (145 to 509 residues) expressed in Sf9 insect cells in presence of ATP by ADP-glo assay	ic50	0.0030	uM
9-(4-methylpiperazin-1-yl)-4-(3,4,5-trimethoxyphenyl)-5,7-dihydro-[2]benzoxepino[5,4-c]pyridine	2135210: Inhibition of N-terminal GST-his6 tagged human recombinant ALK2 (145 to 509 residues) expressed in Sf9 insect cells in presence of ATP by ADP-glo assay	ic50	0.0030	uM
8-amino-2-cyclohexyl-5-(1-piperidin-4-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877428: Inhibition of ALK2 (unknown origin)	ic50	0.0032	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1431777: Inhibition of human ALK2 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	ic50	0.0033	uM
8-amino-2-cyclohexyl-5-(1-piperidin-3-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877428: Inhibition of ALK2 (unknown origin)	ic50	0.0035	uM
2-amino-5-[3-fluoro-4-[[(2R)-2-methylpyrrolidin-1-yl]methyl]phenyl]-N-(4-hydroxy-4-methylcyclohexyl)pyridine-3-carboxamide	1877426: Inhibition of human recombinant ALK2 (172 to 499 residues) expressed in baculovirus-infected insect cells by ADP-Glo kinase assay	ic50	0.0036	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-(3-methoxy-4-pyridinyl)pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112252: Inhibition of ALK2 (unknown origin) by TR-FRET assay	ic50	0.0039	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424900: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0040	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624819: Binding constant for ACVR1 kinase domain	kd	0.0040	uM
2-fluoro-6-methoxy-4-[4-methyl-5-(4-piperazin-1-ylphenyl)-3-pyridinyl]benzamide	1607596: Inhibition of ALK2 G328V mutant (unknown origin)	ic50	0.0040	uM
N,N-dimethyl-4-[4-[4-methyl-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]piperazine-1-carboxamide	1665308: Inhibition of human ALK2 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.0040	uM
2-[4-[2-(diethylamino)ethoxy]anilino]-8-ethyl-6-phenylpyrido[2,3-d]pyrimidin-7-one	1756905: Inhibition of human ALK2 using casein as substrate incubated for 30 mins in presence of [gamma33P]ATP by radiometric hotspot kinase assay	ic50	0.0040	uM
8-amino-2-cyclohexyl-5-[1-(piperidin-4-ylmethyl)pyrazol-4-yl]-3,4-dihydro-2,7-naphthyridin-1-one	1877428: Inhibition of ALK2 (unknown origin)	ic50	0.0044	uM
ethyl (3S,5R)-3,5-dimethyl-4-[3-[6-[(3R)-3-methylpiperazin-1-yl]-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazine-1-carboxylate	1870519: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay	ic50	0.0049	uM
N-[3-[2-amino-5-(4-piperazin-1-ylphenyl)-3-pyridinyl]-5-methoxyphenyl]methanesulfonamide	1739684: Inhibition of human ALK2 using casein as substrate in presence of 10 uM [gamma33P] ATP by kinase assay	ic50	0.0050	uM
N-[3-[2-amino-5-(4-piperazin-1-ylphenyl)-3-pyridinyl]-5-methoxyphenyl]benzenesulfonamide	1739684: Inhibition of human ALK2 using casein as substrate in presence of 10 uM [gamma33P] ATP by kinase assay	ic50	0.0050	uM
6-fluoro-2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
3-[4-[3-(2-methylquinolin-4-yl)imidazo[1,2-a]pyridin-7-yl]phenyl]morpholine	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
3-[4-[3-(6-fluoro-2-methylquinolin-4-yl)imidazo[1,2-a]pyridin-7-yl]phenyl]morpholine	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
2-methoxy-4-[4-methyl-5-(4-piperazin-1-ylphenyl)-3-pyridinyl]benzamide	1607596: Inhibition of ALK2 G328V mutant (unknown origin)	ic50	0.0050	uM
4-methyl-3-[4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]-5-(3,4,5-trimethoxyphenyl)pyridine	1665308: Inhibition of human ALK2 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.0050	uM
2,6-dimethoxy-4-[4-methyl-5-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]-3-pyridinyl]benzamide	1607562: Inhibition of human ALK2 using casein as substrate in presence of 10 uM [gamma33P] ATP by radioactive assay	ic50	0.0050	uM
2,6-dimethoxy-4-[4-methyl-5-(4-piperazin-1-ylphenyl)-3-pyridinyl]benzamide	1607562: Inhibition of human ALK2 using casein as substrate in presence of 10 uM [gamma33P] ATP by radioactive assay	ic50	0.0050	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424900: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0050	uM
4-[6-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750130: Inhibition of ALK2 (unknown origin)	ic50	0.0050	uM
4-[4-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]morpholine	750130: Inhibition of ALK2 (unknown origin)	ic50	0.0050	uM
2-(2-adamantyl)-8-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877428: Inhibition of ALK2 (unknown origin)	ic50	0.0053	uM
3-[4-[3-(6,8-difluoro-2-methylquinolin-4-yl)imidazo[1,2-a]pyridin-7-yl]phenyl]morpholine	1722077: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0056	uM
N-[3-[6-amino-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]methanesulfonamide	1186982: Inhibition of human recombinant human ALK2 kinase after 45 mins by liquid scintillation counting in presence of ATP [gamma-32P]	ic50	0.0060	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, increases methylation	3
sodium arsenite	increases expression, increases methylation	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cyclosporine	increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	2
Carbamazepine	affects expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
pinostrobin	increases expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Leflunomide	increases expression	1
Glyphosate	increases expression	1
Ethanol	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Coumestrol	decreases expression	1
Diclofenac	affects expression	1
Lead	affects expression	1

ChEMBL screening assays

299 unique, capped per target: 293 binding, 4 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032238	Binding	Inhibition of ACVR1 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
CHEMBL1963721	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ACVR1	PubChem BioAssay data set
CHEMBL3998847	ADMET	Inhibition of human ALK2 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	Identification of the First Selective Activin Receptor-Like Kinase 1 Inhibitor, a Reversible Version of L-783277. — J Med Chem

Cellosaurus cell lines

30 cell lines: 18 induced pluripotent stem cell, 11 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9S03	BCRTi001-A	Induced pluripotent stem cell	Male
CVCL_9S04	BCRTi002-A	Induced pluripotent stem cell	Female
CVCL_A0LJ	TRNDi012-A	Induced pluripotent stem cell	Female
CVCL_A0LK	TRNDi012-B	Induced pluripotent stem cell	Female
CVCL_A0LL	TRNDi012-C	Induced pluripotent stem cell	Female
CVCL_A0LM	TRNDi012-D	Induced pluripotent stem cell	Female
CVCL_A0LN	TRNDi012-E	Induced pluripotent stem cell	Female
CVCL_A0LP	TRNDi012-F	Induced pluripotent stem cell	Female
CVCL_A0LQ	TRNDi012-G	Induced pluripotent stem cell	Female
CVCL_A0LR	TRNDi012-H	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT03312634	PHASE3	COMPLETED	An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.
NCT05027802	PHASE3	COMPLETED	A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.
NCT05394116	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)
NCT07559513	PHASE3	NOT_YET_RECRUITING	A Study to Investigate the Safety, Pharmacokinetics (PK), and Efficacy of Garetosmab in Children and Adolescents With Fibrodysplasia Ossificans Progressiva (FOP)
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT02190747	PHASE2	COMPLETED	An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects
NCT02279095	PHASE2	COMPLETED	An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
NCT02521792	PHASE2	TERMINATED	In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects
NCT03188666	PHASE2	COMPLETED	A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva
NCT04307953	PHASE2	UNKNOWN	Saracatinib Trial TO Prevent FOP
NCT05039515	PHASE2	TERMINATED	A Study to Assess the Effectiveness and Safety of 2 Dosage Regimens of Oral Fidrisertib (IPN60130) for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP).
NCT05090891	PHASE2	RECRUITING	To Assess the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery