SMAD6 SMAD family member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMAD6provided by HGNC
Official Full Name: SMAD family member 6provided by HGNC
Primary source: HGNC:HGNC:6772
See related: Ensembl:ENSG00000137834 MIM:602931; AllianceGenome:HGNC:6772
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: AOVD2; MADH6; MADH7; HsT17432
Summary: The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]
Expression: Broad expression in lung (RPKM 6.3), placenta (RPKM 2.8) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q22.31

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (66702236..66782849)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (64524017..64604653)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (66994574..67075187)

Chromosome 15 - NC_000015.10 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 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?

Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway.
Title: Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway.
Homozygous SMAD6 variants in two unrelated patients with craniosynostosis and radioulnar synostosis.
Title: Homozygous SMAD6 variants in two unrelated patients with craniosynostosis and radioulnar synostosis.
Down-regulation of hsa-circ-0107593 promotes osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.
Title: Down-regulation of hsa-circ-0107593 promotes osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.
miR-20a-5p regulated SMAD6 to inhibit chondrogenesis of hDPSCs.
Title: miR-20a-5p regulated SMAD6 to inhibit chondrogenesis of hDPSCs.
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.
Assessing the prevalence of S-shaped root canal and associated genes in humans.
Title: Assessing the prevalence of S-shaped root canal and associated genes in humans.
A genotype and phenotype analysis of SMAD6 mutant patients with radioulnar synostosis.
Title: A genotype and phenotype analysis of SMAD6 mutant patients with radioulnar synostosis.
SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis.
Title: SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis.
Genetic variants in bone morphogenetic proteins signaling pathway might be involved in palatal rugae phenotype in humans.
Title: Genetic variants in bone morphogenetic proteins signaling pathway might be involved in palatal rugae phenotype in humans.
Arginine methylation of R81 in Smad6 confines BMP-induced Smad1 signaling.
Title: Arginine methylation of R81 in Smad6 confines BMP-induced Smad1 signaling.

Submit: New GeneRIF Correction See all GeneRIFs (63)

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
Aortic valve disease 2 MedGen: C3542024 OMIM: 614823 GeneReviews: Not available	Compare labs
Craniosynostosis 7 MedGen: C4479496 OMIM: 617439 GeneReviews: Not available	Compare labs
Radioulnar synostosis, nonsyndromic, susceptibility to MedGen: C5241445 OMIM: 179300 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide gene-environment interaction analysis for tobacco smoke and lung cancer susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of SMAD family member 6 (SMAD6) in human B cells	PubMed
Tat	tat	SMAD6 expression and its phosphorylation, in response to bone morphogenetic protein-2 (BMP2) treatment, is downregulated by HIV-1 Tat treatment in the macrophage cell line U937	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D15S1301 (e-PCR)
- UniSTS:1289

CHLC.GGAA28H03 (e-PCR)
- UniSTS:6439

SHGC-146780 (e-PCR)
- UniSTS:175425

SHGC-147716 (e-PCR)
- UniSTS:175967

RH47721 (e-PCR)
- UniSTS:67468

Smad5 (e-PCR), detects polymorphism
- UniSTS:466573

RH15748 (e-PCR)
- UniSTS:14989

AB071130 (e-PCR)
- UniSTS:479958

RH70683 (e-PCR)
- UniSTS:1256

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables I-SMAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables I-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables R-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables co-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction 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 sequestering activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription regulator inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transcription regulator inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription regulator inhibitor activity	TAS Traceable Author Statement more info	PubMed
enables type I activin receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables type I transforming growth factor beta receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction 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 SMAD protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in anatomical structure morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in aorta development	IEA Inferred from Electronic Annotation more info
involved_in aortic valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-substrate adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in coronary vasculature development	IEA Inferred from Electronic Annotation more info
involved_in fat cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitral valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of SMAD protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of activin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	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 ossification	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in outflow tract septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of miRNA transcription	IEA Inferred from Electronic Annotation more info
involved_in pulmonary valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to estrogen	IEA Inferred from Electronic Annotation more info
involved_in response to laminar fluid shear stress	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in ureteric bud development	IEA Inferred from Electronic Annotation more info
involved_in ventricular septum development	IEA Inferred from Electronic Annotation more info
involved_in zygotic specification of dorsal/ventral axis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in chromatin	ISA Inferred from Sequence Alignment more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
part_of heteromeric SMAD protein complex	IBA Inferred from Biological aspect of Ancestor more info
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mothers against decapentaplegic homolog 6

Names: MAD homolog 6; SMAD, mothers against DPP homolog 6; mothers against decapentaplegic, drosophila, homolog of, 6

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_012244.2 RefSeqGene

Range

4901..85514

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005585.5 → NP_005576.3 mothers against decapentaplegic homolog 6

See identical proteins and their annotated locations for NP_005576.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the supported protein.

Source sequence(s)

AC013564, AC110048, AF035528, BC012986, BC029288, CA406301, CN314453, CN314455, U59914

Consensus CDS

CCDS10221.1

UniProtKB/Swiss-Prot

A9J6M5, O43541, O43654, Q15799, Q7Z7L4, Q96E31, Q9UKZ3

Related

ENSP00000288840.5, ENST00000288840.10

Conserved Domains (2) summary

cd10493
Location:160 → 273

MH1_SMAD_6; N-terminal Mad Homology 1 (MH1) domain in SMAD6

cd10499
Location:322 → 494

MH2_SMAD_6; C-terminal Mad Homology 2 (MH2) domain in SMAD6

RNA

NR_027654.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as SMAD6B, includes an alternate exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC013564, AC110048, AF035528, AM909653, BC029288, CA406301, CN314453, CN314455, U59914

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

66702236..66782849

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011521561.3 → XP_011519863.1 mothers against decapentaplegic homolog 6 isoform X1

See identical proteins and their annotated locations for XP_011519863.1

UniProtKB/Swiss-Prot

O43541

Conserved Domains (1) summary

cd10499
Location:61 → 233

MH2_SMAD_6; C-terminal Mad Homology 2 (MH2) domain in SMAD6

RNA

XR_931827.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

64524017..64604653

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054377916.1 → XP_054233891.1 mothers against decapentaplegic homolog 6 isoform X1

RNA

XR_008488949.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001142861.2: Suppressed sequence

Description

NM_001142861.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which appears to be incomplete at the 5' end.