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): 459 total — 13 pathogenic, 2 likely-pathogenic (top 7% of genes corpus-wide)
• GTEx eGene: eQTL in 6 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 54
• Drug target: yes — 4 curated mechanism-of-action drugs; 39 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 4 — Dibotermin Alfa, Eptotermin Alfa, Momelotinib Dihydrochloride Monohydrate, +1 more
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• 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: 54 — 45 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 3 nonsense_mediated_decay

MANE Select: ENST00000434821

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 3: 2, TSL 4: 4, TSL 5: 1

ENST00000434821, ENST00000263640, ENST00000409283, ENST00000410057, ENST00000412025, ENST00000413751, ENST00000424669, ENST00000440523, ENST00000487456, ENST00000539637, ENST00000672582, 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, ENST00001042656, ENST00001042657, ENST00001145287

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.

Highest expression (Bgee): cartilage tissue, synovial joint, saphenous vein, stromal cell of endometrium, urethra.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACVR1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

9 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	1.3e-04	-0.41	2:157819056:T:C
Thyroid	sqtl	3.5e-04	+0.96	2:158713666:T:A
Whole Blood	eqtl	6.1e-03	+0.12	2:158152357:G:A
Skin Sun Exposed Lower leg	eqtl	7.5e-03	+0.24	2:158660155:G:A
Esophagus Muscularis	eqtl	1.3e-02	+0.27	2:157866444:C:CGG
Adipose Subcutaneous	eqtl	1.3e-02	+0.46	2:157556951:C:A
Esophagus Muscularis	sqtl	2.6e-02	+1.51	2:157783920:C:A
Muscle Skeletal	eqtl	4.2e-02	+0.29	2:158753562:T:C
Brain Cerebellar Hemisphere	eqtl	4.6e-02	+0.27	2:158769371:C:T

