ACVRL1
activin A receptor like type 1, the group of Type 1 receptor serine/threonine kinases
Basic information
Region (hg38): 12:51906908-51923361
Previous symbols: [ "ACVRLK1", "ORW2" ]
Links
Phenotypes
GenCC
Source:
- telangiectasia, hereditary hemorrhagic, type 2 (Strong), mode of inheritance: AD
- hereditary hemorrhagic telangiectasia (Supportive), mode of inheritance: AD
- telangiectasia, hereditary hemorrhagic, type 2 (Strong), mode of inheritance: AD
- telangiectasia, hereditary hemorrhagic, type 2 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Telangiectasia, hereditary hemorrhagic, type 2 | AD | Cardiovascular; Gastrointestinal; Hematologic; Obstetric; Pharmacogenomic; Pulmonary | There are a number of surveillance/preventive/treatment based measures; These include: epistaxis treatment with humidification, lubricants, hormone therapy, anti-fibrinolytic agents, ablation, surgery, etc.; GI bleeding: iron replacement, hormonal or anti-fibrinolytic medication, surgery, etc.; Pulmonary AVM: catheter occlusion, and preventive measures such as antibiotic prophylaxis; symptomatic cerebral AVMs: surgery/embolotherapy, etc; Severe hepatic AVMs: liver transplantation if medical management fails; Specific pregnancy-related screening may be indicated; Anemia: Iron replacement or transfusion; Avoidance of certain activities and use of anticoagulant and anti-inflammatory agents (including aspirin) in the case of significant bleeding; For PAH, medical therapy (eg, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, but lung transplantation may be indicated | Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Pulmonary | 5037289; 3186989; 8640225; 10946360; 9354504; 11170071; 11484689; 14684682; 16470787; 16155196; 6542389; 17786384; 18498373; 18831062; 18312453; 19439755; 20056902; 20301525 |
ClinVar
This is a list of variants' phenotypes submitted to
- Telangiectasia, hereditary hemorrhagic, type 2 (229 variants)
- Cardiovascular phenotype (108 variants)
- not provided (45 variants)
- Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia (9 variants)
- not specified (7 variants)
- Pulmonary arterial hypertension (4 variants)
- Pulmonary hypertension, primary, 1 (3 variants)
- Telangiectasia, hereditary hemorrhagic, type 1 (3 variants)
- Hereditary hemorrhagic telangiectasia (2 variants)
- ACVRL1-related disorder (2 variants)
- Pulmonary arterial hypertension;Epistaxis (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACVRL1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 120 | 125 | ||||
| missense | 70 | 120 | 137 | 11 | 339 | |
| nonsense | 63 | 67 | ||||
| start loss | 0 | |||||
| frameshift | 118 | 14 | 133 | |||
| inframe indel | 11 | 18 | ||||
| splice donor/acceptor (+/-2bp) | 22 | 16 | 38 | |||
| splice region | 1 | 4 | 12 | 9 | 1 | 27 |
| non coding | 40 | 51 | 68 | 161 | ||
| Total | 277 | 159 | 191 | 182 | 72 |
Highest pathogenic variant AF is 0.0000131
Variants in ACVRL1
This is a list of pathogenic ClinVar variants found in the ACVRL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-51907469-G-C | Telangiectasia, hereditary hemorrhagic, type 2 | Benign (Jan 15, 2019) | ||
| 12-51907499-C-G | Telangiectasia, hereditary hemorrhagic, type 2 | Likely benign (Jan 13, 2018) | ||
| 12-51907507-A-C | Telangiectasia, hereditary hemorrhagic, type 2 | Uncertain significance (Jan 13, 2018) | ||
| 12-51907533-G-C | Telangiectasia, hereditary hemorrhagic, type 2 | Uncertain significance (Jan 13, 2018) | ||
| 12-51907572-G-A | Telangiectasia, hereditary hemorrhagic, type 2 | Uncertain significance (Sep 01, 2021) | ||
| 12-51907643-G-A | Telangiectasia, hereditary hemorrhagic, type 2 | Uncertain significance (Jan 13, 2018) | ||
| 12-51907649-G-A | Telangiectasia, hereditary hemorrhagic, type 2 | Conflicting classifications of pathogenicity (Aug 01, 2024) | ||
| 12-51907655-C-G | not specified • Telangiectasia, hereditary hemorrhagic, type 2 | Benign (Dec 05, 2021) | ||
| 12-51912002-C-T | Benign (Jun 26, 2018) | |||
| 12-51912005-A-G | Benign (Jun 26, 2018) | |||
| 12-51912243-C-G | Telangiectasia, hereditary hemorrhagic, type 2 | Benign (Dec 05, 2021) | ||
| 12-51912411-C-T | Telangiectasia, hereditary hemorrhagic, type 2 | Uncertain significance (Jan 06, 2019) | ||
| 12-51912437-C-T | not specified • Telangiectasia, hereditary hemorrhagic, type 2 | Benign (Nov 29, 2023) | ||
| 12-51912453-C-T | Likely benign (Jul 01, 2023) | |||
| 12-51912471-G-T | Uncertain significance (Jun 01, 2017) | |||
| 12-51912479-C-T | Telangiectasia, hereditary hemorrhagic, type 2 | Uncertain significance (Nov 14, 2023) | ||
| 12-51912483-G-A | Telangiectasia, hereditary hemorrhagic, type 2 | Conflicting classifications of pathogenicity (Jan 04, 2024) | ||
| 12-51912487-T-TC | Cardiovascular phenotype | Pathogenic (Jul 11, 2018) | ||
| 12-51912492-C-G | Telangiectasia, hereditary hemorrhagic, type 2 • Cardiovascular phenotype | Likely benign (May 12, 2021) | ||
| 12-51912498-A-G | Telangiectasia, hereditary hemorrhagic, type 2 | Likely benign (Aug 06, 2020) | ||
| 12-51912510-GC-G | Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia | Pathogenic (-) | ||
