The protein encoded by this gene is a zinc finger protein that localizes to the endoplasmic reticulum. The encoded protein binds an iron/sulfur cluster and may be involved in calcium homeostasis. Defects in this gene are a cause of Wolfram syndrome 2. [provided by RefSeq, Mar 2011] See more...

Aliases for CISD2 Gene

Aliases for CISD2 Gene

  • CDGSH Iron Sulfur Domain 2 2 3 5
  • Endoplasmic Reticulum Intermembrane Small Protein 2 3 4
  • Nutrient-Deprivation Autophagy Factor-1 2 3 4
  • CDGSH Iron-Sulfur Domain-Containing Protein 2 3 4
  • Zinc Finger, CDGSH-Type Domain 2 2 3
  • MitoNEET-Related 1 Protein 3 4
  • Miner1 3 4
  • NAF-1 3 4
  • ZCD2 3 4
  • ERIS 3 4
  • MitoNEET Related 1 2
  • Wolfram Syndrome 2 2
  • CDGSH2 4
  • WFS2 3

External Ids for CISD2 Gene

Previous HGNC Symbols for CISD2 Gene

  • ZCD2
  • WFS2

Previous GeneCards Identifiers for CISD2 Gene

  • GC04P104010
  • GC04P103790
  • GC04P099526
  • GC04P102829

Summaries for CISD2 Gene

Entrez Gene Summary for CISD2 Gene

  • The protein encoded by this gene is a zinc finger protein that localizes to the endoplasmic reticulum. The encoded protein binds an iron/sulfur cluster and may be involved in calcium homeostasis. Defects in this gene are a cause of Wolfram syndrome 2. [provided by RefSeq, Mar 2011]

GeneCards Summary for CISD2 Gene

CISD2 (CDGSH Iron Sulfur Domain 2) is a Protein Coding gene. Diseases associated with CISD2 include Wolfram Syndrome 2 and Wolfram Syndrome. Among its related pathways are Glucose / Energy Metabolism. Gene Ontology (GO) annotations related to this gene include 2 iron, 2 sulfur cluster binding. An important paralog of this gene is CISD1.

UniProtKB/Swiss-Prot Summary for CISD2 Gene

  • Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.

Additional gene information for CISD2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CISD2 Gene

Genomics for CISD2 Gene

GeneHancer (GH) Regulatory Elements for CISD2 Gene

Promoters and enhancers for CISD2 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 CISD2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CISD2

Top Transcription factor binding sites by QIAGEN in the CISD2 gene promoter:
  • CREB
  • deltaCREB
  • E2F
  • E2F-1
  • HSF2
  • MRF-2
  • NF-E2
  • NF-E2 p45
  • USF-1
  • USF1

Genomic Locations for CISD2 Gene

Genomic Locations for CISD2 Gene
chr4:102,868,974-102,892,807
(GRCh38/hg38)
Size:
23,834 bases
Orientation:
Plus strand
chr4:103,790,135-103,813,964
(GRCh37/hg19)
Size:
23,830 bases
Orientation:
Plus strand

Genomic View for CISD2 Gene

Genes around CISD2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CISD2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CISD2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CISD2 Gene

Proteins for CISD2 Gene

  • Protein details for CISD2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N5K1-CISD2_HUMAN
    Recommended name:
    CDGSH iron-sulfur domain-containing protein 2
    Protein Accession:
    Q8N5K1
    Secondary Accessions:
    • Q7Z3D5

    Protein attributes for CISD2 Gene

    Size:
    135 amino acids
    Molecular mass:
    15278 Da
    Cofactor:
    Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:49601;
    Quaternary structure:
    • Homodimer. Interacts with BCL2; the interaction is direct and disrupted by BIK interaction with BCL2. Interacts with BCL2L1. Interacts with ITPR1.
    SequenceCaution:
    • Sequence=CAD97935.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CISD2 Gene

neXtProt entry for CISD2 Gene

Post-translational modifications for CISD2 Gene

  • Ubiquitination at Lys19 and Lys95
  • Modification sites at PhosphoSitePlus

Other Protein References for CISD2 Gene

No data available for DME Specific Peptides for CISD2 Gene

Domains & Families for CISD2 Gene

Gene Families for CISD2 Gene

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

Protein Domains for CISD2 Gene

Suggested Antigen Peptide Sequences for CISD2 Gene

GenScript: Design optimal peptide antigens:
  • Nutrient-deprivation autophagy factor-1 (CISD2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N5K1

