This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternat... See more...

Aliases for SIL1 Gene

Aliases for SIL1 Gene

  • SIL1 Nucleotide Exchange Factor 2 3 5
  • BAP 2 3 4
  • Nucleotide Exchange Factor SIL1 3 4
  • BiP-Associated Protein 3 4
  • ULG5 2 3
  • SIL1 Homolog, Endoplasmic Reticulum Chaperone (S. Cerevisiae) 2
  • SIL1-Like Protein Endoplasmic Reticulum Chaperone 3
  • SIL1 Homolog, Endoplasmic Reticulum Chaperone 3
  • Marinesco-Sjogren Syndrome 2
  • SIL1 5
  • MSS 3

External Ids for SIL1 Gene

Previous HGNC Symbols for SIL1 Gene

  • MSS

Previous GeneCards Identifiers for SIL1 Gene

  • GC05M138157
  • GC05M138313
  • GC05M138358
  • GC05M138310
  • GC05M133472
  • GC05M138282

Summaries for SIL1 Gene

Entrez Gene Summary for SIL1 Gene

  • This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

GeneCards Summary for SIL1 Gene

SIL1 (SIL1 Nucleotide Exchange Factor) is a Protein Coding gene. Diseases associated with SIL1 include Marinesco-Sjogren Syndrome and Apraxia. Among its related pathways are Protein processing in endoplasmic reticulum. Gene Ontology (GO) annotations related to this gene include binding and unfolded protein binding. An important paralog of this gene is HSPBP1.

UniProtKB/Swiss-Prot Summary for SIL1 Gene

  • Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5.

Gene Wiki entry for SIL1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SIL1 Gene

Genomics for SIL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SIL1 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 SIL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIL1

Top Transcription factor binding sites by QIAGEN in the SIL1 gene promoter:
  • HOXA9
  • HOXA9B
  • Meis-1
  • Meis-1b
  • POU2F1
  • POU2F1a
  • STAT1

Genomic Locations for SIL1 Gene

Genomic Locations for SIL1 Gene
chr5:138,946,724-139,293,557
(GRCh38/hg38)
Size:
346,834 bases
Orientation:
Minus strand
chr5:138,282,409-138,629,246
(GRCh37/hg19)
Size:
346,838 bases
Orientation:
Minus strand

Genomic View for SIL1 Gene

Genes around SIL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIL1 Gene

Proteins for SIL1 Gene

  • Protein details for SIL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H173-SIL1_HUMAN
    Recommended name:
    Nucleotide exchange factor SIL1
    Protein Accession:
    Q9H173
    Secondary Accessions:
    • D3DQC2
    • Q8N2L3

    Protein attributes for SIL1 Gene

    Size:
    461 amino acids
    Molecular mass:
    52085 Da
    Quaternary structure:
    • Interacts with HSPA5.

neXtProt entry for SIL1 Gene

Post-translational modifications for SIL1 Gene

  • N-glycosylated.
  • Glycosylation at Thr41, Ser46, Ser47, Thr48, Thr97, Thr127, Ser128, Asn193, and Asn236
  • Ubiquitination at Lys309
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

No data available for DME Specific Peptides for SIL1 Gene

Domains & Families for SIL1 Gene

Gene Families for SIL1 Gene

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

Protein Domains for SIL1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SIL1 Gene

GenScript: Design optimal peptide antigens:
  • Endoplasmic reticulum chaperone SIL1 (A0RZB6_HUMAN)
  • Endoplasmic reticulum chaperone (A0RZG6_HUMAN)
  • BiP-associated protein (SIL1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H173

UniProtKB/Swiss-Prot:

SIL1_HUMAN :
  • Belongs to the SIL1 family.
Family:
  • Belongs to the SIL1 family.
genes like me logo Genes that share domains with SIL1: view

Function for SIL1 Gene

Molecular function for SIL1 Gene

UniProtKB/Swiss-Prot Function:
Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5.

