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Smo smoothened, frizzled class receptor [ Mus musculus (house mouse) ]

Gene ID: 319757, updated on 11-Jun-2025

Summary

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Official Symbol: Smoprovided by MGI
Official Full Name: smoothened, frizzled class receptorprovided by MGI
Primary source: MGI:MGI:108075
See related: Ensembl:ENSMUSG00000001761 AllianceGenome:MGI:108075
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: bnb; Smoh; smoothened; E130215L21Rik
Summary: Enables oxysterol binding activity; protein kinase A catalytic subunit binding activity; and protein sequestering activity. Involved in several processes, including regionalization; regulation of animal organ morphogenesis; and regulation of macromolecule metabolic process. Acts upstream of or within several processes, including nervous system development; positive regulation of cell population proliferation; and regionalization. Located in several cellular components, including centriole; ciliary membrane; and endoplasmic reticulum-Golgi intermediate compartment. Is active in Golgi apparatus. Is expressed in several structures, including 1st branchial arch; alimentary system; central nervous system; genitourinary system; and skeleton. Used to study medulloblastoma and pulmonary emphysema. Human ortholog(s) of this gene implicated in basal cell carcinoma; hepatocellular carcinoma; malignant pleural mesothelioma; pancreatic cancer; and pancreatic ductal carcinoma. Orthologous to human SMO (smoothened, frizzled class receptor). [provided by Alliance of Genome Resources, Jun 2025]
Expression: Broad expression in ovary adult (RPKM 53.2), limb E14.5 (RPKM 37.8) and 25 other tissues See more
Orthologs: human all
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Genomic context

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See Smo in Genome Data Viewer

Location:: 6 A3.3; 6 12.36 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	6	NC_000072.7 (29735480..29761359)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	6	NC_000072.6 (29735497..29761366)

Chromosome 6 - NC_000072.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hedgehog signal activates AMPK via Smoothened to promote autophagy and lipid degradation in hepatocytes.
Title: Hedgehog signal activates AMPK via Smoothened to promote autophagy and lipid degradation in hepatocytes.
STAT3 is required for Smo-dependent signaling and mediates Smo-targeted treatment resistance and tumorigenesis in Shh medulloblastoma.
Title: STAT3 is required for Smo-dependent signaling and mediates Smo-targeted treatment resistance and tumorigenesis in Shh medulloblastoma.
TMED2 binding restricts SMO to the ER and Golgi compartments.
Title: TMED2 binding restricts SMO to the ER and Golgi compartments.
Smoothened and ARL13B are critical in mouse for superior cerebellar peduncle targeting.
Title: Smoothened and ARL13B are critical in mouse for superior cerebellar peduncle targeting.
Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength.
Title: Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength.
E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened.
Title: E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened.
Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.
Title: Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.
Ubiquitin links smoothened to intraflagellar transport to regulate Hedgehog signaling.
Title: Ubiquitin links smoothened to intraflagellar transport to regulate Hedgehog signaling.
SMO-M2 mutation does not support cell-autonomous Hedgehog activity in cerebellar granule cell precursors.
Title: SMO-M2 mutation does not support cell-autonomous Hedgehog activity in cerebellar granule cell precursors.
Smo deletion mediates articular cartilage degeneration by ADAMTS-5 and Runx2 suppression
Title: Attenuation of Post-Traumatic Osteoarthritis After Anterior Cruciate Ligament Injury Via Inhibition of Hedgehog Signaling.

Submit: New GeneRIF Correction See all GeneRIFs (98)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (6) 1 citation
Endonuclease-mediated (3)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:237068