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

showing 100 of 299 tissues 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
aorta	UBERON:0000947	89.42	gold quality
artery	UBERON:0001637	89.35	gold quality
ganglionic eminence	UBERON:0004023	89.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.20	gold quality
myometrium	UBERON:0001296	89.06	gold quality
smooth muscle tissue	UBERON:0001135	88.89	gold quality
thoracic aorta	UBERON:0001515	88.86	gold quality
caput epididymis	UBERON:0004358	88.82	gold quality
tibia	UBERON:0000979	88.77	gold quality
skin of hip	UBERON:0001554	88.76	gold quality
ascending aorta	UBERON:0001496	88.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.69	gold quality
endocervix	UBERON:0000458	88.51	gold quality
cortical plate	UBERON:0005343	88.51	gold quality
right coronary artery	UBERON:0001625	88.15	gold quality
germinal epithelium of ovary	UBERON:0001304	87.76	gold quality
vena cava	UBERON:0004087	87.58	silver quality
cauda epididymis	UBERON:0004360	87.54	gold quality
body of uterus	UBERON:0009853	87.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.47	gold quality
upper leg skin	UBERON:0004262	87.45	gold quality
epithelium of nasopharynx	UBERON:0001951	87.42	gold quality
left lobe of thyroid gland	UBERON:0001120	87.34	gold quality
thyroid gland	UBERON:0002046	87.34	gold quality
right lobe of thyroid gland	UBERON:0001119	87.22	gold quality
biceps brachii	UBERON:0001507	86.90	gold quality
gingival epithelium	UBERON:0001949	86.89	gold quality
left uterine tube	UBERON:0001303	86.85	gold quality
adipose tissue	UBERON:0001013	86.79	gold quality
superficial temporal artery	UBERON:0001614	86.76	gold quality
cardiac atrium	UBERON:0002081	86.75	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.73	gold quality
right atrium auricular region	UBERON:0006631	86.68	gold quality
connective tissue	UBERON:0002384	86.61	gold quality
ectocervix	UBERON:0012249	86.56	gold quality
uterus	UBERON:0000995	86.55	gold quality
left coronary artery	UBERON:0001626	86.46	gold quality
right ovary	UBERON:0002118	86.37	gold quality
coronary artery	UBERON:0001621	86.26	gold quality
trachea	UBERON:0003126	86.26	gold quality
urinary bladder	UBERON:0001255	86.24	gold quality
epithelial cell of pancreas	CL:0000083	86.21	gold quality
heart right ventricle	UBERON:0002080	86.20	gold quality
bronchus	UBERON:0002185	86.20	gold quality
decidua	UBERON:0002450	86.18	gold quality
gingiva	UBERON:0001828	86.17	gold quality
epithelium of bronchus	UBERON:0002031	86.17	gold quality
calcaneal tendon	UBERON:0003701	86.15	gold quality
palpebral conjunctiva	UBERON:0001812	86.05	gold quality
placenta	UBERON:0001987	85.99	gold quality
eye	UBERON:0000970	85.93	gold quality
adult organism	UBERON:0007023	85.80	gold quality
monocyte	CL:0000576	85.72	gold quality
mononuclear cell	CL:0000842	85.66	gold quality
oocyte	CL:0000023	85.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.59	gold quality
lower esophagus	UBERON:0013473	85.56	gold quality
pigmented layer of retina	UBERON:0001782	85.54	gold quality
retina	UBERON:0000966	85.52	gold quality
colonic epithelium	UBERON:0000397	85.51	gold quality
minor salivary gland	UBERON:0001830	85.49	gold quality
endometrium	UBERON:0001295	85.46	gold quality
peritoneum	UBERON:0002358	85.40	gold quality
omental fat pad	UBERON:0010414	85.39	gold quality
leukocyte	CL:0000738	85.36	gold quality
muscle tissue	UBERON:0002385	85.33	gold quality
mouth mucosa	UBERON:0003729	85.29	gold quality
female reproductive system	UBERON:0000474	85.23	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	44.9	low
Hippocampus	tissue	41.2	low
Olfactory bulb	tissue	37.0
Hippocampal formation	tissue	33.1
Choroid plexus	tissue	29.5
Thyroid gland	tissue	28.6	high
Smooth muscle	tissue	26.8	high
Superior colliculi	tissue	25.9
Caudate putamen	tissue	25.7
Cerebral cortex	tissue	24.9	low
Somatosensory cortex	tissue	24.9
Motor cortex	tissue	24.4
Occipital cortex	tissue	24.2
Spinal cord	tissue	24.0
Putamen	tissue	23.5
Thalamus	tissue	22.9
Retrosplenial and cingulate cortex	tissue	21.9
Entorhinal cortex	tissue	21.3
Retrosplenial cortex	tissue	21.2
Midbrain	tissue	21.1
Cervix	tissue	20.6	not detected
Pons	tissue	20.6
Substantia nigra	tissue	20.5
Prefrontal cortex	tissue	19.8
Basal ganglia	tissue	19.6	low
Temporal cortex	tissue	19.3
Insular cortex	tissue	19.2
Medulla oblongata	tissue	19.1
Nucleus accumbens	tissue	18.6
Septum	tissue	18.5
Ovary	tissue	17.7	low
Periaqueductal gray	tissue	17.4
Frontal cortex	tissue	17.2
Hypothalamus	tissue	17.1
Amygdala	tissue	16.7
Locus coeruleus	tissue	16.6
Corpus callosum	tissue	16.6
Endometrium 1	tissue	15.9	low
Postcentral gyrus	tissue	15.8
Ventral forebrain	tissue	15.8
Skeletal muscle	tissue	15.5	medium
Liver	tissue	15.3	low
Kidney	tissue	15.0	medium
Heart muscle	tissue	14.3	medium
Gallbladder	tissue	14.1	not detected
Urinary bladder	tissue	13.3	low
Fallopian tube	tissue	13.2	medium
Adipose tissue	tissue	12.6	low
Placenta	tissue	12.5	medium
Lung	tissue	12.2	low
Seminal vesicle	tissue	11.3
Breast	tissue	11.1	medium
Stomach 1	tissue	11.0	low
Epididymis	tissue	10.8	medium
Prostate	tissue	9.9	low
Appendix	tissue	9.2	low
Colon	tissue	8.5	low
Esophagus	tissue	8.2	low
Rectum	tissue	8.2	low
Small intestine	tissue	8.0	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Hippocampus, CA1 (46.0), Hippocampus, CA3 (40.5), Dentate gyrus (38.8), Dorsal hippocampus (33.1), Ventral hippocampus (30.6).

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)

Targeting ACVR1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 130 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.41e-08, LOEUF 0.835, missense Z 2.95 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000434821 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:157,737,534–157,761,051	146 / 186.6	0.78	no
2:157,761,052–157,774,167	114 / 216.2	0.53	no
2:157,774,168–157,799,493	203 / 235.5	0.86	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87911) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 108 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased embryo size	3
lethality throughout fetal growth and development, incomplete penetrance	3
abnormal embryo development	2
abnormal mesoderm development	2
abnormal gastrulation	2
embryonic growth arrest	2
abnormal motor capabilities/coordination/movement	2
abnormal primitive streak formation	2
absent allantois	2
abnormal embryonic epiblast morphology	2
ventricular septal defect	2
neonatal lethality, complete penetrance	2
increased bone ossification	2
abnormal malleus morphology	1
large anterior fontanelle	1
short mandible	1
abnormal cartilage morphology	1
abnormal heart morphology	1
enlarged heart	1
abnormal atrioventricular cushion morphology	1
decreased atrioventricular cushion size	1
shortened head	1
abnormal mandible morphology	1
mandible hypoplasia	1
muscle spasm	1

+83 more (showing top 25).

