Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

ACVR1

contributors: shn/npt/pgu - updated : 03-04-2018

HGNC name	activin A receptor, type I
HGNC id	171

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001105 11 - 3062 NP_001096 65 509 mouse lens epithelium 2009 19733164 NM_001111067 11 - 2881 NP_001104537 65 509 - 2009 19733164 NM_001347665 12 - 2951 NP_001334594 65 509 - 2009 19733164 NM_001347666 12 - 3011 NP_001334595 65 509 - 2009 19733164 NM_001347663 8 - 2918 NP_001334592 65 509 - 2009 19733164 NM_001347664 8 - 2983 NP_001334593 65 509 - 2009 19733164 NM_001347667 12 - 2954 NP_001334596 65 509 - 2009 19733164

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Nervous brain       highly Respiratory lung       highly Skeleton appendicular skeleton         Homo sapiens Urinary kidney       highly Visual eye lens     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly Homo sapiens Muscular       highly

cells

System Cell Pubmed Species Stage Rna symbol not specific chondrocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a small cysteine-rich extracellular region
	a juxtamembrane region of phosphorylation, glycine and serine rich (GS)
	a cytoplasmic serine/threonine kinase domain

HOMOLOGY

interspecies

ortholog to murine Acvr1

intraspecies

homolog to ALK3, ALK4

Homologene

FAMILY	type I bone morphogenetic protein (BMP) receptor family
	TKL Ser/Thr protein kinase family
	TGFB receptor subfamily

CATEGORY

enzyme , receptor

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	functioning as a BMP type I receptor and inducing Indian hedgehog in chondrocytes during skeletal development
	Acvr1 is involved in the proper specification of the left-right axis in mice and in promoting cell proliferation in the neural crest-derived cells of Meckel cartilage
	Acvr1 plays a role in mouse lens development by regulating lens cell proliferation
	transmembrane serine/threonine kinase receptor that activates intracellular signaling pathways via Smad1/5, Erk1/2, and MAPK14 in response to BMP binding
	BMPR1A and ACVR1, activate multiple signaling pathways to regulate lens formation
	induction of the osteoblastic differentiation of myoblasts by ALK2 seems to be dependent on its kinase activity, which phosphorylates Smad1/5 at its C- termini
	can repress osteogenesis and Wnt signaling via SOST/DKK1
	signaling via ACVR1 is required for appropriate aortic valve development in utero, and defects in this process lead to indirect secondary complications later in life
	is required for chondrocyte proliferation and differentiation, particularly in craniofacial and axial elements, but exerts coordinated functions with both BMPR1A and BMPR1B throughout the developing endochondral skeleton
	exerts key and non-redundant roles in numerous developmental processes, including the specification, growth and morphogenesis of endochondral skeletal elements
	plays an important role in bone development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

forming a stable complex with type II receptor after ligand binding

INTERACTION

DNA

RNA

small molecule

protein	not binding activin
	inhibiting TGFB1, TGFB2, BMP2
	cell quiescence controlled by BMP signaling via ACVR1 is required for transient formation of nodal cilia
	key receptor of BMP7
	BMP7 signaling through ACVR1 can reduce Wnt signaling via SOST/DKK1 and then inhibits osteogenesis
	GIPC1, ACVR1, BMPR1A, and TGFBR1 are signaling components required for TGFBR3-mediated endothelial cell epithelial-mesenchymal transformation
	bone morphogenetic protein signaling mediated by ACVR1 and DLX2 regulates apoptosis in glioma-initiating cells
	GDF2 and BMP10 enhance TNF-induced monocyte recruitment to the vascular endothelium mainly via ACVR1
	FKBP1A preferentially targets the BMP receptor ACVR1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

FOP

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     epiblast-specific deletion of ACVR1 compromised potentially development of nodal cilia, which results in defects in leftward fluid flow and, thus, abnormalities in left-right patterning constitutional     --low   loss of ACVR1 in osteoblasts increases bone density tumoral germinal mutation     gain of function in Diffuse Intrinsic Pontine Gliomas (DIPGs)

Susceptibility

to orofacial cleft

Variant & Polymorphism other	variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed osteoarticular bone   small molecule inhibition of BMP type I receptor activity may be useful in treating FOP and heterotopic ossification syndromes associated with excessive BMP signaling osteoarticular bone   as a plausible therapeutic target during early chondrogenic stages of lesion formation for preventing heterotopic bone formation in FOP and other conditions

ANIMAL & CELL MODELS

	Postnatal overexpression of constitutively active Q207D-mutant Alk2 in the left hindlimbs of mice led development of ectopic endochondral bone formation, joint fusion, and functional impairment, thus phenocopying key aspects of human FOP .
	Acvr1 conditional mouse knockout leads to an increase in apoptosis of lens epithelial and fiber cells resulting in smaller sizes of Acvr1 CKO mouse lenses
	Acvr1 deficiency in mouse embryonic fibroblasts (MEFs) resulted in severe defects in their quiescence-induced primary cilia
	bone mass was increased in the Acvr1-null mice
	Acvr1(CKO) mice are viable but exhibit defects in the development of cranial and axial structures