This gene encodes a member of the Microrchidia (MORC) protein superfamily. The encoded protein is known to regulate the condensation of heterochromatin in response to DNA damage and play a role in repressing transcription. The protein has been found to regulate the activity of ATP citrate lyase via specific interaction with this enzyme in the cytosol of lipogenic breast cancer ... See more...

Aliases for MORC2 Gene

Aliases for MORC2 Gene

  • MORC Family CW-Type Zinc Finger 2 2 3 5
  • Zinc Finger CW-Type Coiled-Coil Domain Protein 1 3 4
  • ATPase MORC2 3 4
  • ZCWCC1 3 4
  • Zinc Finger, CW-Type With Coiled-Coil Domain 1 2
  • Zinc Finger, CW Type With Coiled-Coil Domain 1 2
  • MORC Family CW-Type Zinc Finger Protein 2 4
  • EC 3.6.1.3 4
  • KIAA0852 4
  • CMT2Z 3
  • ZCW3 3

External Ids for MORC2 Gene

Previous HGNC Symbols for MORC2 Gene

  • ZCWCC1

Previous GeneCards Identifiers for MORC2 Gene

  • GC22M029651
  • GC22M031322
  • GC22M014286

Summaries for MORC2 Gene

Entrez Gene Summary for MORC2 Gene

  • This gene encodes a member of the Microrchidia (MORC) protein superfamily. The encoded protein is known to regulate the condensation of heterochromatin in response to DNA damage and play a role in repressing transcription. The protein has been found to regulate the activity of ATP citrate lyase via specific interaction with this enzyme in the cytosol of lipogenic breast cancer cells. The protein also plays a role in lipogenesis and adipocyte differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

GeneCards Summary for MORC2 Gene

MORC2 (MORC Family CW-Type Zinc Finger 2) is a Protein Coding gene. Diseases associated with MORC2 include Charcot-Marie-Tooth Disease, Axonal, Type 2Z and Charcot-Marie-Tooth Disease. Gene Ontology (GO) annotations related to this gene include carbohydrate binding. An important paralog of this gene is MORC1.

UniProtKB/Swiss-Prot Summary for MORC2 Gene

  • Essential for epigenetic silencing by the HUSH (human silencing hub) complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing (PubMed:28581500, PubMed:29440755). Represses germ cell-related genes and L1 retrotransposons in collaboration with SETDB1 and the HUSH complex, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). During DNA damage response, regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, is phosphorylated by PAK1, both colocalize to chromatin and induce H2AFX expression. ATPase activity is required and dependent of phosphorylation by PAK1 and presence of DNA (PubMed:23260667). Recruits histone deacetylases, such as HDAC4, to promoter regions, causing local histone H3 deacetylation and transcriptional repression of genes such as CA9 (PubMed:20225202, PubMed:20110259). Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864).

Gene Wiki entry for MORC2 Gene

Additional gene information for MORC2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MORC2 Gene

Genomics for MORC2 Gene

GeneHancer (GH) Regulatory Elements for MORC2 Gene

Promoters and enhancers for MORC2 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 MORC2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MORC2

Top Transcription factor binding sites by QIAGEN in the MORC2 gene promoter:
  • CP2
  • NF-1
  • NF-1/L
  • NF-kappaB1
  • Nkx2-5
  • Pax-2
  • Pax-2a
  • RelA

Genomic Locations for MORC2 Gene

Genomic Locations for MORC2 Gene
chr22:30,925,130-30,968,774
(GRCh38/hg38)
Size:
43,645 bases
Orientation:
Minus strand
chr22:31,321,117-31,364,284
(GRCh37/hg19)
Size:
43,168 bases
Orientation:
Minus strand

Genomic View for MORC2 Gene

Genes around MORC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MORC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MORC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MORC2 Gene

Proteins for MORC2 Gene

  • Protein details for MORC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6X9-MORC2_HUMAN
    Recommended name:
    ATPase MORC2
    Protein Accession:
    Q9Y6X9
    Secondary Accessions:
    • B2RNB1
    • Q9UF28
    • Q9Y6V2

    Protein attributes for MORC2 Gene

    Size:
    1032 amino acids
    Molecular mass:
    117823 Da
    Quaternary structure:
    • Homodimerizes upon ATP-binding and dissociate upon ATP hydrolysis; homodimerization is required for gene silencing (PubMed:29440755). Interacts with HDAC4 (PubMed:20110259). Interacts with ACLY (PubMed:24286864). Interacts with TASOR and MPHOSPH8; the interactions associate MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci (PubMed:28581500).
    SequenceCaution:
    • Sequence=AAC12954.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAA74875.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MORC2 Gene

    Alternative splice isoforms for MORC2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MORC2 Gene