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Sus scrofa	Q66T47	99.2%	Diamond
Bos taurus	Q28041	99.0%	Diamond
Pongo abelii	Q5RAN0	99.0%	Diamond
Ovis aries	Q28560	98.6%	Diamond
Gallus gallus	Q90669	93.2%	Diamond
Xenopus laevis	P27039	91.4%	Diamond
Oryctolagus cuniculus	Q28616	79.5%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
UPP2	protein-coding	151531
ACVR1C	protein-coding	130399
CYTIP	protein-coding	9595

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)

• 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 (70 total): helix 21, strand 18, 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)

showing 30 of 85 structures by resolution:

PDB	Title	Method	Resolution (Å)
6SRH	Crystal structure of the ACVR1 (ALK2) kinase in complex with the compound M4K2117	X-RAY DIFFRACTION	1.25
5S75	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010913a	X-RAY DIFFRACTION	1.3
5S78	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010934a	X-RAY DIFFRACTION	1.3
5S7A	XChem group deposition – Crystal Structure of human ACVR1 in complex with PK012456b	X-RAY DIFFRACTION	1.3
5S7H	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010914a	X-RAY DIFFRACTION	1.3
5S7I	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010928a	X-RAY DIFFRACTION	1.3
5S7N	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010920a	X-RAY DIFFRACTION	1.3
5S7S	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010921a	X-RAY DIFFRACTION	1.3
5S7T	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010926a	X-RAY DIFFRACTION	1.3
5S7X	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM000376d	X-RAY DIFFRACTION	1.3
5S7Z	XChem group deposition – Crystal Structure of human ACVR1 in complex with NU074488b	X-RAY DIFFRACTION	1.3
5S87	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010953a	X-RAY DIFFRACTION	1.3
5S89	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010957a	X-RAY DIFFRACTION	1.3
5S8A	XChem group deposition – Crystal Structure of human ACVR1 in complex with NU074484b	X-RAY DIFFRACTION	1.3
5S76	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010916a	X-RAY DIFFRACTION	1.31
5S77	XChem group deposition – Crystal Structure of human ACVR1 in complex with XS035133b	X-RAY DIFFRACTION	1.31
5S7C	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM000274c	X-RAY DIFFRACTION	1.31
5S7D	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010923a	X-RAY DIFFRACTION	1.31
5S7F	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010935a	X-RAY DIFFRACTION	1.31
5S7J	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM000893d	X-RAY DIFFRACTION	1.31
5S7K	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010936a	X-RAY DIFFRACTION	1.31
5S7P	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010937a	X-RAY DIFFRACTION	1.31
5S7V	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010942a	X-RAY DIFFRACTION	1.31
5S86	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010952a	X-RAY DIFFRACTION	1.31
5S88	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010954a	X-RAY DIFFRACTION	1.31
5S7B	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM000329d	X-RAY DIFFRACTION	1.32
5S7E	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010930a	X-RAY DIFFRACTION	1.32
5S7M	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM000275d	X-RAY DIFFRACTION	1.32
5S7W	XChem group deposition – Crystal Structure of human ACVR1 in complex with HM000007h	X-RAY DIFFRACTION	1.33
5S83	XChem group deposition – Crystal Structure of human ACVR1 in complex with FM010948a	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 antibodies co-crystallized with this protein: 7YRU

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, TKL Ser/Thr protein kinases, Predicted membrane proteins, Predicted intracellular proteins, Cancer-related genes, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
336	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
214–222	ATP
235	ATP

Post-translational modifications (1)

Type	Positions
Phosphoserine	501

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	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 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (42): osteoblast differentiation (GO:0001649), 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), 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), 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), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), protein phosphorylation (GO:0006468), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), endothelial cell differentiation (GO:0045446), positive regulation of cell differentiation (GO:0045597), regulation of multicellular organismal process (GO:0051239), positive regulation of multicellular organismal process (GO:0051240), epithelial tube morphogenesis (GO:0060562), circulatory system development (GO:0072359), regulation of multicellular organismal development (GO:2000026)

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

showing 60 of 78 GO namespaces:

Category	Terms
transforming growth factor beta receptor superfamily signaling pathway	3
ossification	2
endocardial cushion morphogenesis	2
protein binding	2
cellular anatomical structure	2
plasma membrane signaling receptor complex	2
cell differentiation	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
animal organ development	1
circulatory system development	1
regionalization	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
cellular developmental process	1
regulation of multicellular organismal process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	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
activin receptor signaling pathway	1
regulation of activin receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein kinase activity	1
protein serine/threonine kinase activity	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
transmembrane receptor protein kinase activity	1
transforming growth factor beta receptor activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
activin receptor activity	1
hormone binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 37 of 67 annotations. The rest are phylogenetic / computational / electronic (IEA).

