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mutLBSgeneDB |
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| Gene summary for ACVR1 |
 Gene summary |
| Basic gene Info. | Gene symbol | ACVR1 |
| Gene name | activin A receptor, type I | |
| Synonyms | ACTRI|ACVR1A|ACVRLK2|ALK2|FOP|SKR1|TSRI | |
| Cytomap | UCSC genome browser: 2q23-q24 | |
| Type of gene | protein-coding | |
| RefGenes | NM_001105.4, NM_001111067.2, | |
| Description | TGF-B superfamily receptor type Iactivin A receptor, type II-like kinase 2activin receptor type Iactivin receptor type-1activin receptor-like kinase 2hydroxyalkyl-protein kinaseserine/threonine-protein kinase receptor R1 | |
| Modification date | 20141222 | |
| dbXrefs | MIM : 102576 | |
| HGNC : HGNC | ||
| Ensembl : ENSG00000115170 | ||
| HPRD : 00021 | ||
| Vega : OTTHUMG00000131967 | ||
| Protein | UniProt: Q04771 go to UniProt's Cross Reference DB Table | |
| Expression | CleanEX: HS_ACVR1 | |
| BioGPS: 90 | ||
| Pathway | NCI Pathway Interaction Database: ACVR1 | |
| KEGG: ACVR1 | ||
| REACTOME: ACVR1 | ||
| Pathway Commons: ACVR1 | ||
| Context | iHOP: ACVR1 | |
| ligand binding site mutation search in PubMed: ACVR1 | ||
| UCL Cancer Institute: ACVR1 | ||
| Assigned class in mutLBSgeneDB | A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes. | |
| References showing study about ligand binding site mutation for ACVR1. | 1. "Haupt J, Deichsel A, Stange K, Ast C, Bocciardi R, Ravazzolo R, Di Rocco M,Ferrari P, Landi A, Kaplan FS, Shore EM, Reissner C, Seemann P. ACVR1 p.Q207E causes classic fibrodysplasia ossificans progressiva and is functionally distinct from the engineered constitutively active ACVR1 p.Q207D variant. Hum Mol Genet. 2014 Oct 15;23(20):5364-77. doi: 10.1093/hmg/ddu255. Epub 2014 May 22. PubMed PMID: 24852373; PubMed Central PMCID: PMC4168825. " 24852373 2. "Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, Wen X, Nannuru KC,Jimenez J, Xie L, Das N, Makhoul G, Chernomorsky R, D'Ambrosio D, Corpina RA,Schoenherr CJ, Feeley K, Yu PB, Yancopoulos GD, Murphy AJ, Economides AN. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 2015 Sep 2;7(303):303ra137. doi: 10.1126/scitranslmed.aac4358. PubMed PMID: 26333933." 26333933 | |
| Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez |
| GO ID | GO Term | PubMed ID | GO:0006468 | protein phosphorylation | 12065756 | GO:0007179 | transforming growth factor beta receptor signaling pathway | 8242742 | GO:0010862 | positive regulation of pathway-restricted SMAD protein phosphorylation | 19506109 | GO:0018107 | peptidyl-threonine phosphorylation | 19736306 | GO:0030509 | BMP signaling pathway | 18436533 | GO:0032924 | activin receptor signaling pathway | 19506109 | GO:0045893 | positive regulation of transcription, DNA-templated | 8242742 | GO:0045944 | positive regulation of transcription from RNA polymerase II promoter | 19506109 | GO:0060389 | pathway-restricted SMAD protein phosphorylation | 19736306 | GO:2000017 | positive regulation of determination of dorsal identity | 19506109 |
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| Ligand binding site mutations for ACVR1 |
| Lollipop-style diagram of mutations at LBS in amino-acid sequence. We represented ligand binding site mutations only. (You can see big image via clicking.)  : non-synonymous mutation on LBS, Circle size denotes number of samples. |
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| Cancer type specific mutLBS sorted by frequency |
| LBS | AAchange of nsSNV | Cancer type | # samples | S290 | S290L | COAD | 2 | N341 | N341I | COAD | 1 | E248 | R247K | LUAD | 1 | E287 | E287K | LUAD | 1 | D354 | G356D | UCEC | 1 |
| cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma. |
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| Protein structure related information for ACVR1 |
| Relative protein structure stability change (ΔΔE) using Mupro 1.1 Mupro score denotes assessment of the effect of mutations on thermodynamic stability. (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability) |
 : nsSNV at non-LBS : nsSNV at LBS |
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| nsSNVs sorted by the relative stability change of protein structure by each mutation Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene. |
| LBS | AAchange of nsSNV | Relative stability change | E287 | E287K | -1.2818796 | E248 | R247K | -0.97348155 | D354 | G356D | -0.86469845 | S290 | S290L | -0.41870914 | N341 | N341I | -0.08143036 |
| (MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132) |
| Structure image for ACVR1 from PDB |
| PDB ID | PDB title | PDB structure | 4BGG | Crystal structure of the ACVR1 kinase in complex with LDN-213844 |  |
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| Differential gene expression and gene-gene network for ACVR1 |
| Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types |
| Differential co-expressed gene network based on protein-protein interaction data (CePIN) |
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| Phenotype information for ACVR1 |
