The succinate dehydrogenase (SDH) complex (or complex II) of the mitochondrial respiratory chain is composed of 4 individual subunits. The protein encoded by this gene resides in the mitochondria, and is essential for SDH assembly, but does not physically associate with the complex in vivo. Mutations in this gene are associated with SDH-defective infantile leukoencephalopathy (... See more...

Aliases for SDHAF1 Gene

Aliases for SDHAF1 Gene

  • Succinate Dehydrogenase Complex Assembly Factor 1 2 3 5
  • Succinate Dehydrogenase Assembly Factor 1, Mitochondrial 3 4
  • LYR Motif-Containing Protein 8 3 4
  • LYR Motif Containing 8 2 3
  • SDH Assembly Factor 1 3 4
  • LYRM8 3 4

External Ids for SDHAF1 Gene

Previous GeneCards Identifiers for SDHAF1 Gene

  • GC19P041178
  • GC19P036486
  • GC19P032991

Summaries for SDHAF1 Gene

Entrez Gene Summary for SDHAF1 Gene

  • The succinate dehydrogenase (SDH) complex (or complex II) of the mitochondrial respiratory chain is composed of 4 individual subunits. The protein encoded by this gene resides in the mitochondria, and is essential for SDH assembly, but does not physically associate with the complex in vivo. Mutations in this gene are associated with SDH-defective infantile leukoencephalopathy (mitochondrial complex II deficiency).[provided by RefSeq, Mar 2010]

GeneCards Summary for SDHAF1 Gene

SDHAF1 (Succinate Dehydrogenase Complex Assembly Factor 1) is a Protein Coding gene. Diseases associated with SDHAF1 include Mitochondrial Complex Ii Deficiency and Kearns-Sayre Syndrome.

UniProtKB/Swiss-Prot Summary for SDHAF1 Gene

  • Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol (PubMed:24954417, PubMed:19465911). Promotes maturation of the iron-sulfur protein subunit SDHB of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants (PubMed:24954417). May act together with SDHAF3 (PubMed:24954417). Contributes to iron-sulfur cluster incorporation into SDHB by binding to SDHB and recruiting the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241).

Additional gene information for SDHAF1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SDHAF1 Gene

Genomics for SDHAF1 Gene

GeneHancer (GH) Regulatory Elements for SDHAF1 Gene

Promoters and enhancers for SDHAF1 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
GH19J035994 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 500.7 +0.4 413 3.2 EP300 ZBTB40 ZNF217 SIN3A NRF1 TCF12 POLR2G SP1 RBAK PHF8 SDHAF1 ZNF566 ZNF568 ZNF529 ZNF461 ZNF790-AS1 ZFP82 ZNF345 ZNF567 ZNF260
GH19J035993 Enhancer 0.6 Ensembl ENCODE 500.7 -2.0 -1963 0.8 RELA IKZF1 SPI1 ZNF121 PKNOX1 SDHAF1 WDR62 piR-56580-016
GH19J036666 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 20.8 +671.7 671713 3.8 ZBTB40 ZNF217 EP300 ZSCAN5C SIN3A NRF1 TCF12 POLR2G SP1 RBAK ZNF567 ZNF461 ENSG00000276071 lnc-ZNF461-2 ZNF527 ZNF260 ZNF585B ZNF566 LINC01534 ZNF790
GH19J036213 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas 18 +220.5 220462 4.3 ZBTB40 ZNF217 SIN3A NRF1 MYC TCF12 POLR2G USF1 SP1 NCOR1 ZNF146 ZNF565 lnc-COX7A1-4 ZNF345 ZNF567 TMEM147-AS1 ZNF850 ZNF790 HAUS5 ZNF529
GH19J035031 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 18 -964.5 -964472 2.2 NRF1 ZNF300 POLR2G ZNF639 ZBTB5 ZIC2 ZBTB10 ZBTB11 ZNF423 ZNF623 SCN1B lnc-ZNF792-9 LSM14A TMEM147-AS1 HAUS5 KIAA0355 ZNF599 RBM42 PROSER3 KMT2B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SDHAF1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SDHAF1