| 12-51912514-C-CT | Telangiectasia, hereditary hemorrhagic, type 2 | Pathogenic (Jul 03, 2017) | ||
| 12-51912516-G-C | Cardiovascular phenotype | Likely benign (Jul 01, 2021) | ||
| 12-51912522-C-CT | Telangiectasia, hereditary hemorrhagic, type 2 | Pathogenic (Aug 14, 2021) | ||
| 12-51912528-G-GA | Telangiectasia, hereditary hemorrhagic, type 2 | Likely pathogenic (Jul 23, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ACVRL1 | protein_coding | protein_coding | ENST00000388922 | 9 | 16454 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000967 | 0.997 | 125733 | 0 | 12 | 125745 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.45 | 190 | 311 | 0.610 | 0.0000209 | 3227 |
| Missense in Polyphen | 57 | 153.08 | 0.37236 | 1576 | ||
| Synonymous | -0.449 | 145 | 138 | 1.05 | 0.00000978 | 1030 |
| Loss of Function | 2.66 | 9 | 22.7 | 0.397 | 0.00000108 | 243 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000126 | 0.000123 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000795 | 0.0000791 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000343 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well. {ECO:0000269|PubMed:22718755, ECO:0000269|PubMed:22799562, ECO:0000269|PubMed:26176610}.;
- Disease
- DISEASE: Telangiectasia, hereditary hemorrhagic, 2 (HHT2) [MIM:600376]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269|PubMed:10694922, ECO:0000269|PubMed:10767348, ECO:0000269|PubMed:11170071, ECO:0000269|PubMed:11484689, ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:15024723, ECO:0000269|PubMed:15712270, ECO:0000269|PubMed:16525724, ECO:0000269|PubMed:16752392, ECO:0000269|PubMed:20414677, ECO:0000269|PubMed:26176610, ECO:0000269|PubMed:8640225, ECO:0000269|PubMed:9245985}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- TGF-Core;Signal Transduction;TGF-beta super family signaling pathway canonical;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;BMP2 signaling TGF-beta MV;VEGF;Signaling by BMP;Signaling by TGF-beta family members;ALK1 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.441
Intolerance Scores
- loftool
- 0.0783
- rvis_EVS
- -1.02
- rvis_percentile_EVS
- 8
Haploinsufficiency Scores
- pHI
- 0.930
- hipred
- Y
- hipred_score
- 0.524
- ghis
- 0.577
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Acvrl1
- Phenotype
- growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype;
Zebrafish Information Network
- Gene name
- acvrl1
- Affected structure
- endothelial cell
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- angiogenesis;response to hypoxia;in utero embryonic development;regulation of endothelial cell proliferation;negative regulation of endothelial cell proliferation;positive regulation of endothelial cell proliferation;lymphangiogenesis;blood vessel maturation;blood vessel remodeling;blood vessel endothelial cell proliferation involved in sprouting angiogenesis;endocardial cushion morphogenesis;regulation of DNA replication;regulation of transcription, DNA-templated;protein phosphorylation;negative regulation of cell adhesion;signal transduction;transforming growth factor beta receptor signaling pathway;pattern specification process;blood circulation;regulation of blood pressure;negative regulation of cell population proliferation;negative regulation of endothelial cell migration;negative regulation of gene expression;positive regulation of pathway-restricted SMAD protein phosphorylation;negative regulation of cell growth;negative regulation of cell migration;BMP signaling pathway;positive regulation of BMP signaling pathway;positive regulation of chondrocyte differentiation;activin receptor signaling pathway;wound healing, spreading of epidermal cells;dorsal aorta morphogenesis;regulation of blood vessel endothelial cell migration;negative regulation of blood vessel endothelial cell migration;negative regulation of endothelial cell differentiation;positive regulation of endothelial cell differentiation;positive regulation of angiogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of focal adhesion assembly;lymphatic endothelial cell differentiation;artery development;venous blood vessel development;endothelial tube morphogenesis;retina vasculature development in camera-type eye;cellular response to transforming growth factor beta stimulus;cellular response to BMP stimulus;endocardial cushion to mesenchymal transition;negative regulation of DNA biosynthetic process
- Cellular component
- plasma membrane;integral component of plasma membrane;cell surface;dendrite;neuronal cell body;receptor complex;activin receptor complex
- Molecular function
- protein serine/threonine kinase activity;transmembrane receptor protein serine/threonine kinase activity;transforming growth factor beta-activated receptor activity;transforming growth factor beta receptor activity, type I;protein binding;ATP binding;activin receptor activity, type I;growth factor binding;protein kinase binding;SMAD binding;metal ion binding;activin binding;transforming growth factor beta binding;BMP receptor activity