UniProtKB/Swiss-Prot:

CISD2_HUMAN :
  • Belongs to the CISD protein family. CISD2 subfamily.
Family:
  • Belongs to the CISD protein family. CISD2 subfamily.
genes like me logo Genes that share domains with CISD2: view

Function for CISD2 Gene

Molecular function for CISD2 Gene

UniProtKB/Swiss-Prot Function:
Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Redox potential: E is 0 +/- 10 mV for 2Fe-2S at pH 7.5. {ECO:0000269 PubMed:19580816};

Phenotypes From GWAS Catalog for CISD2 Gene

Gene Ontology (GO) - Molecular Function for CISD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22658674
GO:0005515 protein binding IPI 20010695
GO:0042803 protein homodimerization activity IDA 19580816
GO:0046872 metal ion binding IEA --
GO:0051536 iron-sulfur cluster binding IEA --
genes like me logo Genes that share ontologies with CISD2: view
genes like me logo Genes that share phenotypes with CISD2: view

Human Phenotype Ontology for CISD2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CISD2 Gene

MGI Knock Outs for CISD2:
  • Cisd2 Cisd2<tm1Tfts>
  • Cisd2 Cisd2<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for CISD2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CISD2 Gene

Localization for CISD2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CISD2 Gene

Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion outer membrane; Single-pass membrane protein. Note=According to PubMed:20010695, it mainly localizes to the endoplasmic reticulum. However, experiments in mouse showed that it mainly localizes to the mitochondrion outer membrane.

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 CISD2 gene
Compartment Confidence
mitochondrion 5
endoplasmic reticulum 5
extracellular 2
cytosol 2
plasma membrane 1
cytoskeleton 1
nucleus 1
endosome 1
lysosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CISD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005741 mitochondrial outer membrane ISS --
GO:0005783 endoplasmic reticulum IDA --
GO:0005789 endoplasmic reticulum membrane IEA,IDA 20010695
GO:0016020 membrane IEA,HDA 19946888
genes like me logo Genes that share ontologies with CISD2: view

Pathways & Interactions for CISD2 Gene

PathCards logo

SuperPathways for CISD2 Gene

SuperPathway Contained pathways
1 Glucose / Energy Metabolism
genes like me logo Genes that share pathways with CISD2: view

Pathways by source for CISD2 Gene

1 Cell Signaling Technology pathway for CISD2 Gene

Gene Ontology (GO) - Biological Process for CISD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000422 autophagy of mitochondrion IEA --
GO:0006914 autophagy IEA --
GO:0010259 multicellular organism aging ISS,IEA --
GO:0010506 regulation of autophagy IMP 20010695
genes like me logo Genes that share ontologies with CISD2: view

No data available for SIGNOR curated interactions for CISD2 Gene

Drugs & Compounds for CISD2 Gene

(2) Drugs for CISD2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Iron Approved, Experimental Pharma 1496
Calcium Approved Nutra 7884
genes like me logo Genes that share compounds with CISD2: view

Transcripts for CISD2 Gene

mRNA/cDNA for CISD2 Gene

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

CRISPR Products

Clone Products

  • Addgene plasmids for CISD2

Alternative Splicing Database (ASD) splice patterns (SP) for CISD2 Gene

No ASD Table

Relevant External Links for CISD2 Gene

GeneLoc Exon Structure for
CISD2

Expression for CISD2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CISD2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CISD2 Gene

This gene is overexpressed in Nasal epithelium (24.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CISD2 Gene



Protein tissue co-expression partners for CISD2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CISD2

SOURCE GeneReport for Unigene cluster for CISD2 Gene:

Hs.745013

mRNA Expression by UniProt/SwissProt for CISD2 Gene:

Q8N5K1-CISD2_HUMAN
Tissue specificity: Testis, small intestine, kidney, lung, brain, heart, pancreas and platelets.

Evidence on tissue expression from TISSUES for CISD2 Gene

  • Eye(4.2)
  • Nervous system(3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CISD2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • hypothalamus
  • mouth
  • neck
  • pharynx
  • pituitary gland
  • thyroid
Thorax:
  • esophagus
  • heart
  • heart valve
  • lung
Abdomen:
  • adrenal gland
  • intestine
  • kidney
  • large intestine
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • testicle
  • ureter
  • urethra
  • urinary bladder
  • uterus
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • toe
  • upper limb
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • sweat gland
  • white blood cell
genes like me logo Genes that share expression patterns with CISD2: view

No data available for mRNA differential expression in normal tissues for CISD2 Gene

Orthologs for CISD2 Gene

This gene was present in the common ancestor of animals.

Orthologs for CISD2 Gene

Organism Taxonomy Gene Similarity Type Details
oppossum
(Monodelphis domestica)
Mammalia CISD2 31
  • 100 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia CISD2 31 30
  • 99.51 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CISD2 31
  • 99 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CISD2 31
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CISD2 31 30
  • 93.83 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cisd2 30
  • 86.42 (n)
mouse
(Mus musculus)
Mammalia Cisd2 17 31 30
  • 86.17 (n)
chicken
(Gallus gallus)
Aves CISD2 31 30
  • 83.83 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cisd2 30
  • 77.04 (n)
zebrafish
(Danio rerio)
Actinopterygii cisd2 31 30
  • 67.41 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG1458 31 30
  • 49.87 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004484 30
  • 45.29 (n)
worm
(Caenorhabditis elegans)
Secernentea W02B12.15 31
  • 34 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2896 31
  • 41 (a)
OneToMany
Species where no ortholog for CISD2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • 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 CISD2 Gene

ENSEMBL:
Gene Tree for CISD2 (if available)
TreeFam:
Gene Tree for CISD2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CISD2: view image

Paralogs for CISD2 Gene

Paralogs for CISD2 Gene

(1) SIMAP similar genes for CISD2 Gene using alignment to 3 proteins:

  • CISD2_HUMAN
  • D6RCF4_HUMAN
  • I3L1N9_HUMAN

Pseudogenes.org Pseudogenes for CISD2 Gene

genes like me logo Genes that share paralogs with CISD2: view

Variants for CISD2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CISD2 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
638297 Pathogenic: Wolfram syndrome 2 102,869,188(+) G/A SPLICE_DONOR_VARIANT
716908 Benign: not provided 102,885,207(+) C/A NON_CODING_TRANSCRIPT_VARIANT,THREE_PRIME_UTR_VARIANT,INTRON_VARIANT
731902 Likely Benign: not provided 102,869,136(+) C/T SYNONYMOUS_VARIANT
745094 Likely Benign: not provided 102,885,406(+) T/C SYNONYMOUS_VARIANT,INTRON_VARIANT
749103 Benign: not provided 102,869,144(+) G/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for CISD2 Gene

Structural Variations from Database of Genomic Variants (DGV) for CISD2 Gene

Variant ID Type Subtype PubMed ID
esv2678594 CNV deletion 23128226
esv2759270 CNV gain 17122850
esv3569635 CNV loss 25503493
nsv461598 CNV loss 19166990
nsv528680 CNV loss 19592680
nsv594957 CNV loss 21841781
nsv594978 CNV loss 21841781
nsv950370 CNV duplication 24416366
nsv966304 CNV duplication 23825009

Variation tolerance for CISD2 Gene

Residual Variation Intolerance Score: 43.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.15; 39.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CISD2 Gene

Human Gene Mutation Database (HGMD)
CISD2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CISD2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CISD2 Gene

Disorders for CISD2 Gene

MalaCards: The human disease database

(8) MalaCards diseases for CISD2 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search CISD2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CISD2_HUMAN
  • Wolfram syndrome 2 (WFS2) [MIM:604928]: A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent. {ECO:0000269 PubMed:17846994}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CISD2

genes like me logo Genes that share disorders with CISD2: view

No data available for Genatlas for CISD2 Gene

Publications for CISD2 Gene

  1. MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity. (PMID: 17376863) Wiley SE … Dixon JE (Proceedings of the National Academy of Sciences of the United States of America 2007) 2 3 4 54
  2. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. (PMID: 17846994) Amr S … Shiang R (American journal of human genetics 2007) 2 3 4 54
  3. Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. (PMID: 20010695) Chang NC … Shore GC (The EMBO journal 2010) 3 4 54
  4. Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. (PMID: 19580816) Conlan AR … Paddock ML (Journal of molecular biology 2009) 3 4 54
  5. The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster. (PMID: 17584744) Wiley SE … Dixon JE (The Journal of biological chemistry 2007) 2 3 54

Products for CISD2 Gene

Sources for CISD2 Gene