Genomic Locations for SDHAF1 Gene

Genomic Locations for SDHAF1 Gene
chr19:35,995,188-35,996,318
(GRCh38/hg38)
Size:
1,131 bases
Orientation:
Plus strand
chr19:36,486,090-36,487,220
(GRCh37/hg19)
Size:
1,131 bases
Orientation:
Plus strand

Genomic View for SDHAF1 Gene

Genes around SDHAF1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SDHAF1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SDHAF1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SDHAF1 Gene

Proteins for SDHAF1 Gene

  • Protein details for SDHAF1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    A6NFY7-SDHF1_HUMAN
    Recommended name:
    Succinate dehydrogenase assembly factor 1, mitochondrial
    Protein Accession:
    A6NFY7
    Secondary Accessions:
    • B2RPM7

    Protein attributes for SDHAF1 Gene

    Size:
    115 amino acids
    Molecular mass:
    12806 Da
    Quaternary structure:
    • Interacts with SDHB within an SDHA-SDHB subcomplex (PubMed:19465911, PubMed:26749241). Also interacts with the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241). Binding of SDHAF1 to SDHB precedes and is necessary for recruitment of the iron-sulfur transfer complex by SDHAF1 (PubMed:26749241).
    Miscellaneous:
    • Riboflavin supplementation, which is used as a treatment in SDHAF1-deficient patients, enhances SDHA flavinylation and activity and reduces levels of HIF1A, HIF2A and succinate.

neXtProt entry for SDHAF1 Gene

Post-translational modifications for SDHAF1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SDHAF1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SDHAF1 Gene

Domains & Families for SDHAF1 Gene

Gene Families for SDHAF1 Gene

Protein Domains for SDHAF1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SDHAF1 Gene

GenScript: Design optimal peptide antigens:
  • LYR motif-containing protein 8 (SDHF1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

A6NFY7

UniProtKB/Swiss-Prot:

SDHF1_HUMAN :
  • Belongs to the complex I LYR family. SDHAF1 subfamily.
Family:
  • Belongs to the complex I LYR family. SDHAF1 subfamily.
genes like me logo Genes that share domains with SDHAF1: view

Function for SDHAF1 Gene

Molecular function for SDHAF1 Gene

UniProtKB/Swiss-Prot Function:
Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol (PubMed:24954417, PubMed:19465911). Promotes maturation of the iron-sulfur protein subunit SDHB of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants (PubMed:24954417). May act together with SDHAF3 (PubMed:24954417). Contributes to iron-sulfur cluster incorporation into SDHB by binding to SDHB and recruiting the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241).

Phenotypes From GWAS Catalog for SDHAF1 Gene

Gene Ontology (GO) - Molecular Function for SDHAF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 24606901
genes like me logo Genes that share ontologies with SDHAF1: view
genes like me logo Genes that share phenotypes with SDHAF1: view

Human Phenotype Ontology for SDHAF1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SDHAF1 Gene

MGI Knock Outs for SDHAF1:
  • Sdhaf1 Sdhaf1<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SDHAF1 Gene

Localization for SDHAF1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SDHAF1 Gene

Mitochondrion matrix.

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 SDHAF1 gene
Compartment Confidence
mitochondrion 5
nucleus 2
peroxisome 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SDHAF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IEA 19465911
GO:0005759 mitochondrial matrix IEA --
genes like me logo Genes that share ontologies with SDHAF1: view

Pathways & Interactions for SDHAF1 Gene

PathCards logo

SuperPathways for SDHAF1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SDHAF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0034553 mitochondrial respiratory chain complex II assembly IMP 19465911
genes like me logo Genes that share ontologies with SDHAF1: view

No data available for Pathways by source and SIGNOR curated interactions for SDHAF1 Gene

Drugs & Compounds for SDHAF1 Gene

No Compound Related Data Available

Transcripts for SDHAF1 Gene

mRNA/cDNA for SDHAF1 Gene

1 REFSEQ mRNAs :
7 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 SDHAF1 Gene

No ASD Table

Relevant External Links for SDHAF1 Gene

GeneLoc Exon Structure for
SDHAF1

Expression for SDHAF1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SDHAF1 Gene

Protein differential expression in normal tissues from HIPED for SDHAF1 Gene

This gene is overexpressed in Liver (22.0), Frontal cortex (17.6), Testis (13.2), and Fetal Brain (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SDHAF1 Gene



Protein tissue co-expression partners for SDHAF1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SDHAF1

SOURCE GeneReport for Unigene cluster for SDHAF1 Gene:

Hs.356460

mRNA Expression by UniProt/SwissProt for SDHAF1 Gene:

A6NFY7-SDHF1_HUMAN
Tissue specificity: Ubiquitously expressed.