Phenotypes From GWAS Catalog for SIL1 Gene

Gene Ontology (GO) - Molecular Function for SIL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000774 adenyl-nucleotide exchange factor activity IBA --
GO:0005515 protein binding IPI 25416956
GO:0051082 unfolded protein binding NAS 11101517
genes like me logo Genes that share ontologies with SIL1: view
genes like me logo Genes that share phenotypes with SIL1: view

Human Phenotype Ontology for SIL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

miRNA for SIL1 Gene

miRTarBase miRNAs that target SIL1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIL1

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for SIL1 Gene

Localization for SIL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIL1 Gene

Endoplasmic reticulum lumen.

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 SIL1 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 4
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
cytosol 2
golgi apparatus 2
peroxisome 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for SIL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space HDA 16502470
GO:0005737 cytoplasm IBA --
GO:0005783 endoplasmic reticulum IBA,NAS 11101517
GO:0005788 endoplasmic reticulum lumen IEA --
genes like me logo Genes that share ontologies with SIL1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SIL1 Gene

Pathways & Interactions for SIL1 Gene

PathCards logo

SuperPathways for SIL1 Gene

genes like me logo Genes that share pathways with SIL1: view

Pathways by source for SIL1 Gene

1 KEGG pathway for SIL1 Gene

SIGNOR curated interactions for SIL1 Gene

Activates:

Gene Ontology (GO) - Biological Process for SIL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006457 protein folding NAS 11101517
GO:0006886 intracellular protein transport NAS 11101517
GO:0015031 protein transport IEA --
GO:0050790 regulation of catalytic activity IEA --
genes like me logo Genes that share ontologies with SIL1: view

Drugs & Compounds for SIL1 Gene

(1) Drugs for SIL1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for SIL1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SIL1: view

Transcripts for SIL1 Gene

mRNA/cDNA for SIL1 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIL1

Alternative Splicing Database (ASD) splice patterns (SP) for SIL1 Gene

No ASD Table

Relevant External Links for SIL1 Gene

GeneLoc Exon Structure for
SIL1

Expression for SIL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SIL1 Gene

Protein differential expression in normal tissues from HIPED for SIL1 Gene

This gene is overexpressed in Milk (29.5) and Testis (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SIL1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SIL1

SOURCE GeneReport for Unigene cluster for SIL1 Gene:

Hs.483521

mRNA Expression by UniProt/SwissProt for SIL1 Gene:

Q9H173-SIL1_HUMAN
Tissue specificity: Highly expressed in tissues which produce large amounts of secreted proteins such as kidney, liver and placenta. Also expressed in colon, heart, lung, ovary, pancreas, peripheral leukocyte, prostate, spleen and thymus. Expressed at low levels throughout the brain.

Evidence on tissue expression from TISSUES for SIL1 Gene

  • Skin(4.7)
  • Liver(4.6)
  • Intestine(3.6)
  • Lung(3.5)
  • Nervous system(3.2)
  • Lymph node(3.2)
  • Thyroid gland(3.1)
  • Blood(3)
  • Muscle(2.9)
  • Stomach(2.9)
  • Heart(2.8)
  • Kidney(2.6)
  • Pancreas(2.6)
  • Gall bladder(2.3)
  • Bone marrow(2.3)
  • Spleen(2.3)
  • Adrenal gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SIL1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • eye
  • head
  • pituitary gland
  • skull
Thorax:
  • breast
  • chest wall
  • lung
  • rib
  • rib cage
  • sternum
Pelvis:
  • ovary
  • pelvis
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vulva
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shoulder
  • thigh
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with SIL1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein tissue co-expression partners for SIL1 Gene

Orthologs for SIL1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SIL1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SIL1 30 31
  • 99.19 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SIL1 30 31
  • 89.57 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SIL1 30 31
  • 87.26 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sil1 30
  • 85.39 (n)
Mouse
(Mus musculus)
Mammalia Sil1 30 17 31
  • 84.96 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SIL1 31
  • 70 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SIL1 31
  • 50 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SIL1 30 31
  • 67.61 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SIL1 31
  • 57 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia sil1 30
  • 56.95 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC568308 30
  • 58.25 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003488 30
  • 48.3 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG10420 30 31 32
  • 45.71 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SIL1 33
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 35 (a)
OneToOne
Species where no ortholog for SIL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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)
  • 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 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 SIL1 Gene

ENSEMBL:
Gene Tree for SIL1 (if available)
TreeFam:
Gene Tree for SIL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SIL1: view image

Paralogs for SIL1 Gene

Paralogs for SIL1 Gene

genes like me logo Genes that share paralogs with SIL1: view

Variants for SIL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIL1 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
2622 Pathogenic: Marinesco-Sjögren syndrome 139,026,936(-) G/GTCTT FRAMESHIFT_VARIANT
2623 Pathogenic: Marinesco-Sjögren syndrome 139,026,800(-) C/T SPLICE_DONOR_VARIANT
2624 Likely Pathogenic: Marinesco-Sjögren syndrome 139,026,799(-) A/G SPLICE_DONOR_VARIANT
2625 Pathogenic: Marinesco-Sjögren syndrome 139,050,960(-) G/A NONSENSE
2626 Pathogenic: Marinesco-Sjögren syndrome 138,951,170(-) C/T SPLICE_DONOR_VARIANT

Additional dbSNP identifiers (rs#s) for SIL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for SIL1 Gene

Variant ID Type Subtype PubMed ID
esv2666199 CNV deletion 23128226
esv2672987 CNV deletion 23128226
esv3408136 CNV insertion 20981092
esv3447133 CNV duplication 20981092
esv3566707 CNV deletion 23714750
esv3566709 CNV deletion 23714750
esv3606932 CNV loss 21293372
esv3606933 CNV loss 21293372
esv3606935 CNV gain 21293372
esv3606936 CNV loss 21293372
nsv1017883 CNV gain 25217958
nsv1029030 CNV gain 25217958
nsv1137028 CNV deletion 24896259
nsv1140572 CNV deletion 24896259
nsv436490 CNV deletion 17901297
nsv5027 CNV insertion 18451855
nsv950408 CNV deletion 24416366
nsv968249 CNV duplication 23825009

Variation tolerance for SIL1 Gene

Residual Variation Intolerance Score: 74.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.99; 60.13% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SIL1 Gene

Human Gene Mutation Database (HGMD)
SIL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIL1 Gene

Disorders for SIL1 Gene

MalaCards: The human disease database

(28) MalaCards diseases for SIL1 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
marinesco-sjogren syndrome
  • mss
apraxia
  • dyspraxia
cataract
  • cataracts
rare disorder with lens opacification
  • rare cataract
constipation
- elite association - COSMIC cancer census association via MalaCards
Search SIL1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SIL1_HUMAN
  • Marinesco-Sjoegren syndrome (MSS) [MIM:248800]: Autosomal recessive multisystem disorder which is characterized by cerebellar ataxia due to cerebellar atrophy, with Purkinje and granule cell loss and myopathy featuring marked muscle replacement with fat and connective tissue. Other cardinal features include bilateral cataracts, hypergonadotrophic hypogonadism and mild to severe mental retardation. Skeletal abnormalities, short stature, dysarthria, strabismus and nystagmus are also frequent findings. Mutational inactivation of this protein may result in ER stress-induced cell death signaling or malfunctioning chaperone machineries that mishandle client proteins which are critical for the organs targeted in MSS. {ECO:0000269 PubMed:16282977, ECO:0000269 PubMed:16282978}. Note=The disease is caused by mutations affecting the gene represented in this entry.
genes like me logo Genes that share disorders with SIL1: view

No data available for Genatlas for SIL1 Gene

Publications for SIL1 Gene

  1. Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy. (PMID: 16282977) Senderek J … Zerres K (Nature genetics 2005) 2 3 4 23
  2. The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone. (PMID: 16282978) Anttonen AK … Lehesjoki AE (Nature genetics 2005) 3 4 23
  3. BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP. (PMID: 12356756) Chung KT … Hendershot LM (The Journal of biological chemistry 2002) 2 3 4
  4. LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum. (PMID: 11101517) Tyson JR … Stirling CJ (The EMBO journal 2000) 2 3 4
  5. Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjögren syndrome. (PMID: 20111056) Takahata T … Kitaoka T (Journal of human genetics 2010) 3 23

Products for SIL1 Gene

Sources for SIL1 Gene