This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of no... See more...

Aliases for DIABLO Gene

Aliases for DIABLO Gene

  • Diablo IAP-Binding Mitochondrial Protein 2 3 5
  • Second Mitochondria-Derived Activator Of Caspase 2 3 4
  • Direct IAP-Binding Protein With Low PI 3 4
  • Diablo Homolog, Mitochondrial 3 4
  • SMAC 3 4
  • Diablo, IAP-Binding Mitochondrial Protein 2
  • Diablo-Like Protein 3
  • DFNA64 3
  • Smac 4

External Ids for DIABLO Gene

Previous GeneCards Identifiers for DIABLO Gene

  • GC12M121129
  • GC12M121217
  • GC12M121258
  • GC12M122692
  • GC12M119654

Summaries for DIABLO Gene

Entrez Gene Summary for DIABLO Gene

  • This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of nonsyndromic deafness-64. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

GeneCards Summary for DIABLO Gene

DIABLO (Diablo IAP-Binding Mitochondrial Protein) is a Protein Coding gene. Diseases associated with DIABLO include Deafness, Autosomal Dominant 64 and Autosomal Dominant Non-Syndromic Sensorineural Deafness Type Dfna. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and TNFR1 Pathway.

UniProtKB/Swiss-Prot Summary for DIABLO Gene

  • Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.

Gene Wiki entry for DIABLO Gene

Additional gene information for DIABLO Gene

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

Genomics for DIABLO Gene

GeneHancer (GH) Regulatory Elements for DIABLO Gene

Promoters and enhancers for DIABLO Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J122222 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 750.6 +1.7 1678 6.3 SP1 ZBTB40 ZBTB6 MLX SMARCE1 RBPJ POLR2A USF2 NR2F1 ATF1 DIABLO LOC101593348 lnc-DIABLO-1 ZCCHC8 RSRC2 SETD1B PSMD9 KNTC1 KDM2B ABCB9
GH12J122208 Promoter 0.4 EPDnew 750.4 +19.4 19439 0.1 POLR2A DIABLO MLXIP B3GNT4 piR-31508-013 lnc-DIABLO-1 ENSG00000256861
GH12J122216 Promoter 0.3 EPDnew 750.4 +11.0 11028 0.1 DIABLO piR-31508-013 B3GNT4 lnc-DIABLO-1 ENSG00000256861
GH12J122229 Enhancer 0.2 Ensembl 750.6 -2.0 -1967 0.2 DIABLO lnc-DIABLO-1 lnc-CLIP1-1 VPS33A ENSG00000256861
GH12J122020 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.7 +204.7 204686 4.9 ZNF785 SIN3A ZNF24 ZBTB40 MLX USF2 CREB1 MIXL1 NFYC L3MBTL2 BCL7A WDR66 LINC01089 KNTC1 SETD1B PSMD9 VPS33A ZCCHC8 RSRC2 DIABLO
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DIABLO on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the DIABLO gene promoter:
  • AREB6
  • p53
  • STAT3

Genomic Locations for DIABLO Gene

Genomic Locations for DIABLO Gene
chr12:122,207,662-122,227,534
(GRCh38/hg38)
Size:
19,873 bases
Orientation:
Minus strand
chr12:122,692,209-122,712,081
(GRCh37/hg19)
Size:
19,873 bases
Orientation:
Minus strand

Genomic View for DIABLO Gene

Genes around DIABLO on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for DIABLO Gene

Proteins for DIABLO Gene

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

    Protein Symbol:
    Q9NR28-DBLOH_HUMAN
    Recommended name:
    Diablo homolog, mitochondrial
    Protein Accession:
    Q9NR28
    Secondary Accessions:
    • B2RDQ0
    • Q6W3F3
    • Q96LV0
    • Q9BT11
    • Q9HAV6

    Protein attributes for DIABLO Gene

    Size:
    239 amino acids
    Molecular mass:
    27131 Da
    Quaternary structure:
    • Homodimer. Interacts with BEX3 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2, XIAP/BIRC4, BIRC6/bruce and BIRC7/livin. Interacts with the monomeric and dimeric form of BIRC5/survivin.

    Three dimensional structures from OCA and Proteopedia for DIABLO Gene

    Alternative splice isoforms for DIABLO Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DIABLO Gene

Post-translational modifications for DIABLO Gene

  • Ubiquitinated by BIRC7/livin.
  • Ubiquitination at Lys123, Lys191, Lys203, and Lys207
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for DIABLO Gene

Domains & Families for DIABLO Gene

Gene Families for DIABLO Gene

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

Protein Domains for DIABLO Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DIABLO Gene

GenScript: Design optimal peptide antigens:
  • Second mitochondria-derived activator of caspase (DBLOH_HUMAN)
  • cDNA FLJ10537 fis, clone NT2RP2001119, highly similar to Diablo homolog, mitochondrial (Q502X2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NR28

UniProtKB/Swiss-Prot:

DBLOH_HUMAN :
  • The mature N-terminus mediates interaction with XIAP/BIRC4.
Domain:
  • The mature N-terminus mediates interaction with XIAP/BIRC4.
genes like me logo Genes that share domains with DIABLO: view

Function for DIABLO Gene

Molecular function for DIABLO Gene

UniProtKB/Swiss-Prot Function:
Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.

Phenotypes From GWAS Catalog for DIABLO Gene

Gene Ontology (GO) - Molecular Function for DIABLO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 11604410
genes like me logo Genes that share ontologies with DIABLO: view
genes like me logo Genes that share phenotypes with DIABLO: view

Human Phenotype Ontology for DIABLO Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for DIABLO Gene

MGI Knock Outs for DIABLO:

Animal Model Products

CRISPR Products

Clone Products

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

Localization for DIABLO Gene

Subcellular locations from UniProtKB/Swiss-Prot for DIABLO Gene

Mitochondrion. Note=Released into the cytosol when cells undergo apoptosis.

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 DIABLO gene
Compartment Confidence
mitochondrion 5
cytosol 5
plasma membrane 4
nucleus 3
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for DIABLO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IEA --
GO:0005758 mitochondrial intermembrane space TAS 18309324
GO:0005829 cytosol TAS --
GO:0009898 cytoplasmic side of plasma membrane ISS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with DIABLO: view

Pathways & Interactions for DIABLO Gene

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

Pathways by source for DIABLO Gene

1 R&D Systems pathway for DIABLO Gene
8 Qiagen pathways for DIABLO Gene
  • Apoptosis through Death Receptors
  • Apoptotic Pathways Triggered By HIV1
  • Caspase Cascade
  • Cellular Apoptosis Pathway
  • LT-BetaR Pathway
1 Cell Signaling Technology pathway for DIABLO Gene
1 GeneTex pathway for DIABLO Gene

SIGNOR curated interactions for DIABLO Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for DIABLO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process TAS,IEA 10929712
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process IEA,TAS 18309324
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors TAS 10950947
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress IBA 21873635
GO:0008635 activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c TAS,IBA 21873635
genes like me logo Genes that share ontologies with DIABLO: view

Drugs & Compounds for DIABLO Gene

(19) Drugs for DIABLO Gene - From: DrugBank, ApexBio, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phenethyl isothiocyanate Investigational Pharma Target 14
LCL161 Pharma Antagonist of IAPs inhibitor, Inhibitor of apoptosis proteins (IAPS) antagonist 0

(13) Additional Compounds for DIABLO Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) ApexBio Compounds for DIABLO Gene

Compound Action Cas Number
LCL161 Antagonist of IAPs inhibitor 1005342-46-0
genes like me logo Genes that share compounds with DIABLO: view

Transcripts for DIABLO Gene

CRISPR Products

Clone Products

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

ExUns: 1 ^ 2a · 2b ^ 3a · 3b · 3c · 3d · 3e · 3f ^ 4 ^ 5a · 5b · 5c · 5d ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b · 11c · 11d · 11e ·
SP1: - - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - - - - -
SP4: - - - - - - -
SP5: - - - - - - - - - -
SP6: - - - - - - - - - -
SP7: - - - - - - - - - -
SP8: - -
SP9: - - - -
SP10: -
SP11:
SP12:
SP13: -
SP14: - -

ExUns: 11f · 11g · 11h · 11i · 11j
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:

Relevant External Links for DIABLO Gene

GeneLoc Exon Structure for
DIABLO
ECgene alternative splicing isoforms for
DIABLO

Expression for DIABLO Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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



Protein tissue co-expression partners for DIABLO Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of DIABLO Gene:

DIABLO

SOURCE GeneReport for Unigene cluster for DIABLO Gene:

Hs.169611

mRNA Expression by UniProt/SwissProt for DIABLO Gene:

Q9NR28-DBLOH_HUMAN
Tissue specificity: Ubiquitously expressed with highest expression in testis. Expression is also high in heart, liver, kidney, spleen, prostate and ovary. Low in brain, lung, thymus and peripheral blood leukocytes. Isoform 3 is ubiquitously expressed.

Evidence on tissue expression from TISSUES for DIABLO Gene

  • Liver(4.5)
  • Muscle(4.4)
  • Stomach(4.4)
  • Nervous system(4)
  • Intestine(2.5)
  • Lung(2.4)
  • Blood(2.3)
  • Kidney(2.3)
  • Heart(2.2)
  • Adrenal gland(2)
  • Bone marrow(2)
  • Lymph node(2)

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

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • head
  • inner ear
  • middle ear
  • outer ear
Thorax:
  • heart
  • heart valve
Limb:
  • forearm
General:
  • peripheral nerve
  • peripheral nervous system
genes like me logo Genes that share expression patterns with DIABLO: view

No data available for mRNA differential expression in normal tissues and Protein differential expression in normal tissues for DIABLO Gene

Orthologs for DIABLO Gene

This gene was present in the common ancestor of chordates.

Orthologs for DIABLO Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DIABLO 33 32
  • 99.44 (n)
OneToOne
dog
(Canis familiaris)
Mammalia DIABLO 33 32
  • 90.3 (n)
OneToOne
cow
(Bos Taurus)
Mammalia DIABLO 33 32
  • 88.61 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Diablo 17 33 32
  • 84.67 (n)
oppossum
(Monodelphis domestica)
Mammalia DIABLO 33
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DIABLO 33
  • 68 (a)
OneToOne
chicken
(Gallus gallus)
Aves DIABLO 33 32
  • 67.38 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DIABLO 33
  • 60 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia diablo 32
  • 59.53 (n)
Str.8735 32
zebrafish
(Danio rerio)
Actinopterygii diablob 33
  • 38 (a)
OneToMany
diabloa 33
  • 35 (a)
OneToMany
Species where no ortholog for DIABLO 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)
  • rat (Rattus norvegicus)
  • 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)

Evolution for DIABLO Gene

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

Paralogs for DIABLO Gene

No data available for Paralogs for DIABLO Gene

Variants for DIABLO Gene

Sequence variations from dbSNP and Humsavar for DIABLO Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs137928955 benign-likely-benign, not specified 122,216,877(-) T/C intron_variant
rs387906893 pathogenic, Deafness, autosomal dominant 64, not provided, Deafness, autosomal dominant, 64 (DFNA64) [MIM:614152] 122,216,808(-) G/A coding_sequence_variant, missense_variant
rs370571609 conflicting-interpretations-of-pathogenicity, not specified 122,218,260(-) A/T intron_variant
rs1223091168 likely-benign, not specified 122,208,441(-) T/C coding_sequence_variant, synonymous_variant
rs149387774 likely-benign, not specified 122,208,555(-) G/A/C coding_sequence_variant, synonymous_variant

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

Variant ID Type Subtype PubMed ID
esv2659676 CNV deletion 23128226
esv3630970 CNV loss 21293372
nsv1134269 CNV deletion 24896259
nsv475807 CNV novel sequence insertion 20440878

Variation tolerance for DIABLO Gene

Residual Variation Intolerance Score: 63% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.98; 20.26% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DIABLO Gene

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

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

Disorders for DIABLO Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
deafness, autosomal dominant 64
  • dfna64
autosomal dominant non-syndromic sensorineural deafness type dfna
  • autosomal dominant isolated neurosensory deafness type dfna
myasthenic syndrome, congenital, 13
  • cms13
fanconi anemia, complementation group f
  • fancf
patellar tendinitis
  • patellar tendonitis
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

DBLOH_HUMAN
  • Deafness, autosomal dominant, 64 (DFNA64) [MIM:614152]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269 PubMed:21722859}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for DIABLO

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 DIABLO: view

No data available for Genatlas for DIABLO Gene

Publications for DIABLO Gene

  1. Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64. (PMID: 21722859) Cheng J … Yuan H (American journal of human genetics 2011) 2 3 4 56
  2. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. (PMID: 14523016) Fu J … Arend LJ (The Journal of biological chemistry 2003) 3 4 23 56
  3. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. (PMID: 10929711) Du C … Wang X (Cell 2000) 3 4 23 56
  4. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. (PMID: 11140637) Liu Z … Fesik SW (Nature 2000) 3 4 23 56
  5. Survivin monomer plays an essential role in apoptosis regulation. (PMID: 21536684) Pavlyukov MS … Shakhparonov MI (The Journal of biological chemistry 2011) 3 4 56

Products for DIABLO Gene

Sources for DIABLO Gene