GeneBe

ACVR1B

protein-coding

activin A receptor type 1B, the group of Type 1 receptor serine/threonine kinases

Gene summary

This gene encodes an activin A type IB receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

Previous symbols:
  • ACVRLK4

MANE transcript

NM_004302.5

Inheritance

—

ClinVar variants

P:3U:37B:1

Top phenotype

Carcinoma of pancreas

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr12:51,951,699-51,997,078

External References & Databases

Ensembl (ENSG00000135503)NCBI Gene (91)OMIM (601300)HGNC:172GenCCUniProt (P36896)AlphaFoldClinVar (ACVR1B)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~45.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

malignant pancreatic neoplasmNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0009831

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACVR1B variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 37
Carcinoma of pancreasTotal: 3
not providedTotal: 2
Dextro-looped transposition of the great arteriesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004302.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
 2
missense
1
clinvar
34
clinvar
 35
nonsense
0
start loss
0
frameshift
1
clinvar
1
clinvar
 2
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total30370141
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004302.5RefSeqNP_004293.19MANE Select
ENST00000257963.9EnsemblENSP00000257963.49MANE Select
NM_001412774.1RefSeqNP_001399703.110Standard
NM_001412775.1RefSeqNP_001399704.19Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
acvr1baDanio rerio

Structure: fin regeneration

Quality: disrupted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • TGF-beta signaling pathway - Homo sapiens (human)
  • Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
  • Cytokine-cytokine receptor interaction - Homo sapiens (human)
  • TGF-Core
  • miR-targeted genes in muscle cell - TarBase

Biological Process

  • G1/S transition of mitotic cell cycle
  • in utero embryonic development
  • hair follicle development
  • regulation of transcription, DNA-templated
  • protein phosphorylation

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

Cellular Component

  • cytosol
  • plasma membrane
  • integral component of plasma membrane
  • cell surface
  • receptor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000541224
Coding exons
10
Length
45412
Individuals with no LoFs
125745
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125747
p
0.00000795
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.371483170.4670.00001893540
Missense (PolyPhen)58168.750.343711743
Synonymous0.5541131210.9360.000007131084
Loss of Function4.69127.50.03630.00000164300

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000880.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine- threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C- terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, ECO:0000269|PubMed:9892009}.;
Disease
DISEASE: Note=ACVRIB is abundantly expressed in systemic sclerosis patient fibroblasts and production of collagen is also induced by activin-A/INHBA. This suggests that the activin/ACRV1B signaling mechanism is involved in systemic sclerosis. {ECO:0000269|PubMed:21377836}.;

Recessive Scores

pRec
0.297

Intolerance Scores

LoFtool
0.0435
RVIS EVS
-0.41
RVIS percentile EVS
26.23

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.997

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.