Smoh (e-PCR), detects polymorphism
- UniSTS:144443

AU041277 (e-PCR)
- UniSTS:160324

Smo (e-PCR), detects polymorphism
- UniSTS:465497

D6Mit159 (e-PCR), detects polymorphism
- UniSTS:116597

NoName (e-PCR)
- UniSTS:548507

Smo (e-PCR), detects polymorphism
- UniSTS:546036

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	IEA Inferred from Electronic Annotation more info
enables cAMP-dependent protein kinase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables cAMP-dependent protein kinase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables oxysterol binding	IDA Inferred from Direct Assay more info	PubMed
enables patched binding	IBA Inferred from Biological aspect of Ancestor more info
enables patched binding	IEA Inferred from Electronic Annotation more info
enables patched binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase A catalytic subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein sequestering activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in alpha-tubulin acetylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within anterior/posterior pattern specification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within astrocyte activation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within atrial septum morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in axon extension involved in axon guidance	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell fate specification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cholesterol	IEP Inferred from Expression Pattern more info	PubMed
involved_in central nervous system development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within central nervous system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within central nervous system neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cerebellar cortex morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cerebral cortex development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in commissural neuron axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in commissural neuron axon guidance	ISO Inferred from Sequence Orthology more info
involved_in contact inhibition	IEA Inferred from Electronic Annotation more info
involved_in contact inhibition	ISO Inferred from Sequence Orthology more info
involved_in contact inhibition	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within dentate gyrus development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of left/right asymmetry in lateral mesoderm	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within determination of left/right symmetry	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in developmental growth	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within developmental growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within digestive tract development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dopaminergic neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dorsal/ventral neural tube patterning	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dorsal/ventral pattern formation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within embryonic organ development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within epithelial-mesenchymal cell signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in forebrain morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within gene expression	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of hair follicle development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hair follicle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart looping	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heart morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within homeostasis of number of cells within a tissue	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within in utero embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within left/right axis specification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mammary gland epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesenchymal to epithelial transition	IEA Inferred from Electronic Annotation more info
involved_in mesenchymal to epithelial transition	ISO Inferred from Sequence Orthology more info
involved_in mesenchymal to epithelial transition involved in metanephric renal vesicle formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in midgut development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism growth	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within myoblast migration	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of DNA binding	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of hair follicle development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hepatocyte proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neural crest cell migration	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of neuroblast proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within odontogenesis of dentin-containing tooth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ossification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in osteoblast differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pancreas morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pattern specification process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within pattern specification process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of branching involved in ureteric bud morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of hepatic stellate cell activation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of mesenchymal cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neural precursor cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neural precursor cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of neuroblast proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of organ growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of protein import into nucleus	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vascular associated smooth muscle cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of protein import into nucleus	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein stabilization	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of cerebellar granule cell precursor proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of localization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of somatic stem cell population maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to inositol	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within skeletal muscle fiber development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smooth muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within smoothened signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smoothened signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in somite development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within spinal cord dorsal/ventral patterning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spinal cord dorsal/ventral patterning	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within thalamus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within type B pancreatic cell development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within vasculogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ventral midline determination	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in 9+0 non-motile cilium	IDA Inferred from Direct Assay more info	PubMed
is_active_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with Golgi apparatus	IEA Inferred from Electronic Annotation more info
colocalizes_with Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in axonal growth cone	ISO Inferred from Sequence Orthology more info
colocalizes_with caveola	IEA Inferred from Electronic Annotation more info
colocalizes_with caveola	ISO Inferred from Sequence Orthology more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in centriole	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary membrane	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary membrane	TAS Traceable Author Statement more info
is_active_in cilium	IBA Inferred from Biological aspect of Ancestor more info
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	IEA Inferred from Electronic Annotation more info
is_active_in cilium	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cilium	ISO Inferred from Sequence Orthology more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendritic growth cone	ISO Inferred from Sequence Orthology more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IEA Inferred from Electronic Annotation more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology 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	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane bounded cell projection	IEA Inferred from Electronic Annotation more info
is_active_in postsynapse	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: protein smoothened

Names: bent body; smoothened homolog

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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.

mRNA and Protein(s)

NM_176996.5 → NP_795970.3 protein smoothened precursor

See identical proteins and their annotated locations for NP_795970.3

Status: VALIDATED

Source sequence(s)

AC069469

Consensus CDS

CCDS19965.1

UniProtKB/Swiss-Prot

P56726

UniProtKB/TrEMBL

Q4VBD5

Related

ENSMUSP00000001812.5, ENSMUST00000001812.5

Conserved Domains (2) summary

cd07451
Location:70 → 200

CRD_SMO; Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein

pfam01534
Location:225 → 554

Frizzled; Frizzled/Smoothened family membrane region

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000072.7 Reference GRCm39 C57BL/6J

Range

29735480..29761359

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006505106.5 → XP_006505169.1 protein smoothened isoform X1

Conserved Domains (2) summary

cd15030
Location:90 → 420

7tmF_SMO_homolog; class F smoothened family membrane region, a homolog of frizzled receptors

cl02447
Location:1 → 66

CRD_FZ; CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain