The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010] See more...

Aliases for NHLRC1 Gene

Aliases for NHLRC1 Gene

  • NHL Repeat Containing E3 Ubiquitin Protein Ligase 1 2 3 5
  • RING-Type E3 Ubiquitin Transferase NHLRC1 3 4
  • E3 Ubiquitin-Protein Ligase NHLRC1 3 4
  • NHL Repeat-Containing Protein 1 3 4
  • NHL Repeat Containing 1 2 3
  • Malin 2 4
  • EPM2B 3 4
  • Epilepsy, Progressive Myoclonus Type 2B 2
  • EC 2.3.2.27 4
  • BA204B7.2 3
  • EPM2A 3
  • MALIN 3

External Ids for NHLRC1 Gene

Previous GeneCards Identifiers for NHLRC1 Gene

  • GC00U913226
  • GC06U900282
  • GC06M018228
  • GC06M018120

Summaries for NHLRC1 Gene

Entrez Gene Summary for NHLRC1 Gene

  • The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]

GeneCards Summary for NHLRC1 Gene

NHLRC1 (NHL Repeat Containing E3 Ubiquitin Protein Ligase 1) is a Protein Coding gene. Diseases associated with NHLRC1 include Myoclonic Epilepsy Of Lafora and Epilepsy. Among its related pathways are Metabolism and Glycosaminoglycan metabolism. Gene Ontology (GO) annotations related to this gene include ligase activity and ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot Summary for NHLRC1 Gene

  • E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway.

Gene Wiki entry for NHLRC1 Gene

Additional gene information for NHLRC1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NHLRC1 Gene

Genomics for NHLRC1 Gene

GeneHancer (GH) Regulatory Elements for NHLRC1 Gene

Promoters and enhancers for NHLRC1 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 NHLRC1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NHLRC1

Top Transcription factor binding sites by QIAGEN in the NHLRC1 gene promoter:
  • AML1a
  • Bach2
  • c-Myc
  • Elk-1
  • HEN1
  • HOXA5
  • Max1
  • p53
  • YY1

Genomic Locations for NHLRC1 Gene

Genomic Locations for NHLRC1 Gene
chr6:18,120,440-18,122,677
(GRCh38/hg38)
Size:
2,238 bases
Orientation:
Minus strand
chr6:18,120,718-18,122,851
(GRCh37/hg19)
Size:
2,134 bases
Orientation:
Minus strand

Genomic View for NHLRC1 Gene

Genes around NHLRC1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NHLRC1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NHLRC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NHLRC1 Gene

Proteins for NHLRC1 Gene

  • Protein details for NHLRC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6VVB1-NHLC1_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase NHLRC1
    Protein Accession:
    Q6VVB1
    Secondary Accessions:
    • Q3SYB1
    • Q5VUK7
    • Q6IMH1

    Protein attributes for NHLRC1 Gene

    Size:
    395 amino acids
    Molecular mass:
    42293 Da
    Quaternary structure:
    • Interacts with AGL. Interacts (via the NHL repeats) with EPM2A/laforin. Forms a complex with EPM2A/laforin and HSP70. Interacts with PRDM8 (PubMed:22961547).

neXtProt entry for NHLRC1 Gene

Post-translational modifications for NHLRC1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NHLRC1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NHLRC1 Gene

Domains & Families for NHLRC1 Gene

Gene Families for NHLRC1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for NHLRC1 Gene

Suggested Antigen Peptide Sequences for NHLRC1 Gene

GenScript: Design optimal peptide antigens:
  • NHL repeat-containing protein 1 (NHLC1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6VVB1

UniProtKB/Swiss-Prot:

NHLC1_HUMAN :
  • The RING domain is essential for ubiquitin E3 ligase activity.
Domain:
  • The RING domain is essential for ubiquitin E3 ligase activity.
genes like me logo Genes that share domains with NHLRC1: view

Function for NHLRC1 Gene

Molecular function for NHLRC1 Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;.

Enzyme Numbers (IUBMB) for NHLRC1 Gene

Phenotypes From GWAS Catalog for NHLRC1 Gene

Gene Ontology (GO) - Molecular Function for NHLRC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA,EXP 15930137
GO:0005515 protein binding IPI 15930137
GO:0016740 transferase activity IEA --
GO:0046872 metal ion binding IEA --
GO:0061630 ubiquitin protein ligase activity IBA,IEA 21873635
genes like me logo Genes that share ontologies with NHLRC1: view
genes like me logo Genes that share phenotypes with NHLRC1: view

Human Phenotype Ontology for NHLRC1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NHLRC1 Gene

MGI Knock Outs for NHLRC1:

Animal Model Products

CRISPR Products

miRNA for NHLRC1 Gene

miRTarBase miRNAs that target NHLRC1

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for NHLRC1 Gene

Localization for NHLRC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NHLRC1 Gene

Endoplasmic reticulum. Nucleus. Note=Localizes at the endoplasmic reticulum and, to a lesser extent, in the nucleus.

