The protein encoded by this gene is found in both mitochondria and the nucleus, where it binds cysteine desulfurase and helps free inorganic sulfur for Fe/S clusters. Disruption of this gene negatively impacts mitochondrial and cytosolic iron homeostasis. [provided by RefSeq, Sep 2016] See more...

Aliases for LYRM4 Gene

Aliases for LYRM4 Gene

  • LYR Motif Containing 4 2 3 5
  • ISD11 2 3 4
  • LYR Motif-Containing Protein 4 3 4
  • C6orf149 3 4
  • CGI-203 2 3
  • Mitochondrial Matrix Nfs1 Interacting Protein 3
  • Chromosome 6 Open Reading Frame 149 2
  • Homolog Of Yeast Isd11 3
  • COXPD19 3
  • LYRM4 5

External Ids for LYRM4 Gene

Previous HGNC Symbols for LYRM4 Gene

  • C6orf149

Previous GeneCards Identifiers for LYRM4 Gene

  • GC06M005049
  • GC06M005103
  • GC06M004983

Summaries for LYRM4 Gene

Entrez Gene Summary for LYRM4 Gene

  • The protein encoded by this gene is found in both mitochondria and the nucleus, where it binds cysteine desulfurase and helps free inorganic sulfur for Fe/S clusters. Disruption of this gene negatively impacts mitochondrial and cytosolic iron homeostasis. [provided by RefSeq, Sep 2016]

GeneCards Summary for LYRM4 Gene

LYRM4 (LYR Motif Containing 4) is a Protein Coding gene. Diseases associated with LYRM4 include Combined Oxidative Phosphorylation Deficiency 19 and Combined Oxidative Phosphorylation Deficiency. Among its related pathways are Mitochondrial iron-sulfur cluster biogenesis and Metabolism. An important paralog of this gene is HMGA2.

UniProtKB/Swiss-Prot Summary for LYRM4 Gene

  • Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LYRM4 Gene

Genomics for LYRM4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LYRM4 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J005259 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 618 -0.1 -90 3.9 ARHGAP35 SP1 HNRNPL CREB1 TEAD4 PRDM10 TFE3 RFX1 IKZF1 NFKBIZ LYRM4 FARS2 hsa-miR-5096-040 lnc-RPP40-12 CDYL NRN1
GH06J004771 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 18.1 +485.7 485749 7.6 SP1 HNRNPL CREB1 TEAD4 ZNF629 POLR2A ZNF174 BACH1 LARP7 STAT3 CDYL CDYL-AS1 PRPF4B LYRM4 piR-35672-044 RPP40
GH06J005214 Enhancer 1.2 Ensembl ENCODE CraniofacialAtlas 19.5 +45.8 45752 2.8 CTCF RXRB REST RAD21 IRF2 HDAC1 ZNF600 NRF1 MGA CTBP1 LYRM4 FARS2 piR-31534-564 hsa-miR-5096-039 lnc-RPP40-12 PPP1R3G LYRM4-AS1
GH06J005230 Enhancer 1 Ensembl ENCODE 16.9 +29.8 29750 4.4 LEF1 IKZF1 JUND MTA2 PKNOX1 MTA1 ZNF24 DPF2 HDAC1 ETV6 LYRM4 FARS2 piR-31534-564 piR-32287-060 lnc-RPP40-12 PPP1R3G LYRM4-AS1
GH06J005270 Enhancer 1.1 Ensembl ENCODE dbSUPER 11.8 -11.3 -11251 4.8 LEF1 IKZF1 ZNF24 DPF2 HDAC1 SOX6 TCF12 EP300 MGA ARID3A LYRM4 FARS2 piR-33863-054 piR-47820-008 NRN1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LYRM4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LYRM4

Top Transcription factor binding sites by QIAGEN in the LYRM4 gene promoter:
  • Cart-1
  • En-1
  • FOXI1
  • FOXO1
  • FOXO1a
  • HFH-3
  • HOXA3
  • Nkx2-2
  • Pax-4a
  • YY1

Genomic Locations for LYRM4 Gene

Genomic Locations for LYRM4 Gene
229,922 bases
Minus strand
158,346 bases
Minus strand

Genomic View for LYRM4 Gene

Genes around LYRM4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LYRM4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LYRM4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LYRM4 Gene

Proteins for LYRM4 Gene

  • Protein details for LYRM4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    LYR motif-containing protein 4
    Protein Accession:
    Secondary Accessions:
    • A8K543
    • Q5XKP1

    Protein attributes for LYRM4 Gene

    91 amino acids
    Molecular mass:
    10758 Da
    Quaternary structure:
    • Interacts with FXN. Interaction is increased by nickel. Interaction is inhibited by calcium, magnesium, manganese, copper, cobalt, zinc, and iron. Forms a complex with the cytosolic/nuclear form of NFS1. The complex increased the stability of NFS1.
    • Reduction of LYRM4 levels by siRNA increases the total iron content, and reduces cytosolic and mitochondrial aconitase activities and NFS1 protein levels.