Evidence on tissue expression from TISSUES for SDHAF1 Gene

  • Nervous system(4.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SDHAF1 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
Thorax:
  • heart
  • heart valve
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with SDHAF1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for SDHAF1 Gene

Orthologs for SDHAF1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SDHAF1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SDHAF1 31 30
  • 98.55 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SDHAF1 30
  • 85.22 (n)
-- 31
  • 81 (a)
OneToMany
-- 31
  • 71 (a)
OneToMany
cow
(Bos Taurus)
Mammalia SDHAF1 31 30
  • 83.48 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Sdhaf1 17 31 30
  • 80.58 (n)
oppossum
(Monodelphis domestica)
Mammalia SDHAF1 31
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC101732873 30
  • 55.69 (n)
zebrafish
(Danio rerio)
Actinopterygii sdhaf1 31 30
  • 56.44 (n)
OneToOne
Species where no ortholog for SDHAF1 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • 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 SDHAF1 Gene

ENSEMBL:
Gene Tree for SDHAF1 (if available)
TreeFam:
Gene Tree for SDHAF1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SDHAF1: view image

Paralogs for SDHAF1 Gene

No data available for Paralogs for SDHAF1 Gene

Variants for SDHAF1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SDHAF1 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
691614 Uncertain Significance: Mitochondrial complex II deficiency 35,995,303(+) A/C MISSENSE_VARIANT
rs1085307492 Likely Pathogenic: not provided 35,995,296(+) C/T NONSENSE
rs115204084 Likely Benign: Mitochondrial complex II deficiency 35,995,778(+) G/T THREE_PRIME_UTR_VARIANT
rs1348216250 Likely Benign: not provided 35,995,595(+) A/C SYNONYMOUS_VARIANT
rs137853192 Pathogenic: Mitochondrial complex II deficiency. Mitochondrial complex II deficiency (MT-C2D) [MIM:252011] 35,995,443(+) G/Cp.Gly57Arg MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for SDHAF1 Gene

Structural Variations from Database of Genomic Variants (DGV) for SDHAF1 Gene

Variant ID Type Subtype PubMed ID
dgv51n68 CNV loss 17160897

Variation tolerance for SDHAF1 Gene

Gene Damage Index Score: 0.48; 10.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SDHAF1 Gene

Human Gene Mutation Database (HGMD)
SDHAF1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SDHAF1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SDHAF1 Gene

Disorders for SDHAF1 Gene

MalaCards: The human disease database

(9) MalaCards diseases for SDHAF1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
mitochondrial complex ii deficiency
  • succinate coq reductase deficiency
kearns-sayre syndrome
  • kss
spastic quadriplegia
  • quadriplegic infantile cerebral palsy
leigh syndrome
  • ls
quadriplegia
  • tetraplegia
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

SDHF1_HUMAN
  • Mitochondrial complex II deficiency (MT-C2D) [MIM:252011]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. {ECO:0000269 PubMed:19465911, ECO:0000269 PubMed:22995659, ECO:0000269 PubMed:26749241}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SDHAF1

genes like me logo Genes that share disorders with SDHAF1: view

No data available for Genatlas for SDHAF1 Gene

Publications for SDHAF1 Gene

  1. SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. (PMID: 19465911) Ghezzi D … Zeviani M (Nature genetics 2009) 2 3 4 54
  2. Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to SDHB. (PMID: 26749241) Maio N … Rouault TA (Cell metabolism 2016) 3 4 54
  3. Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency. (PMID: 22995659) Ohlenbusch A … Brockmann K (Orphanet journal of rare diseases 2012) 3 4 54
  4. A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III. (PMID: 28380382) Maio N … Rouault TA (Cell metabolism 2017) 3 54
  5. N-terminome analysis of the human mitochondrial proteome. (PMID: 25944712) Vaca Jacome AS … Carapito C (Proteomics 2015) 4 54

Products for SDHAF1 Gene

Sources for SDHAF1 Gene