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 NHLRC1 gene
Compartment Confidence
nucleus 5
endoplasmic reticulum 5
cytosol 4
mitochondrion 2
lysosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NHLRC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 17908927
GO:0005783 endoplasmic reticulum IEA --
GO:0005829 cytosol TAS --
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with NHLRC1: view

Pathways & Interactions for NHLRC1 Gene

genes like me logo Genes that share pathways with NHLRC1: view

Pathways by source for NHLRC1 Gene

1 KEGG pathway for NHLRC1 Gene

UniProtKB/Swiss-Prot Q6VVB1-NHLC1_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for NHLRC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IDA 15930137
GO:0001932 regulation of protein phosphorylation IEA --
GO:0005977 glycogen metabolic process IEA --
GO:0005978 glycogen biosynthetic process IEA,TAS --
GO:0006914 autophagy IEA --
genes like me logo Genes that share ontologies with NHLRC1: view

No data available for SIGNOR curated interactions for NHLRC1 Gene

Drugs & Compounds for NHLRC1 Gene

(1) Additional Compounds for NHLRC1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NHLRC1: view

Transcripts for NHLRC1 Gene

mRNA/cDNA for NHLRC1 Gene

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

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NHLRC1 Gene

No ASD Table

Relevant External Links for NHLRC1 Gene

GeneLoc Exon Structure for
NHLRC1

Expression for NHLRC1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NHLRC1 Gene

Protein differential expression in normal tissues from HIPED for NHLRC1 Gene

This gene is overexpressed in Platelet (61.6) and Retina (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NHLRC1 Gene



Protein tissue co-expression partners for NHLRC1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NHLRC1

SOURCE GeneReport for Unigene cluster for NHLRC1 Gene:

Hs.348351

mRNA Expression by UniProt/SwissProt for NHLRC1 Gene:

Q6VVB1-NHLC1_HUMAN
Tissue specificity: Expressed in brain, cerebellum, spinal cord, medulla, heart, liver, skeletal muscle and pancreas.

Evidence on tissue expression from TISSUES for NHLRC1 Gene

  • Nervous system(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NHLRC1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • head
Abdomen:
  • liver
General:
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with NHLRC1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for NHLRC1 Gene

Orthologs for NHLRC1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NHLRC1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NHLRC1 31 30
  • 99.58 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NHLRC1 31 30
  • 86.92 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NHLRC1 31 30
  • 85.67 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Nhlrc1 17 31 30
  • 82.37 (n)
rat
(Rattus norvegicus)
Mammalia Nhlrc1 30
  • 81.8 (n)
oppossum
(Monodelphis domestica)
Mammalia NHLRC1 31
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NHLRC1 31
  • 54 (a)
OneToOne
chicken
(Gallus gallus)
Aves NHLRC1 31 30
  • 62.35 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NHLRC1 31
  • 55 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nhlrc1 30
  • 52.65 (n)
Species where no ortholog for NHLRC1 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 squirt (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)
  • zebrafish (Danio rerio)

Evolution for NHLRC1 Gene

ENSEMBL:
Gene Tree for NHLRC1 (if available)
TreeFam:
Gene Tree for NHLRC1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NHLRC1: view image

Paralogs for NHLRC1 Gene

No data available for Paralogs for NHLRC1 Gene

Variants for NHLRC1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NHLRC1 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
648810 Uncertain Significance: Lafora disease 18,122,032(-) T/A MISSENSE_VARIANT
650494 Uncertain Significance: Lafora disease 18,122,338(-) A/G MISSENSE_VARIANT
652203 Uncertain Significance: Lafora disease 18,122,392(-) C/T MISSENSE_VARIANT
656381 Uncertain Significance: Lafora disease 18,122,122(-) T/G MISSENSE_VARIANT
662633 Uncertain Significance: Lafora disease 18,122,137(-) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for NHLRC1 Gene

Structural Variations from Database of Genomic Variants (DGV) for NHLRC1 Gene

Variant ID Type Subtype PubMed ID
nsv1034755 CNV loss 25217958
nsv601049 CNV gain 21841781
nsv830597 CNV loss 17160897

Variation tolerance for NHLRC1 Gene

Residual Variation Intolerance Score: 69.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.70; 86.52% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NHLRC1 Gene

Human Gene Mutation Database (HGMD)
NHLRC1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NHLRC1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NHLRC1 Gene

Disorders for NHLRC1 Gene

MalaCards: The human disease database

(20) MalaCards diseases for NHLRC1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
myoclonic epilepsy of lafora
  • melf
epilepsy
  • epilepsy syndrome
neuroleptic malignant syndrome
progressive myoclonus epilepsy
  • progressive myoclonic epilepsy
progressive myoclonus epilepsy, lafora type
  • myoclonic epilepsy of lafora
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

NHLC1_HUMAN
  • Epilepsy, progressive myoclonic 2 (EPM2) [MIM:254780]: An autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum. {ECO:0000269 PubMed:12958597, ECO:0000269 PubMed:15781812, ECO:0000269 PubMed:15930137, ECO:0000269 PubMed:16021330, ECO:0000269 PubMed:18311786, ECO:0000269 PubMed:21505799}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NHLRC1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NHLRC1: view

No data available for Genatlas for NHLRC1 Gene

Publications for NHLRC1 Gene

  1. Mutations in NHLRC1 cause progressive myoclonus epilepsy. (PMID: 12958597) Chan EM … Scherer SW (Nature genetics 2003) 2 3 4 23 54
  2. The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system. (PMID: 19036738) Garyali P … Ganesh S (Human molecular genetics 2009) 3 4 23 54
  3. Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes. (PMID: 19267391) Singh S … Ganesh S (Human mutation 2009) 3 23 41 54
  4. Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG). (PMID: 18070875) Worby CA … Dixon JE (The Journal of biological chemistry 2008) 3 4 23 54
  5. Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin. (PMID: 18311786) Singh S … Ganesh S (Human mutation 2008) 3 4 23 54

Products for NHLRC1 Gene

Sources for NHLRC1 Gene