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LYRM4 LYR motif containing 4 [ Homo sapiens (human) ]

Gene ID: 57128, updated on 2-Nov-2024

Summary

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Official Symbol
LYRM4provided by HGNC
Official Full Name
LYR motif containing 4provided by HGNC
Primary source
HGNC:HGNC:21365
See related
Ensembl:ENSG00000214113 MIM:613311; AllianceGenome:HGNC:21365
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ISD11; CGI-203; COXPD19; C6orf149
Summary
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]
Expression
Ubiquitous expression in ovary (RPKM 2.3), thyroid (RPKM 2.1) and 25 other tissues See more
Orthologs
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Genomic context

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See LYRM4 in Genome Data Viewer
Location:
6p25.1
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (5031753..5260950, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (4900453..5130157, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (5068561..5261183, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16864 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16865 Neighboring gene MPRA-validated peak5630 silencer Neighboring gene uncharacterized LOC124901248 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:5027971-5028470 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:5031032-5031192 Neighboring gene LYRM4 antisense RNA 1 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:5044856-5046055 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23899 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23900 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:5063575-5064076 Neighboring gene ribonuclease P/MRP subunit p40 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16866 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16867 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16868 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16869 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:5085857-5086546 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23901 Neighboring gene MPRA-validated peak5632 silencer Neighboring gene TFB2M pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:5130070-5130656 Neighboring gene protein phosphatase 1 regulatory subunit 3G Neighboring gene Sharpr-MPRA regulatory region 2533 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:5193017-5193524 Neighboring gene microRNA 3691 Neighboring gene Sharpr-MPRA regulatory region 15549 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:5230418-5231617 Neighboring gene uncharacterized LOC124901249 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23902 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16873 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16874 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23903 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16876 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23904 Neighboring gene Sharpr-MPRA regulatory region 4425 Neighboring gene phenylalanyl-tRNA synthetase 2, mitochondrial Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:5368745-5369944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23906 Neighboring gene NANOG hESC enhancer GRCh37_chr6:5412113-5412622 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:5438556-5439472 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:5439473-5440389 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:5456946-5457932 Neighboring gene FARS2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23907 Neighboring gene MPRA-validated peak5636 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23908 Neighboring gene NANOG hESC enhancer GRCh37_chr6:5529614-5530223 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:5541695-5542894 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:5581546-5582745 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 37

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis. Shi Y, et al. Hum Mol Genet, 2009 Aug 15. PMID 19454487, Free PMC Article
  2. The Eukaryotic-Specific ISD11 Is a Complex-Orphan Protein with Ability to Bind the Prokaryotic IscS. Yan R, et al. PLoS One, 2016. PMID 27427956, Free PMC Article
  3. Promoter polymorphisms in two overlapping 6p25 genes implicate mitochondrial proteins in cognitive deficit in schizophrenia. Jablensky A, et al. Mol Psychiatry, 2012 Dec. PMID 21968932
  4. Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability: IMPLICATIONS IN THE DEVELOPMENT OF MITOCHONDRIAL DISORDER, COXPD19. Saha PP, et al. J Biol Chem, 2015 Oct 23. PMID 26342079, Free PMC Article
  5. Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. Cory SA, et al. Proc Natl Acad Sci U S A, 2017 Jul 3. PMID 28634302, Free PMC Article

See all (63) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. In this work, the structure of the human mitochondrial ACP-ISD11 heterodimer was determined at 2.0 A resolution.
    Title: Structure of the Human ACP-ISD11 Heterodimer.
  2. The molecular structure of the human mitochondrial cysteine desulfurase complex consisting of two copies each of NFS1, ISD11, and acyl carrier protein has been described.
    Title: Architectural Features of Human Mitochondrial Cysteine Desulfurase Complexes from Crosslinking Mass Spectrometry and Small-Angle X-Ray Scattering.
  3. analysis of the NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters
    Title: Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.
  4. Human Isd11 (ISD11) is a helical protein which exists in solution as an equilibrium between monomer, dimeric and tetrameric species when in the absence of human Nfs1 (NFS1). Recombinant ISD11 expressed in E. coli co-purifies with the bacterial orthologue of NFS1, IscS.
    Title: The Eukaryotic-Specific ISD11 Is a Complex-Orphan Protein with Ability to Bind the Prokaryotic IscS.
  5. The NFS1/ISD11 complex further interacts with scaffold protein ISCU and regulator protein frataxin, thereby forming a quaternary complex for Fe-S cluster formation.
    Title: The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with l-Cysteine Desulfurase NFS1.
  6. Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN(42-210)]24.[NFS1]24.[ISD11]24.[ISCU]24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components.
    Title: Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery.
  7. Our findings highlight that the ISD11 R68A/R68L mutation display reduced affinity to form a stable subcomplex with NFS1, and thereby fails to prevent NFS1 aggregation resulting in impairment of the Fe-S cluster biogenesis
    Title: Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability: IMPLICATIONS IN THE DEVELOPMENT OF MITOCHONDRIAL DISORDER, COXPD19.
  8. Homozygous mutation in LYRM4 was reported in two patients with combined oxidative phosphorylation deficiency.
    Title: Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes.
  9. LYRM4 downregulation may be one of the mechanisms involved in inefficient oxidative phosphorylation and oxidative stress, increasingly recognised as contributors to schizophrenia pathogenesis.
    Title: Promoter polymorphisms in two overlapping 6p25 genes implicate mitochondrial proteins in cognitive deficit in schizophrenia.
  10. Strong candidate gene for mitochondrial disease, based on recessive mutations detected in infantile patients
    Title: Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.
Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Combined oxidative phosphorylation deficiency 19
MedGen: C3810055 OMIM: 615595 GeneReviews: Not available
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EBI GWAS Catalog