37 experimentally-supported GO terms:

GO term	NS	Evidence
BMP signaling pathway	BP	direct assay
activin receptor signaling pathway	BP	direct assay
atrial septum primum morphogenesis	BP	mutant phenotype
cardiac muscle cell fate commitment	BP	mutant phenotype
cellular response to BMP stimulus	BP	mutant phenotype
embryonic heart tube morphogenesis	BP	mutant phenotype
endocardial cushion cell fate commitment	BP	mutant phenotype
mitral valve morphogenesis	BP	mutant phenotype
negative regulation of G1/S transition of mitotic cell cycle	BP	mutant phenotype
negative regulation of activin receptor signaling pathway	BP	mutant phenotype
negative regulation of extrinsic apoptotic signaling pathway	BP	mutant phenotype
negative regulation of signal transduction	BP	mutant phenotype
osteoblast differentiation	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of SMAD protein signal transduction	BP	direct assay
positive regulation of bone mineralization	BP	mutant phenotype
positive regulation of cell migration	BP	genetic interaction
positive regulation of determination of dorsal identity	BP	direct assay
positive regulation of intracellular signal transduction	BP	mutant phenotype
positive regulation of osteoblast differentiation	BP	mutant phenotype
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of ossification	BP	mutant phenotype
transforming growth factor beta receptor signaling pathway	BP	direct assay
activin receptor complex	CC	direct assay
plasma membrane	CC	direct assay
ATP binding	MF	direct assay
BMP receptor activity	MF	direct assay
SMAD binding	MF	direct assay
activin binding	MF	direct assay
activin receptor activity, type I	MF	direct assay
cadherin binding	MF	physical interaction
protein homodimerization activity	MF	direct assay
protein kinase activity	MF	direct assay
protein serine/threonine kinase activity	MF	direct assay
protein tyrosine kinase binding	MF	physical interaction
transforming growth factor beta binding	MF	direct assay
transmembrane receptor protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,162 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACVR1	BMP4	P12644	871
ACVR1	SMAD9	O15198	839
ACVR1	NOG	Q13253	825
ACVR1	SMAD4	Q13485	817
ACVR1	ACRV1	P26436	800
ACVR1	SMAD5	Q99717	792
ACVR1	TGFB1	P01137	791
ACVR1	BMP2	P12643	771
ACVR1	BMP6	P22004	740
ACVR1	BMP7	P18075	716
ACVR1	ACVR2A	P27037	711
ACVR1	GDF2	Q9UK05	703
ACVR1	BMPR2	Q13873	654
ACVR1	SMAD2	Q15796	625
ACVR1	SMAD6	O43541	623
ACVR1	ACVR2B	Q13705	623

IntAct

Human interaction partners of ACVR1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
TGFBRAP1	association	0.730	1
BMPR1A	association	0.530	2
EPHA6	physical association	0.400	2
ADMP	physical association	0.400	1
TGFBR1	physical association	0.370	1
NBAS	association	0.350	1
TNFRSF10B	association	0.350	1

BioGRID (142 interactions; top human partners by supporting records): BMPR2 (Affinity Capture-MS; 6 records), BMPR1A (Affinity Capture-MS; 5 records), ACVR1B (Affinity Capture-MS; 4 records), ACVRL1 (Affinity Capture-MS; 3 records), ARV1 (Affinity Capture-MS; 3 records), GRAMD1A (Affinity Capture-MS; 3 records), PSMD14 (Affinity Capture-Western; 3 records), RNF149 (Affinity Capture-MS; 3 records), SMAD1 (PCA; 3 records), TGFBRAP1 (Affinity Capture-MS; 3 records), ACVR2A (Affinity Capture-Western; 2 records), BMP7 (Reconstituted Complex; 2 records), CD320 (Affinity Capture-MS; 2 records), LRRIQ1 (Affinity Capture-MS; 2 records), MRAP2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 15 of 16 signaling 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