| Gene level disease information (DisGeNet) |
| Disease ID | Disease name | # PubMed | Association type |
| umls:C0016037 | Fibrodysplasia Ossificans Progressiva | 44 | Biomarker, GeneticVariation |
| umls:C0017638 | Glioma | 3 | Biomarker |
| umls:C0027122 | Myositis Ossificans | 1 | Biomarker, GeneticVariation |
| umls:C0004114 | Astrocytoma | 1 | Biomarker |
| umls:C0242488 | Acute Lung Injury | 1 | Biomarker |
| umls:C1458155 | Breast Neoplasms | 1 | Biomarker |
| umls:C0017661 | Glomerulonephritis, IGA | 1 | Biomarker |
| Mutation level pathogenic information (ClinVar annotation) |
| Allele ID | AA change | Clinical significance | Origin | Phenotype IDs |
| 33349 | G356D | Pathogenic | Germline | MedGen:C0016037 OMIM:135100 Orphanet:ORPHA337 SNOMED CT:82725007 |
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| Pharmacological information for ACVR1 |
| Gene expression profile of anticancer drug treated cell-lines (CCLE) Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient. |
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| Gene-centered drug-gene interaction network |
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| Drug information targeting mutLBSgene (Approved drugs only) |
| Drug status | DrugBank ID | Name | Type | Drug structure |
| Approved|nutraceutical | DB00171 | Adenosine triphosphate | Small molecule |  |
| Experimental | DB08597 | 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine | Small molecule |  |
| Gene-centered ligand-gene interaction network |
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| Ligands binding to mutated ligand binding site of ACVR1 go to BioLip |
| Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS | 844 | 1-{4-[5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL] PHENYL}PIPERAZINE | 4bgg | D | E248 N341 | A3F | 3-[6-AMINO-5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL]PHENOL | 3mtf | B | E248 N341 D354 | 844 | 1-{4-[5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL] PHENYL}PIPERAZINE | 4bgg | A | E248 N341 D354 | 844 | 1-{4-[5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL] PHENYL}PIPERAZINE | 4bgg | B | E248 N341 D354 | 844 | 1-{4-[5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL] PHENYL}PIPERAZINE | 4bgg | C | E248 N341 D354 | A3F | 3-[6-AMINO-5-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-3-YL]PHENOL | 3mtf | A | E248 S290 N341 D354 | TAK | DORSOMORPHIN | 3h9r | A | E287 | TAK | DORSOMORPHIN | 4c02 | A | E287 D354 | LDN | 4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE | 3q4u | A | E287 N341 | LDN | 4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE | 3q4u | B | E287 N341 | LDN | 4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE | 3q4u | C | E287 N341 | LDN | 4-[6-(4-PIPERAZIN-1-YLPHENYL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]QUINOLINE | 3q4u | D | E287 N341 | 507 | 1-{3-[6-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)IMIDAZO[1,2-B]PYRIDAZIN-3-YL]PHENYL}ETHANONE | 3oom | A | N341 D354 | IYZ | IMIDAZOPYRIDAZIN 1 | 4dym | A | S290 |
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| Conservation information for LBS of ACVR1 |
| Multiple alignments for Q04771 in multiple species |
| LBS | AA sequence | # species | Species | A233 | QGENVAVKIFS | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | A353 | GQCCIADLGLA | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | D293 | MGSLYDYLQLT | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | D354 | QCCIADLGLAV | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | E212 | QITLLECVGKG | 3 | Homo sapiens, Rattus norvegicus, Mus musculus | E212 | QITLVECVGKG | 1 | Gallus gallus | E248 | KSWFRETELYN | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | E287 | ITHYHEMGSLY | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | G289 | HYHEMGSLYDY | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | H284 | LWLITHYHEMG | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | H286 | LITHYHEMGSL | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | K235 | ENVAVKIFSSR | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | K340 | RDLKSKNILVK | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | L263 | RHENILGFIAS | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | L281 | STQLWLITHYH | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | L343 | KSKNILVKKNG | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | N341 | DLKSKNILVKK | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | S290 | YHEMGSLYDYL | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | T283 | QLWLITHYHEM | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | V214 | TLLECVGKGRY | 3 | Homo sapiens, Rattus norvegicus, Mus musculus | V214 | TLVECVGKGRY | 1 | Gallus gallus | V222 | GRYGEVWRGSW | 3 | Homo sapiens, Rattus norvegicus, Mus musculus | V222 | GRYGEVWRGQW | 1 | Gallus gallus | Y219 | VGKGRYGEVWR | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus | Y285 | WLITHYHEMGS | 4 | Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus |
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