    Three dimensional structures from OCA and Proteopedia for LYRM4 Gene

neXtProt entry for LYRM4 Gene

Post-translational modifications for LYRM4 Gene

  • Ubiquitination at Lys58
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for LYRM4 Gene

Domains & Families for LYRM4 Gene

Gene Families for LYRM4 Gene

Protein Domains for LYRM4 Gene

  • Complex 1 LYR protein

Suggested Antigen Peptide Sequences for LYRM4 Gene

GenScript: Design optimal peptide antigens:
  • LYR motif-containing protein 4 (LYRM4_HUMAN)
  • PP3564 (Q8WY88_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the complex I LYR family.
  • Belongs to the complex I LYR family.
genes like me logo Genes that share domains with LYRM4: view

Function for LYRM4 Gene

Molecular function for LYRM4 Gene

UniProtKB/Swiss-Prot Function:
Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.

Phenotypes From GWAS Catalog for LYRM4 Gene

Gene Ontology (GO) - Molecular Function for LYRM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 26342079
genes like me logo Genes that share ontologies with LYRM4: view
genes like me logo Genes that share phenotypes with LYRM4: view

Human Phenotype Ontology for LYRM4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

miRNA for LYRM4 Gene

miRTarBase miRNAs that target LYRM4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LYRM4

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for LYRM4 Gene

Localization for LYRM4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LYRM4 Gene

Mitochondrion. Nucleus.

Subcellular locations from

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 LYRM4 gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 4
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for LYRM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005739 mitochondrion IBA 21873635
GO:0005759 mitochondrial matrix TAS --
GO:0016604 nuclear body IDA --
GO:1990221 L-cysteine desulfurase complex IBA 21873635
genes like me logo Genes that share ontologies with LYRM4: view

Pathways & Interactions for LYRM4 Gene

PathCards logo

SuperPathways for LYRM4 Gene

genes like me logo Genes that share pathways with LYRM4: view

Pathways by source for LYRM4 Gene

2 Reactome pathways for LYRM4 Gene

UniProtKB/Swiss-Prot Q9HD34-LYRM4_HUMAN

  • Pathway: Cofactor biosynthesis; iron-sulfur cluster biosynthesis.

Gene Ontology (GO) - Biological Process for LYRM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016226 iron-sulfur cluster assembly IBA 21873635
GO:0044281 small molecule metabolic process TAS --
genes like me logo Genes that share ontologies with LYRM4: view

No data available for SIGNOR curated interactions for LYRM4 Gene

Drugs & Compounds for LYRM4 Gene

No Compound Related Data Available

Transcripts for LYRM4 Gene

mRNA/cDNA for LYRM4 Gene

22 NCBI additional mRNA sequence :
9 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 LYRM4

Alternative Splicing Database (ASD) splice patterns (SP) for LYRM4 Gene

No ASD Table

Relevant External Links for LYRM4 Gene

GeneLoc Exon Structure for

Expression for LYRM4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LYRM4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for LYRM4 Gene

This gene is overexpressed in Frontal cortex (12.1), Adrenal (9.3), and Gallbladder (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LYRM4 Gene

Protein tissue co-expression partners for LYRM4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LYRM4

SOURCE GeneReport for Unigene cluster for LYRM4 Gene:


mRNA Expression by UniProt/SwissProt for LYRM4 Gene:

Tissue specificity: Reduced mRNA levels in Friedreich ataxia patients.