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ ACVR1-ACVR2B-GDF2 complex	3	ACVR1, ACVR2B, GDF2
★ ACVR1-BMPR2-GDF2 complex	3	ACVR1, BMPR2, GDF2
★ ACVR1-BMP6-BMPR1A complex	3	ACVR1, BMP6, BMPR1A
★ ACVR1-ACVR2B receptor complex	2	ACVR1, ACVR2B
★ ACVR1-BMPR2 receptor complex	2	ACVR1, BMPR2

Ligand–receptor pairs (CellPhoneDB) (5)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

5 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ACVR1;ACVR2B		Signaling by Inhibin/Activin
ACVR1;ACVR2A		Signaling by Inhibin/Activin
ACVR1;BMPR2		Signaling by BMP
TGFBR2;ACVR1		Signaling by Transforming growth factor
AMHR2;ACVR1		Signaling by Muellerian-inhibiting factor

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for ACVR1: 459 ClinVar records (15 pathogenic / likely pathogenic); 7 CIViC cancer variants; 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	2
Uncertain significance	216
Likely benign	158
Benign	40

Top pathogenic / likely-pathogenic (15)

Showing all 15 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
18309	NM_001111067.4(ACVR1):c.617G>A (p.Arg206His)	Pathogenic	criteria provided, multiple submitters, no conflicts	25
29593	NM_001111067.4(ACVR1):c.982G>A (p.Gly328Arg)	Pathogenic	criteria provided, single submitter	3
216885	NM_001111067.4(ACVR1):c.772A>G (p.Arg258Gly)	Likely pathogenic	criteria provided, single submitter	1
60219	GRCh38/hg38 2q23.1-24.3(chr2:148917286-163204623)x1	Pathogenic	criteria provided, single submitter	1
3062503	GRCh37/hg19 2q24.1-24.3(chr2:157718631-165360287)x1	Pathogenic	criteria provided, single submitter	1
4974525	NC_000002.11:g.(153616354_154334750)_(162934546_162999874)del	Pathogenic	criteria provided, single submitter	1
236378	Single allele	Likely pathogenic	criteria provided, single submitter	1
18311	NM_001111067.4(ACVR1):c.774G>C (p.Arg258Ser)	Pathogenic	no assertion criteria provided	1
29594	NM_001111067.4(ACVR1):c.982G>T (p.Gly328Trp)	Pathogenic	no assertion criteria provided	1
29596	NM_001111067.4(ACVR1):c.1124G>C (p.Arg375Pro)	Pathogenic	no assertion criteria provided	1
29597	NM_001111067.4(ACVR1):c.605G>T (p.Arg202Ile)	Pathogenic	no assertion criteria provided	1
208843	NM_001111067.4(ACVR1):c.587T>C (p.Leu196Pro)	Pathogenic	no assertion criteria provided	1
443473	GRCh37/hg19 2q24.1-24.3(chr2:157970774-169270675)x1	Pathogenic	no assertion criteria provided	1
1340352	GRCh37/hg19 2q23.3-24.1(chr2:154328530-158759642)x1	Pathogenic	no assertion criteria provided	1
1340408	GRCh37/hg19 2q23.3-24.1(chr2:154852961-159126250)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ACVR1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,904):

Position(s)	Effect	Δscore	Sites
2:157738438–157738439	donor_loss	1.0000	5
2:157738499	donor_gain	1.0000
2:157738571–157738572	acceptor_loss	1.0000	6
2:157738579	acceptor_gain	1.0000
2:157761078–157761079	acceptor_loss	1.0000	5
2:157780438	donor_gain	1.0000
2:157780602	acceptor_loss	1.0000
2:157799425–157799426	donor_loss	1.0000	4
2:157799501–157799502	acceptor_loss	1.0000	6
2:157799503	acceptor_gain	1.0000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Colon Adenocarcinoma (validation)	unfavorable	7.38e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000195

Disease associations

OMIM: gene MIM:102576 | disease phenotypes: MIM:135100, MIM:308350

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
fibrodysplasia ossificans progressiva	Definitive	Autosomal dominant	6
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

2 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Skeletal dysplasia	green
Autosomal recessive primary hypertrophic osteoarthropathy	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

Mondo (4): fibrodysplasia ossificans progressiva (MONDO:0007606), autism spectrum disorder (MONDO:0005258), developmental and epileptic encephalopathy, 1 (MONDO:0010632), congenital heart disease (MONDO:0005453)

Orphanet (2): Fibrodysplasia ossificans progressiva (Orphanet:337), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

