Aliases for SMCR8 Gene

Aliases for SMCR8 Gene

  • SMCR8-C9orf72 Complex Subunit 2 3 5
  • Smith-Magenis Syndrome Chromosomal Region Candidate Gene 8 Protein 3 4
  • Smith-Magenis Syndrome Chromosome Region, Candidate 8 2 3
  • Guanine Nucleotide Exchange Protein SMCR8 3 4
  • DENND8A 2 3
  • FLJ34716 2
  • SMCR8 5

External Ids for SMCR8 Gene

Previous GeneCards Identifiers for SMCR8 Gene

  • GC17P018463
  • GC17P019590
  • GC17P018161
  • GC17P018420
  • GC17P018421
  • GC17P018159
  • GC17P018218
  • GC17P017972
  • GC17P018317
  • GC17P018359
  • GC17P018605
  • GC17P018622
  • GC17P018641
  • GC17P018720
  • GC17P018409
  • GC17P018445
  • GC17P018453
  • GC17P018473
  • GC17P018493
  • GC17P018524
  • GC17P018557
  • GC17P018574
  • GC17P018807

Summaries for SMCR8 Gene

GeneCards Summary for SMCR8 Gene

SMCR8 (SMCR8-C9orf72 Complex Subunit) is a Protein Coding gene. Diseases associated with SMCR8 include Smith-Magenis Syndrome and Dermatopathia Pigmentosa Reticularis. Among its related pathways are Pathways of neurodegeneration - multiple diseases and Autophagy - animal.

UniProtKB/Swiss-Prot Summary for SMCR8 Gene

  • Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531).

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SMCR8 Gene

Genomics for SMCR8 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SMCR8 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMCR8 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SMCR8

Top Transcription factor binding sites by QIAGEN in the SMCR8 gene promoter:
  • AREB6
  • Elk-1
  • Nkx2-5
  • Pax-2
  • Pax-2a
  • Pax-2b
  • STAT1
  • STAT1alpha
  • STAT1beta
  • YY1

Genomic Locations for SMCR8 Gene

Latest Assembly
chr17:18,315,293-18,328,056
(GRCh38/hg38)
Size:
12,764 bases
Orientation:
Plus strand

Previous Assembly
chr17:18,218,607-18,231,370
(GRCh37/hg19 by Entrez Gene)
Size:
12,764 bases
Orientation:
Plus strand

chr17:18,218,624-18,226,517
(GRCh37/hg19 by Ensembl)
Size:
7,894 bases
Orientation:
Plus strand

Genomic View for SMCR8 Gene

Genes around SMCR8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMCR8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMCR8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMCR8 Gene

Proteins for SMCR8 Gene

  • Protein details for SMCR8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TEV9-SMCR8_HUMAN
    Recommended name:
    Guanine nucleotide exchange protein SMCR8
    Protein Accession:
    Q8TEV9
    Secondary Accessions:
    • A5PKZ5
    • Q3ZCN0
    • Q6PJL3

    Protein attributes for SMCR8 Gene

    Size:
    937 amino acids
    Molecular mass:
    105022 Da
    Quaternary structure:
    • Interacts with C9orf72; the interaction is direct (PubMed:27559131, PubMed:27617292). Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex associates with the ATG1/ULK1 kinase complex (PubMed:28195531).

    Three dimensional structures from OCA and Proteopedia for SMCR8 Gene

    Alternative splice isoforms for SMCR8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMCR8 Gene

Post-translational modifications for SMCR8 Gene

  • Phosphorylation by TBK1 is required to promote autophagosome maturation (PubMed:27103069). Phosphorylated by ULK1 (PubMed:27103069).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SMCR8 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SMCR8 Gene

Domains & Families for SMCR8 Gene

Gene Families for SMCR8 Gene

Protein Domains for SMCR8 Gene

Suggested Antigen Peptide Sequences for SMCR8 Gene

GenScript: Design optimal peptide antigens:
  • Smith-Magenis syndrome chromosomal region candidate gene 8 protein (SMCR8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TEV9

UniProtKB/Swiss-Prot:

SMCR8_HUMAN :
  • Belongs to the SMCR8 family.
Family:
  • Belongs to the SMCR8 family.
genes like me logo Genes that share domains with SMCR8: view

Function for SMCR8 Gene

Molecular function for SMCR8 Gene

UniProtKB/Swiss-Prot Function:
Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531).

Phenotypes From GWAS Catalog for SMCR8 Gene

Gene Ontology (GO) - Molecular Function for SMCR8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004860 protein kinase inhibitor activity IMP 28195531
GO:0005085 contributes_to guanyl-nucleotide exchange factor activity IBA,IDA 27103069
GO:0005515 protein binding IPI 27103069
GO:0019901 protein kinase binding IPI 27103069
genes like me logo Genes that share ontologies with SMCR8: view
genes like me logo Genes that share phenotypes with SMCR8: view

Animal Models for SMCR8 Gene

MGI Knock Outs for SMCR8:
  • Smcr8 Smcr8<tm1.1(KOMP)Vlcg>
  • Smcr8 Smcr8<tm1(KOMP)Vlcg>

miRNA for SMCR8 Gene

miRTarBase miRNAs that target SMCR8

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMCR8

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SMCR8 Gene

Localization for SMCR8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMCR8 Gene

Cytoplasm. Nucleus. Note=Localizes mainly in the cytoplasm. {ECO:0000269 PubMed:28195531}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMCR8 gene
Compartment Confidence
nucleus 5
endosome 2
cytosol 2
lysosome 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SMCR8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IDA 28195531
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA 28195531
GO:0005737 cytoplasm IEA,IDA 27193190
GO:0032045 guanyl-nucleotide exchange factor complex IBA,IDA 27103069
genes like me logo Genes that share ontologies with SMCR8: view

Pathways & Interactions for SMCR8 Gene

genes like me logo Genes that share pathways with SMCR8: view

Pathways by source for SMCR8 Gene

SIGNOR curated interactions for SMCR8 Gene

Activates:
Inactivates:

Gene Ontology (GO) - Biological Process for SMCR8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006469 negative regulation of protein kinase activity IMP 28195531
GO:0006914 autophagy IEA --
GO:0010506 regulation of autophagy IEA,IMP 27103069
GO:0010629 negative regulation of gene expression IMP 28195531
GO:0016242 negative regulation of macroautophagy IMP 28195531
genes like me logo Genes that share ontologies with SMCR8: view

Drugs & Compounds for SMCR8 Gene

No Compound Related Data Available

Transcripts for SMCR8 Gene

mRNA/cDNA for SMCR8 Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMCR8

Alternative Splicing Database (ASD) splice patterns (SP) for SMCR8 Gene

No ASD Table

Relevant External Links for SMCR8 Gene

GeneLoc Exon Structure for
SMCR8

Expression for SMCR8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SMCR8 Gene

Protein differential expression in normal tissues from HIPED for SMCR8 Gene

This gene is overexpressed in Monocytes (23.7), Ovary (16.8), Frontal cortex (10.6), and Testis (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SMCR8 Gene



Protein tissue co-expression partners for SMCR8 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SMCR8

SOURCE GeneReport for Unigene cluster for SMCR8 Gene:

Hs.592944

mRNA Expression by UniProt/SwissProt for SMCR8 Gene:

Q8TEV9-SMCR8_HUMAN
Tissue specificity: Expressed in all tissues tested.

Evidence on tissue expression from TISSUES for SMCR8 Gene

  • Eye(4.2)
  • Nervous system(3.7)
  • Intestine(2.8)
  • Lung(2.7)
  • Skin(2.4)
  • Kidney(2.3)
  • Thyroid gland(2.1)
genes like me logo Genes that share expression patterns with SMCR8: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SMCR8 Gene

Orthologs for SMCR8 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SMCR8 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SMCR8 30 31
  • 99.72 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SMCR8 30 31
  • 88.76 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Smcr8 30
  • 86.1 (n)
Mouse
(Mus musculus)
Mammalia Smcr8 30 17 31
  • 86.06 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SMCR8 31
  • 82 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia SMCR8 30 31
  • 81.79 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SMCR8 31
  • 76 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SMCR8 30 31
  • 71.9 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SMCR8 31
  • 70 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia smcr8 30
  • 63.42 (n)
Zebrafish
(Danio rerio)
Actinopterygii smcr8a 30 31
  • 60.21 (n)
OneToMany
smcr8b 31
  • 40 (a)
OneToMany
Species where no ortholog for SMCR8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for SMCR8 Gene

ENSEMBL:
Gene Tree for SMCR8 (if available)
TreeFam:
Gene Tree for SMCR8 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMCR8: view image

Paralogs for SMCR8 Gene

No data available for Paralogs for SMCR8 Gene

Variants for SMCR8 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SMCR8 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
982661 Uncertain Significance: Neurodevelopmental disorder 18,322,660(+) C/T
NM_144775.3(SMCR8):c.2404C>T (p.Arg802Cys)
MISSENSE
rs79875842 Benign: not provided 18,316,954(+) A/G
NM_144775.3(SMCR8):c.1165A>G (p.Ile389Val)
MISSENSE
rs12449313 - p.Asn636Ser
rs1563632 - p.Arg556His
rs8080966 - p.Pro524Leu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SMCR8 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for SMCR8 Gene

Variant ID Type Subtype PubMed ID
esv1004827 CNV deletion 20482838
nsv155 OTHER inversion 15895083
nsv428333 CNV gain 18775914
nsv473957 CNV novel sequence insertion 20440878
nsv499114 OTHER inversion 21111241
nsv521075 CNV loss 19592680
nsv833386 CNV gain 17160897
nsv833387 CNV loss 17160897

Variation tolerance for SMCR8 Gene

Residual Variation Intolerance Score: 36.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.54; 85.99% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMCR8 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMCR8

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMCR8 Gene

Disorders for SMCR8 Gene

MalaCards: The human disease database

(7) MalaCards diseases for SMCR8 Gene - From: COP and GCD

Additional Disease Information for SMCR8

genes like me logo Genes that share disorders with SMCR8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SMCR8 Gene

Publications for SMCR8 Gene

  1. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. (PMID: 27103069) Sellier C … Charlet-Berguerand N (The EMBO journal 2016) 2 3 4
  2. Discovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease. (PMID: 23248642) Zhang D … Aravind L (Frontiers in genetics 2012) 2 3 4
  3. Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. (PMID: 11997338) Bi W … Lupski JR (Genome research 2002) 2 3 4
  4. Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. (PMID: 28195531) Jung J … Behrends C (eLife 2017) 3 4
  5. C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. (PMID: 27559131) Amick J … Ferguson SM (Molecular biology of the cell 2016) 3 4

Products for SMCR8 Gene

Sources for SMCR8 Gene