Post-translational modifications for MORC2 Gene

  • Phosphorylated by PAK1 at Ser-739 upon DNA damage. Phosphorylation is required for ATPase activity and recruitment to damaged chromatin.
  • Ubiquitination at Lys932
  • Modification sites at PhosphoSitePlus

Other Protein References for MORC2 Gene

No data available for DME Specific Peptides for MORC2 Gene

Domains & Families for MORC2 Gene

Gene Families for MORC2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for MORC2 Gene

Blocks:
  • CW-type Zn-finger
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MORC2 Gene

GenScript: Design optimal peptide antigens:
  • Zinc finger CW-type coiled-coil domain protein 1 (MORC2_HUMAN)
genes like me logo Genes that share domains with MORC2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for MORC2 Gene

Function for MORC2 Gene

Molecular function for MORC2 Gene

UniProtKB/Swiss-Prot Function:
Essential for epigenetic silencing by the HUSH (human silencing hub) complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing (PubMed:28581500, PubMed:29440755). Represses germ cell-related genes and L1 retrotransposons in collaboration with SETDB1 and the HUSH complex, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). During DNA damage response, regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, is phosphorylated by PAK1, both colocalize to chromatin and induce H2AFX expression. ATPase activity is required and dependent of phosphorylation by PAK1 and presence of DNA (PubMed:23260667). Recruits histone deacetylases, such as HDAC4, to promoter regions, causing local histone H3 deacetylation and transcriptional repression of genes such as CA9 (PubMed:20225202, PubMed:20110259). Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.1.3; Evidence={ECO:0000269 PubMed:23260667, ECO:0000269 PubMed:28581500, ECO:0000269 PubMed:29440755}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; Evidence=. ;.
UniProtKB/Swiss-Prot EnzymeRegulation:
ATPase activity is dependent of phosphorylation by PAK1 and presence of DNA.

Enzyme Numbers (IUBMB) for MORC2 Gene

Phenotypes From GWAS Catalog for MORC2 Gene

Gene Ontology (GO) - Molecular Function for MORC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 29440755
GO:0003682 chromatin binding IDA 23260667
GO:0005515 protein binding IPI 28581500
GO:0005524 ATP binding IDA,IEA 29440755
GO:0008270 zinc ion binding IDA 29440755
genes like me logo Genes that share ontologies with MORC2: view
genes like me logo Genes that share phenotypes with MORC2: view

Human Phenotype Ontology for MORC2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MORC2 Gene

MGI Knock Outs for MORC2:
  • Morc2a Morc2a<tm1b(KOMP)Wtsi>

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for MORC2

No data available for Transcription Factor Targets and HOMER Transcription for MORC2 Gene

Localization for MORC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MORC2 Gene

Nucleus. Cytoplasm, cytosol. Chromosome. Nucleus matrix. Note=Mainly located in the nucleus (PubMed:20225202). Upon phosphorylation at Ser-739, recruited to damaged chromatin (PubMed:23260667). {ECO:0000269 PubMed:20225202, ECO:0000269 PubMed:23260667}.

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 MORC2 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 1
cytoskeleton 1
mitochondrion 1
peroxisome 0
endoplasmic reticulum 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MORC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000792 heterochromatin IDA 28581500
GO:0005634 nucleus IBA,IDA 23260667
GO:0005654 nucleoplasm IDA --
GO:0005694 chromosome IEA --
GO:0005737 cytoplasm IEA,IDA 23260667
genes like me logo Genes that share ontologies with MORC2: view

Pathways & Interactions for MORC2 Gene

PathCards logo

SuperPathways for MORC2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for MORC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006338 chromatin remodeling IDA 23260667
GO:0006629 lipid metabolic process IEA --
GO:0006631 fatty acid metabolic process IEA --
GO:0006974 cellular response to DNA damage stimulus IDA 23260667
GO:0045814 negative regulation of gene expression, epigenetic IDA 28581500
genes like me logo Genes that share ontologies with MORC2: view

No data available for Pathways by source and SIGNOR curated interactions for MORC2 Gene

Drugs & Compounds for MORC2 Gene

No Compound Related Data Available

Transcripts for MORC2 Gene

mRNA/cDNA for MORC2 Gene

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

CRISPR Products

Clone Products

  • Addgene plasmids for MORC2

Alternative Splicing Database (ASD) splice patterns (SP) for MORC2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1:
SP2: - -
SP3:

ExUns: 24 ^ 25 ^ 26a · 26b ^ 27a · 27b
SP1:
SP2:
SP3: -

Relevant External Links for MORC2 Gene

GeneLoc Exon Structure for
MORC2

Expression for MORC2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MORC2 Gene

Protein differential expression in normal tissues from HIPED for MORC2 Gene

This gene is overexpressed in Kidney (21.0), Liver (13.3), and Adrenal (8.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MORC2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MORC2

SOURCE GeneReport for Unigene cluster for MORC2 Gene:

Hs.555918

mRNA Expression by UniProt/SwissProt for MORC2 Gene:

Q9Y6X9-MORC2_HUMAN
Tissue specificity: Highly expressed in smooth muscle, pancreas and testis.

Evidence on tissue expression from TISSUES for MORC2 Gene

  • Nervous system(4.3)
  • Liver(4.1)
genes like me logo Genes that share expression patterns with MORC2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MORC2 Gene

Orthologs for MORC2 Gene

This gene was present in the common ancestor of animals.

Orthologs for MORC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MORC2 31 30
  • 99.51 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MORC2 31 30
  • 90.96 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MORC2 31 30
  • 89.31 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Morc2 30
  • 86.76 (n)
mouse
(Mus musculus)
Mammalia Morc2a 17 31 30
  • 86.64 (n)
Morc2b 31
  • 69 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia MORC2 31
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MORC2 31
  • 62 (a)
OneToOne
chicken
(Gallus gallus)
Aves MORC2 31 30
  • 74.28 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 72 (a)
OneToMany
-- 31
  • 71 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia morc2 30
  • 66.55 (n)
Str.10569 30
zebrafish
(Danio rerio)
Actinopterygii morc2 31 30
  • 63.48 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea morc-1 31
  • 20 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 59 (a)
OneToOne
Species where no ortholog for MORC2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 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)

Evolution for MORC2 Gene

ENSEMBL:
Gene Tree for MORC2 (if available)
TreeFam:
Gene Tree for MORC2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MORC2: view image

Paralogs for MORC2 Gene

Paralogs for MORC2 Gene

(1) SIMAP similar genes for MORC2 Gene using alignment to 3 proteins:

  • MORC2_HUMAN
  • H7C1V1_HUMAN
  • H7C3M1_HUMAN
genes like me logo Genes that share paralogs with MORC2: view

Variants for MORC2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MORC2 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
639064 Uncertain Significance: Charcot-Marie-Tooth disease, axonal, type 2z 30,934,157(-) G/T MISSENSE_VARIANT
640804 Uncertain Significance: Charcot-Marie-Tooth disease, axonal, type 2z 30,932,424(-) T/C MISSENSE_VARIANT
642355 Uncertain Significance: Charcot-Marie-Tooth disease, axonal, type 2z 30,941,940(-) T/C MISSENSE_VARIANT
642427 Uncertain Significance: Charcot-Marie-Tooth disease, axonal, type 2z 30,928,080(-) G/A MISSENSE_VARIANT
642714 Uncertain Significance: Charcot-Marie-Tooth disease, axonal, type 2z 30,936,932(-) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for MORC2 Gene

Structural Variations from Database of Genomic Variants (DGV) for MORC2 Gene

Variant ID Type Subtype PubMed ID
nsv1110864 OTHER inversion 24896259

Variation tolerance for MORC2 Gene

Residual Variation Intolerance Score: 2.11% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.95; 36.22% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MORC2 Gene

Human Gene Mutation Database (HGMD)
MORC2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MORC2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MORC2 Gene

Disorders for MORC2 Gene

MalaCards: The human disease database

(13) MalaCards diseases for MORC2 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
charcot-marie-tooth disease, axonal, type 2z
  • cmt2z
charcot-marie-tooth disease
  • peroneal muscular atrophy
charcot-marie-tooth hereditary neuropathy
  • charcot-marie-tooth disease
distal hereditary motor neuropathies
  • distal spinal muscular atrophy
charcot-marie-tooth disease/hereditary motor and sensory neuropathy
  • charcot-marie-tooth hereditary neuropathy
- elite association - COSMIC cancer census association via MalaCards
Search MORC2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MORC2_HUMAN
  • Charcot-Marie-Tooth disease 2Z (CMT2Z) [MIM:616688]: An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269 PubMed:26497905, ECO:0000269 PubMed:26659848, ECO:0000269 PubMed:28581500, ECO:0000269 PubMed:29440755}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for MORC2

genes like me logo Genes that share disorders with MORC2: view

No data available for Genatlas for MORC2 Gene

Publications for MORC2 Gene

  1. Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms. (PMID: 29440755) Douse CH … Modis Y (Nature communications 2018) 3 4 54
  2. Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators. (PMID: 29211708) Liu N … Wysocka J (Nature 2018) 3 4 54
  3. Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2. (PMID: 28581500) Tchasovnikarova IA … Lehner PJ (Nature genetics 2017) 3 4 54
  4. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. (PMID: 26497905) Sevilla T … Espinós C (Brain : a journal of neurology 2016) 3 4 54
  5. MORC2 mutations cause axonal Charcot-Marie-Tooth disease with pyramidal signs. (PMID: 26659848) Albulym OM … Nicholson GA (Annals of neurology 2016) 3 4 54

Products for MORC2 Gene

Sources for MORC2 Gene