54 phenotypes (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	Kidney stone
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
HP:0003306	Spinal rigidity
HP:0003367	Abnormal femoral neck morphology
HP:0003468	Abnormal vertebral morphology
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004629	Small cervical vertebral bodies
HP:0005986	Limitation of neck motion
HP:0006429	Broad femoral neck
HP:0008449	Progressive cervical vertebral spine fusion
HP:0010034	Short 1st metacarpal
HP:0010054	Abnormality of the first metatarsal bone
HP:0010058	Aplasia/Hypoplasia of the phalanges of the hallux
HP:0010109	Short hallux
HP:0010566	Hamartoma
HP:0011986	Ectopic ossification
HP:0011987	Ectopic ossification in muscle tissue
HP:0011988	Ectopic ossification in tendon tissue
HP:0011989	Ectopic ossification in ligament tissue
HP:0030038	Enchondroma
HP:0030084	Clinodactyly
HP:0030431	Osteochondroma
HP:0030838	Hip pain
HP:0100240	Synostosis of joints
HP:6000952	Delayed toe phalanx ossification

GWAS associations

5 associations:

Study	Trait	p-value
GCST90020024_1270	A body shape index	6e-11
GCST90020027_1206	Waist-hip index	1e-10
GCST90020025_150	Waist-to-hip ratio adjusted for BMI	3e-10
GCST90020029_418	Waist circumference adjusted for body mass index	3e-9
GCST004198_3	Severe gingival inflammation	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ACVR1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

4 curated-mechanism drugs:

Drug	Modality	Max phase
DIBOTERMIN ALFA	Protein	4
EPTOTERMIN ALFA	Protein	4
MOMELOTINIB DIHYDROCHLORIDE MONOHYDRATE	Small molecule	4
PACRITINIB CITRATE	Small molecule	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 155,580 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

39 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1078178	MOMELOTINIB	4	3,649
CHEMBL2035187	PACRITINIB	4	3,544
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL5416410	DASATINIB	4	674
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL3286830	LORLATINIB	4	3,833
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL24828	VANDETANIB	4	43,290
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL31965	CANERTINIB	3	8,307
CHEMBL491473	CEDIRANIB	3	9,464
CHEMBL1879463	DACTOLISIB	3	8,349
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL603469	LESTAURTINIB	3
CHEMBL217092	SARACATINIB	3	4,089
CHEMBL587723	AEE-788	2	2,800
CHEMBL495727	AT-9283	2	1,442
CHEMBL1967878	CENISERTIB	2	373
CHEMBL402548	DANUSERTIB	2	2,036
CHEMBL1980297	ILORASERTIB	2
CHEMBL5956963	KER-047	2
CHEMBL564829	MILCICLIB	2
CHEMBL253969	OSI-632	2
CHEMBL475251	R-406	2
CHEMBL3544964	RAVOXERTINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL5314579	ZILURGISERTIB	2
CHEMBL551064	AEW-541	1
CHEMBL482967	CYC-116	1
CHEMBL1090479	GSK-1070916	1
CHEMBL1908397	KW-2449	1
CHEMBL3600873	MK-5108	1
CHEMBL49120	PD-0166285	1
CHEMBL1980391	RG-1530	1
CHEMBL1952329	SGI-1776	1
CHEMBL3544932	TAK-901	1
CHEMBL3545085	XL-228	1

Clinical evidence (CIViC)

Drug × variant × indication, from 3 curated evidence items; also 10 diagnostic, 1 prognostic, 1 predisposing. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

3 predictive associations by evidence level:

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

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

1 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
ACVR1 G328V	Diffuse Midline Glioma, H3 K27-altered		Diagnostic	Tier II - Level C	Positive

CIViC curated variants (7)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

G328V (missense variant), Gain-of-Function, G328W (missense variant), G328E (gain of function variant,missense variant), Mutation, R206H, G356D.

PharmGKB: 1 entry (CPIC guideline: no)

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)

