ACVRL1
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ACVRL1 (HGNC:175) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
activin A receptor like type 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
ACVRLK1, ORW2
Alias symbols
HHT2, ALK1, HHT
%HI
49.42(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.51(Read more about gnomAD pLI score)
LOEUF
0.57(Read more about gnomAD LOEUF score)
Cytoband
12q13.13
Genomic Coordinates
GRCh37/hg19: chr12:52301288-52317145 NCBI Ensembl UCSC
GRCh38/hg38: chr12:51906944-51923361 NCBI Ensembl UCSC
MANE Select Transcript
NM_000020.3 ENST00000388922.9 (Read more about MANE Select)
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:2617... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-21934
ClinGen Curation ID:
CCID:006618
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
11/10/2016

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • telangiectasia, hereditary hemorrhagic, type 2 Monarch
HI Evidence:
  • PUBMED: 18312453
    Shoukier et al (2008) documented two cases in which large deletions encompassing the entire ACVRL1 gene cause hemorrhagic telangiectasia
  • PUBMED: 20414677
    Richards-Yutz et al 2010 provided a review of the molecular diagnosis of HHT in a series of 600 individuals. Approximately one third of pathogenic variants in ACVRL1 are functionally null alleles.
HI Evidence Comments:
ACVRL1 encodes Activin A receptor, type II-like kinase 1, a cell-surface receptor for the TGF-beta superfamily of ligands that functions in endothelial tissues to regulate signal transduction during vascular morphogenesis. Pathogenic variants in the ACVRL1 gene cause autosomal dominant hereditary hemorrhagic telangiectasia (HHT), a vascular malformation disorder characterized clinically by recurrent epistaxis (nosebleeds), cutaneous or mucosal telangiectases, and visceral arteriovenous malformations that may lead to symptoms when they occur in the brain, liver, or lungs. Age of onset for HHT symptoms is generally in adolescence or adulthood, although cases of early, severe onset have been reported (see GeneReviews). It is suspected due to the possibility of late-onset HHT that this condition continues to be underdiagnosed. This likely contributes to the presence of individuals in population databases such as ExAC that harbor apparent loss-of-function ACVRL1 variants, although this gene is not thought to be loss-of-function tolerant. Genotype-phenotype correlation has not been well established for different classes of ACVRL1 variants, and extremely variable expressivity of HTT symptoms can be observed even within a family carrying the same pathogenic ACVRL1 variant. Most pathogenic ACVRL1 variants are sequence-level changes, although Shoukier et al. documented two cases in which large deletions encompassing the entire ACVRL1 gene cause HHT (Shoukier 2008). Approximately one third of pathogenic variants in ACVRL1 are functionally null alleles (Richards-Yutz et al 2010).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)