ACVRL1 activin A receptor like type 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACVRL1provided by HGNC
Official Full Name: activin A receptor like type 1provided by HGNC
Primary source: HGNC:HGNC:175
See related: Ensembl:ENSG00000139567 MIM:601284; AllianceGenome:HGNC:175
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HHT; ALK1; HHT2; ORW2; SKR3; ALK-1; TSR-I; ACVRLK1
Summary: This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2. [provided by RefSeq, Jul 2008]
Expression: Broad expression in placenta (RPKM 37.6), lung (RPKM 28.7) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.13

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (51906944..51923361)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (51870516..51886934)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (52301288..52317145)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development.
Title: Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development.
ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization.
Title: ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization.
Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.
Title: Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.
Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia: Experience from an HHT Center of Excellence.
Title: Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia: Experience from an HHT Center of Excellence.
Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils.
Title: Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils.
Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier Integrity in Patients With Crohn's Disease.
Title: Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier Integrity in Patients With Crohn's Disease.
ALK1 regulates the internalization of endoglin and the type III TGF-beta receptor.
Title: ALK1 regulates the internalization of endoglin and the type III TGF-β receptor.
OTULIN allies with LUBAC to govern angiogenesis by editing ALK1 linear polyubiquitin.
Title: OTULIN allies with LUBAC to govern angiogenesis by editing ALK1 linear polyubiquitin.
The clinical and genetic features of hereditary haemorrhagic telangiectasia (HHT) in central South Africa-three novel pathogenic variants.
Title: The clinical and genetic features of hereditary haemorrhagic telangiectasia (HHT) in central South Africa-three novel pathogenic variants.
The Stratified Population Screening of Hereditary Hemorrhagic Telangiectasia.
Title: The Stratified Population Screening of Hereditary Hemorrhagic Telangiectasia.

Submit: New GeneRIF Correction See all GeneRIFs (140)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Telangiectasia, hereditary hemorrhagic, type 2 MedGen: C1838163 OMIM: 600376 GeneReviews: Hereditary Hemorrhagic Telangiectasia	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2016-11-10) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2016-11-10) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-T96544 (e-PCR)
- UniSTS:51229

RH46550 (e-PCR)
- UniSTS:13612

D12S1677 (e-PCR), detects polymorphism
- UniSTS:27267

STS-T96544 (e-PCR)
- UniSTS:21126

D12S2187 (e-PCR)
- UniSTS:474532

D12S2188 (e-PCR)
- UniSTS:474533

D12S2190 (e-PCR)
- UniSTS:474534

D12S2189 (e-PCR)
- UniSTS:474535

G64249 (e-PCR)
- UniSTS:166635

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables BMP receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables BMP receptor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables BMP receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables SMAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables SMAD binding	IDA Inferred from Direct Assay more info	PubMed
enables activin binding	IDA Inferred from Direct Assay more info	PubMed
enables activin receptor activity, type I	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables transforming growth factor beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables transforming growth factor beta receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transforming growth factor beta receptor activity, type I	IBA Inferred from Biological aspect of Ancestor more info
enables transforming growth factor beta receptor activity, type I	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein serine/threonine kinase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in BMP signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in BMP signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in activin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in artery development	ISS Inferred from Sequence or Structural Similarity more info
involved_in blood circulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in blood vessel endothelial cell proliferation involved in sprouting angiogenesis	TAS Traceable Author Statement more info	PubMed
involved_in blood vessel maturation	TAS Traceable Author Statement more info	PubMed
involved_in blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to BMP stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to growth factor stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to transforming growth factor beta stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in dorsal aorta morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in dorsal/ventral pattern formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in endocardial cushion morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
NOT involved_in endocardial cushion to mesenchymal transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in endothelial tube morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	IBA Inferred from Biological aspect of Ancestor more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in lymphangiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in lymphatic endothelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of Notch signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of SMAD protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of bicellular tight junction assembly	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of chondrocyte differentiation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of epithelial cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA replication	TAS Traceable Author Statement more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of blood vessel endothelial cell migration	TAS Traceable Author Statement more info	PubMed
involved_in regulation of endothelial cell proliferation	TAS Traceable Author Statement more info	PubMed
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in retina vasculature development in camera-type eye	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in venous blood vessel development	ISS Inferred from Sequence or Structural Similarity more info
involved_in wound healing, spreading of epidermal cells	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of BMP receptor complex	IBA Inferred from Biological aspect of Ancestor more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: serine/threonine-protein kinase receptor R3

Names: TGF-B superfamily receptor type I; activin A receptor type II-like 1; activin A receptor type IL; activin A receptor, type II-like kinase 1

NP_000011.2

EC 2.7.11.30

NP_001070869.1

EC 2.7.11.30

NP_001393416.1

EC 2.7.11.30

NP_001393417.1

EC 2.7.11.30

NP_001393418.1

EC 2.7.11.30

NP_001393419.1

EC 2.7.11.30

NP_001393420.1

EC 2.7.11.30

NP_001393421.1

EC 2.7.11.30

NP_001393422.1

EC 2.7.11.30

NP_001393423.1

EC 2.7.11.30

NP_001393424.1

EC 2.7.11.30

XP_047285857.1

EC 2.7.11.30

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009549.1 RefSeqGene

Range

5001..20944

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_543

mRNA and Protein(s)

NM_000020.3 → NP_000011.2 serine/threonine-protein kinase receptor R3 isoform 1 precursor

See identical proteins and their annotated locations for NP_000011.2

Status: REVIEWED

Source sequence(s)

AC025259, DN999570, Z22533

Consensus CDS

CCDS31804.1

UniProtKB/Swiss-Prot

A6NGA8, P37023

UniProtKB/TrEMBL

A0A0S2Z310

Related

ENSP00000373574.4, ENST00000388922.9

Conserved Domains (2) summary

cd14142
Location:196 → 493

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam08515
Location:173 → 200

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001077401.2 → NP_001070869.1 serine/threonine-protein kinase receptor R3 isoform 1 precursor

See identical proteins and their annotated locations for NP_001070869.1

Status: REVIEWED

Source sequence(s)

AC025259, BC042637

Consensus CDS

CCDS31804.1

UniProtKB/Swiss-Prot

A6NGA8, P37023

UniProtKB/TrEMBL

A0A0S2Z310

Related

ENSP00000447884.1, ENST00000550683.5

Conserved Domains (2) summary

cd14142
Location:196 → 493

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam08515
Location:173 → 200

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001406487.1 → NP_001393416.1 serine/threonine-protein kinase receptor R3 isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AC025259

Consensus CDS

CCDS31804.1

UniProtKB/Swiss-Prot

A6NGA8, P37023

UniProtKB/TrEMBL

A0A0S2Z310

Related

ENSP00000455848.2, ENST00000551576.6
NM_001406488.1 → NP_001393417.1 serine/threonine-protein kinase receptor R3 isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC025259

UniProtKB/TrEMBL

H3BTZ2

Related

ENSP00000457394.2, ENST00000552678.2
NM_001406489.1 → NP_001393418.1 serine/threonine-protein kinase receptor R3 isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC025259

UniProtKB/TrEMBL

H3BTZ2
NM_001406490.1 → NP_001393419.1 serine/threonine-protein kinase receptor R3 isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AC025259
NM_001406491.1 → NP_001393420.1 serine/threonine-protein kinase receptor R3 isoform 4 precursor

Status: REVIEWED

Source sequence(s)

AC025259

UniProtKB/TrEMBL

A0A0S2Z2Y4
NM_001406492.1 → NP_001393421.1 serine/threonine-protein kinase receptor R3 isoform 4 precursor

Status: REVIEWED

Source sequence(s)

AC025259

UniProtKB/TrEMBL

A0A0S2Z2Y4

Related

ENSP00000446724.2, ENST00000547400.6
NM_001406493.1 → NP_001393422.1 serine/threonine-protein kinase receptor R3 isoform 5 precursor

Status: REVIEWED

Source sequence(s)

AC025259
NM_001406494.1 → NP_001393423.1 serine/threonine-protein kinase receptor R3 isoform 6 precursor

Status: REVIEWED

Source sequence(s)

AC025259
NM_001406495.1 → NP_001393424.1 serine/threonine-protein kinase receptor R3 isoform 7 precursor

Status: REVIEWED

Source sequence(s)

AC025259

Related

ENSP00000392492.2, ENST00000419526.6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

51906944..51923361

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047429901.1 → XP_047285857.1 serine/threonine-protein kinase receptor R3 isoform X1

UniProtKB/Swiss-Prot

A6NGA8, P37023

UniProtKB/TrEMBL

A0A0S2Z310