820 measured of 1407 human assays (1409 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
6-[2-(6-methyl-2-pyridinyl)pyrazol-3-yl]imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20230303562: PYRAZOLE COMPOUND AND PREPARATION METHOD THEREFOR AND USE THEREOF
CHEMBL4790396	IC50	1 nM
K02288a	IC50	1.1 nM
N-(4-(4-(2- Methoxyethyl)piperazin- 1-yl)phenyl)-4-(3- (pyridin-3-yl)-1- (tetrahydrofuran-3- yl)-1H-pyrazol-4- yl)pyrimidin-2-amine	IC50	1.3 nM	US-10954216: BMP-signal-inhibiting compound
Staurosporine	KD	1.7 nM
CHEMBL5630864	IC50	2 nM
CHEMBL5630109	IC50	2 nM
7-[2-(6-methyl-2-pyridinyl)pyrazol-3-yl]imidazo[1,2-b]pyridazine	IC50	2.36 nM	US-20230303562: PYRAZOLE COMPOUND AND PREPARATION METHOD THEREFOR AND USE THEREOF
N-(4-(1-Ethyl-3- (pyridin-3-yl)-1H- pyrazol-4- yl)pyrimidin-2-yl)-2- methyl-1,2,3,4- tetrahydroisoquinolin- 6-amine	IC50	2.7 nM	US-10954216: BMP-signal-inhibiting compound
N-(4-(4-Amino-4- ethylpiperidin-1- yl)phenyl)-4-(1-ethyl- 3-(pyridin-3-yl)-1H- pyrazol-4- yl)pyrimidin-2-amine	IC50	3 nM	US-10954216: BMP-signal-inhibiting compound
CHEMBL4526828	IC50	3 nM
CHEMBL5630025	IC50	3 nM
4-[6-(methoxymethyl)-7-(4-piperazin-1-ylphenyl)imidazo[1,2-b]pyridazin-3-yl]quinoline	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[4-[6-methyl-3-(7-pyridin-4-ylquinolin-4-yl)imidazo[1,2-b]pyridazin-7-yl]pyrazol-1-yl]cyclohexan-1-ol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
(4-methylpiperazin-1-yl)-[4-[6-methyl-3-(7-pyridin-4-ylquinolin-4-yl)imidazo[1,2-b]pyridazin-7-yl]phenyl]methanone	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[7-[3-fluoro-4-[[(2R)-2-methylpyrrolidin-1-yl]methyl]phenyl]-6-methylimidazo[1,2-b]pyridazin-3-yl]-7-pyridin-4-ylquinoline	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
N-methyl-4-[6-methyl-7-(4-piperazin-1-ylphenyl)imidazo[1,2-b]pyridazin-3-yl]quinoline-7-carboxamide	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[6-methyl-7-(4-piperazin-1-ylphenyl)imidazo[1,2-b]pyridazin-3-yl]-7-(1-methylpyrazol-3-yl)quinoline	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
[4-[4-[6-methyl-7-(4-piperazin-1-ylphenyl)imidazo[1,2-b]pyridazin-3-yl]quinolin-7-yl]-2-pyridinyl]methanol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[4-[6-methyl-7-(4-piperazin-1-ylphenyl)imidazo[1,2-b]pyridazin-3-yl]quinolin-7-yl]morpholine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
(3,5-difluorophenyl)-[4-[6-methyl-7-(4-piperazin-1-ylphenyl)imidazo[1,2-b]pyridazin-3-yl]quinolin-7-yl]methanol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[6-methyl-7-(1-piperidin-4-ylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]quinoline	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[7-(1-ethylpyrazol-4-yl)-6-methylimidazo[1,2-b]pyridazin-3-yl]-2-pyridin-2-yl-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[4-[6-methyl-3-(7-pyrazin-2-yl-1,8-naphthyridin-4-yl)imidazo[1,2-b]pyridazin-7-yl]pyrazol-1-yl]cyclohexan-1-ol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[7-[4-(azetidin-1-ylmethyl)phenyl]-6-methylimidazo[1,2-b]pyridazin-3-yl]-2-pyrazin-2-yl-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[6-methyl-7-(1-propan-2-ylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-2-pyrazin-2-yl-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[6-methyl-7-[1-(oxan-4-yl)pyrazol-4-yl]imidazo[1,2-b]pyridazin-3-yl]-2-pyrazin-2-yl-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[6-methyl-7-(1-propan-2-ylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-2-(1-methylpyrazol-3-yl)-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
N,N-dimethyl-4-[6-methyl-3-[7-(1-methylpyrazol-3-yl)-1,8-naphthyridin-4-yl]imidazo[1,2-b]pyridazin-7-yl]benzamide	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
2-(1-methylimidazol-4-yl)-5-[6-methyl-7-(1-propan-2-ylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[[4-[3-[7-(1-ethylimidazol-4-yl)-1,8-naphthyridin-4-yl]-6-methylimidazo[1,2-b]pyridazin-7-yl]phenyl]methyl]morpholine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
2-(1-ethylimidazol-4-yl)-5-[6-methyl-7-(1-propan-2-ylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[7-[4-(azetidin-1-ylmethyl)phenyl]-6-methylimidazo[1,2-b]pyridazin-3-yl]-2-(1-ethylimidazol-4-yl)-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[7-[4-[(3,3-difluoroazetidin-1-yl)methyl]phenyl]-6-methylimidazo[1,2-b]pyridazin-3-yl]-2-(1-ethylimidazol-4-yl)-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
[(2S)-4-[[4-[3-[7-(1-ethylimidazol-4-yl)-1,8-naphthyridin-4-yl]-6-methylimidazo[1,2-b]pyridazin-7-yl]phenyl]methyl]morpholin-2-yl]methanol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[6-methyl-7-[4-(pyrrolidin-1-ylmethyl)phenyl]imidazo[1,2-b]pyridazin-3-yl]-2-(4-methyltriazol-2-yl)-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[6-methyl-7-(1-propan-2-ylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-2-(4-methyltriazol-2-yl)-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
N,N-dimethyl-1-[4-[6-methyl-3-[7-(4-methyltriazol-2-yl)-1,8-naphthyridin-4-yl]imidazo[1,2-b]pyridazin-7-yl]phenyl]methanamine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
4-[[4-[6-methyl-3-[7-(4-methyltriazol-2-yl)-1,8-naphthyridin-4-yl]imidazo[1,2-b]pyridazin-7-yl]phenyl]methyl]morpholine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
3-methyl-1-[[4-[6-methyl-3-[7-(4-methyltriazol-2-yl)-1,8-naphthyridin-4-yl]imidazo[1,2-b]pyridazin-7-yl]phenyl]methyl]azetidin-3-ol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
5-[6-methyl-7-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]imidazo[1,2-b]pyridazin-3-yl]-2-(4-methyltriazol-2-yl)-1,8-naphthyridine	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
1-[[4-[3-[7-(1-ethylimidazol-4-yl)-1,8-naphthyridin-4-yl]-6-methylimidazo[1,2-b]pyridazin-7-yl]phenyl]methyl]piperidin-4-ol	IC50	3 nM	US-11459329: Imidazopyridazine and imidazopyridine compounds and uses thereof
CEP-701	KD	3.4 nM
CHEMBL5591770	IC50	3.9 nM
2-({4-[2-(diethylamino)ethoxy]phenyl}amino)-8-ethyl-6-phenyl-7H,8H-pyrido[2,3-d]pyrimidin-7-one	IC50	4 nM
CHEMBL4434694	IC50	4 nM
6-[2-(6-methyl-2-pyridinyl)pyrazol-3-yl]-[1,2,4]triazolo[4,3-a]pyridine-3-carboxamide	IC50	4.82 nM	US-20230303562: PYRAZOLE COMPOUND AND PREPARATION METHOD THEREFOR AND USE THEREOF
CHEMBL4784430	IC50	5 nM
CHEMBL4776631	IC50	5 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