Evidence on tissue expression from TISSUES for LYRM4 Gene

  • Pancreas(4.2)
  • Heart(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LYRM4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • digestive
  • nervous
  • respiratory
  • skeletal muscle
Head and neck:
  • brain
  • lung
  • liver
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with LYRM4: view

No data available for mRNA differential expression in normal tissues for LYRM4 Gene

Orthologs for LYRM4 Gene

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

Orthologs for LYRM4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia LYRM4 30 31
  • 99.27 (n)
(Mus musculus)
Mammalia Lyrm4 30 17 31
  • 89.38 (n)
(Rattus norvegicus)
Mammalia LOC102550385 30
  • 87.91 (n)
(Canis familiaris)
Mammalia LYRM4 30 31
  • 85.99 (n)
(Bos Taurus)
Mammalia LYRM4 30 31
  • 84.62 (n)
(Gallus gallus)
Aves LYRM4 30 31
  • 75.29 (n)
(Anolis carolinensis)
Reptilia LYRM4 31
  • 65 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lyrm4 30
  • 69.35 (n)
(Danio rerio)
Actinopterygii lyrm4 30 31
  • 60.32 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta bcn92 31
  • 36 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ISD11 31
  • 33 (a)
Species where no ortholog for LYRM4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • 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)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • 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 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 LYRM4 Gene

Gene Tree for LYRM4 (if available)
Gene Tree for LYRM4 (if available)
Evolutionary constrained regions (ECRs) for LYRM4: view image

Paralogs for LYRM4 Gene

Paralogs for LYRM4 Gene Pseudogenes for LYRM4 Gene

genes like me logo Genes that share paralogs with LYRM4: view

Variants for LYRM4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LYRM4 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
676148 Benign: not provided 5,216,777(-) C/T INTRON_VARIANT
676237 Benign: not provided 5,261,059(-) G/A FIVE_PRIME_UTR_VARIANT
676277 Benign: not provided 5,261,030(-) C/T FIVE_PRIME_UTR_VARIANT
676278 Benign: not provided 5,260,903(-) G/A NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
680626 Benign: not provided 5,261,126(-) A/G FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for LYRM4 Gene

Structural Variations from Database of Genomic Variants (DGV) for LYRM4 Gene

Variant ID Type Subtype PubMed ID
dgv10279n54 CNV gain 21841781
dgv10280n54 CNV loss 21841781
dgv5912n100 CNV loss 25217958
dgv5913n100 CNV gain 25217958
esv1673345 CNV deletion 17803354
esv1953097 CNV deletion 18987734
esv2469123 CNV deletion 19546169
esv2660224 CNV deletion 23128226
esv2665378 CNV deletion 23128226
esv2666766 CNV deletion 23128226
esv2731512 CNV deletion 23290073
esv2731513 CNV deletion 23290073
esv28267 CNV gain 19812545
esv29679 CNV loss 19812545
esv3288606 CNV deletion 24192839
esv3302659 CNV tandem duplication 20981092
esv3303097 CNV tandem duplication 20981092
esv3378401 CNV duplication 20981092
esv3567196 CNV deletion 23714750
esv3607964 CNV loss 21293372
esv3607965 CNV loss 21293372
esv3890785 CNV loss 25118596
nsv1017380 CNV gain 25217958
nsv1028185 CNV loss 25217958
nsv462622 CNV gain 19166990
nsv473546 CNV novel sequence insertion 20440878
nsv5179 CNV deletion 18451855
nsv522457 CNV loss 19592680
nsv600871 CNV gain 21841781
nsv600872 CNV gain 21841781
nsv600873 CNV gain 21841781
nsv600878 CNV loss 21841781
nsv600880 CNV loss 21841781
nsv600881 CNV loss 21841781
nsv600882 CNV loss 21841781

Variation tolerance for LYRM4 Gene

Gene Damage Index Score: 11.68; 93.21% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LYRM4 Gene

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

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LYRM4 Gene

Disorders for LYRM4 Gene

MalaCards: The human disease database

(10) MalaCards diseases for LYRM4 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search LYRM4 in MalaCards View complete list of genes associated with diseases


  • Combined oxidative phosphorylation deficiency 19 (COXPD19) [MIM:615595]: A mitochondrial disorder characterized by respiratory distress, hypotonia, and severe lactic acidosis in the newborn period. Other features include gastroesophageal reflux and elevated liver enzymes with normal synthetic function. {ECO:0000269 PubMed:23814038}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for LYRM4

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with LYRM4: view

No data available for Genatlas for LYRM4 Gene

Publications for LYRM4 Gene

  1. Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes. (PMID: 23814038) Lim SC … Compton AG (Human molecular genetics 2013) 2 3 4
  2. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. (PMID: 17331979) Shan Y … Cortopassi G (Human molecular genetics 2007) 3 4 23
  3. Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry. (PMID: 21998595) N'Diaye A … Haiman CA (PLoS genetics 2011) 3 41
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41

Products for LYRM4 Gene

Sources for LYRM4 Gene