Description
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
EBI GWAS Catalog
Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in [2Fe-2S] cluster assembly IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of [4Fe-4S] cluster assembly ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in iron-sulfur cluster assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in iron-sulfur cluster assembly NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
part_of L-cysteine desulfurase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of iron-sulfur cluster assembly complex NAS
Non-traceable Author Statement
more info
 PubMed 
part_of mitochondrial [2Fe-2S] assembly complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrion NAS
Non-traceable Author Statement
more info
 PubMed 
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
LYR motif-containing protein 4
Names
homolog of yeast Isd11
mitochondrial matrix Nfs1 interacting protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_051651.2 RefSeqGene

    Range
    5000..157531
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001164840.3 → NP_001158312.1  LYR motif-containing protein 4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate 3' coding region and 3' UTR compared to variant 1. The encoded isoform (2) has a distinct, longer C-terminus compared to isoform 1.
    Source sequence(s)
    CK819966, HY168919
    Consensus CDS
    CCDS54962.1
    UniProtKB/TrEMBL
    F5H189
    Related
    ENSP00000443900.3, ENST00000500576.4
    Conserved Domains (2) summary
    pfam13232
    Location:7 → 67
    Complex1_LYR_1; Complex1_LYR-like
    pfam13900
    Location:75 → 122
    GVQW; Putative domain of unknown function

  2. NM_001164841.3 → NP_001158313.1  LYR motif-containing protein 4 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) includes an additional exon that results in an alternate 3' coding region and 3' UTR compared to variant 1. The encoded isoform (3) has a distinct, longer C-terminus compared to isoform 1.
    Source sequence(s)
    AF170070, AL035653, BC067762, BX353584, CA310019, HY168919
    Consensus CDS
    CCDS54961.1
    UniProtKB/TrEMBL
    C9JRX8
    Related
    ENSP00000420026.1, ENST00000464010.5
    Conserved Domains (1) summary
    pfam13232
    Location:7 → 67
    Complex1_LYR_1; Complex1_LYR-like

  3. NM_001318782.1 → NP_001305711.1  LYR motif-containing protein 4 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) contains an alternate 3' coding region and 3' UTR compared to variant 1. The encoded isoform (4) has a distinct, shorter C-terminus compared to isoform 1.
    Source sequence(s)
    AK309661, AL035653, HY168919
    Consensus CDS
    CCDS83061.1
    UniProtKB/TrEMBL
    C9JY28
    Related
    ENSP00000419928.1, ENST00000480566.5
    Conserved Domains (1) summary
    pfam13232
    Location:7 → 67
    Complex1_LYR_1; Complex1_LYR-like

  4. NM_001318783.1 → NP_001305712.1  LYR motif-containing protein 4 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) contains an alternate 3' coding region and 3' UTR compared to variant 1. The encoded isoform (5) has a distinct, longer C-terminus compared to isoform 1.
    Source sequence(s)
    AL121978, DA114665, HY168919
    Conserved Domains (1) summary
    pfam13232
    Location:7 → 67
    Complex1_LYR_1; Complex1_LYR-like

  5. NM_020408.6 → NP_065141.3  LYR motif-containing protein 4 isoform 1

    See identical proteins and their annotated locations for NP_065141.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AF170070, AL035653, BC067762, CA310019, HY168919
    Consensus CDS
    CCDS4493.1
    UniProtKB/Swiss-Prot
    A8K543, Q5XKP1, Q9HD34
    Related
    ENSP00000418787.1, ENST00000330636.9
    Conserved Domains (1) summary
    pfam13232
    Location:7 → 67
    Complex1_LYR_1; Complex1_LYR-like

RNA

  1. NR_104417.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an additional exon in the 3' region compared to variant 1. This variant is represented as non-coding because use of the expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF170070, AK309458, AL035653, BC067762, CA310019, HY168919
    Related
    ENST00000463032.5

  2. NR_104418.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AF170070, AL035653, BC067762, CA310019, HY168919
    Related
    ENST00000468929.5

  3. NR_134856.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) lacks an exon and contains two alternate 3' exons compared to variant 1. This variant is represented as non-coding because use of the expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    DA114665, DA222333, HY168919

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    5031753..5260950 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017011084.3 → XP_016866573.1  LYR motif-containing protein 4 isoform X1

  2. XM_017011083.3 → XP_016866572.1  LYR motif-containing protein 4 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    4900453..5130157 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054355978.1 → XP_054211953.1  LYR motif-containing protein 4 isoform X1

  2. XM_054355979.1 → XP_054211954.1  LYR motif-containing protein 4 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9HD34.1 GenPept UniProtKB/Swiss-Prot:Q9HD34

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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