536 with measured affinity, of 1193 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
Particulate Matter	increases expression, decreases expression, increases abundance	4
bisphenol A	increases expression, increases methylation, affects expression	3
sodium arsenite	increases expression, increases methylation	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cyclosporine	increases expression	3
Air Pollutants	increases expression, decreases expression, increases abundance	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	decreases expression, increases abundance	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)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00668824	Phase 4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	Phase 4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	Phase 4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	Phase 4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	Phase 4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	Phase 4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	Phase 4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	Phase 4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	Phase 4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	Phase 4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	Phase 4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	Phase 4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT03312634	Phase 3	COMPLETED	An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.
NCT05027802	Phase 3	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	Phase 3	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	Phase 3	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	Phase 3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	Phase 3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	Phase 3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	Phase 3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	Phase 3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	Phase 3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	Phase 3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	Phase 3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	Phase 3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	Phase 3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	Phase 3	UNKNOWN	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	Phase 3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	Phase 3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	Phase 3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	Phase 3	RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT02190747	Phase 2	COMPLETED	An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects
NCT02279095	Phase 2	COMPLETED	An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
NCT02521792	Phase 2	TERMINATED	In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects
NCT03188666	Phase 2	COMPLETED	A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva
NCT04307953	Phase 2	ACTIVE_NOT_RECRUITING	Saracatinib Trial TO Prevent FOP
NCT05039515	Phase 2	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	Phase 2	RECRUITING	To Assess the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva
NCT00115375	Phase 2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	Phase 2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	Phase 2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	Phase 2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	Phase 2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	Phase 2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	Phase 2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	Phase 2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	Phase 2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	Phase 2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	Phase 2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	Phase 2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	Phase 2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE
NCT01841177	Phase 2	COMPLETED	Evaluating Precision of Therapy - Milrinone
NCT02046135	Phase 2	TERMINATED	Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery
NCT02133573	Phase 2	COMPLETED	Randomized Trial of Maternal Progesterone Therapy
NCT02232399	Phase 2	COMPLETED	Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
NCT02492269	Phase 2	COMPLETED	Stress Response and Neurodevelopmental Outcome After Cardiac Surgery Utilizing CPB in Children: A Prospective, Double Blinded and Randomized Study
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACVR1 across ~30M SureChEMBL compounds — explore on Sugi Predict.