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

Summary

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: mouse all
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Genomic context

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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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	Compare labs

EBI GWAS Catalog

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

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G20545 (e-PCR)
- UniSTS:39190

A005W03 (e-PCR)
- UniSTS:39191

D11S3374 (e-PCR)
- UniSTS:152616

SHGC-108146 (e-PCR)
- UniSTS:170581

D13S1553 (e-PCR)
- UniSTS:473482

RH12460 (e-PCR)
- UniSTS:669

D6S1789 (e-PCR)
- UniSTS:61860

SHGC-57597 (e-PCR)
- UniSTS:13477

AL035373 (e-PCR)
- UniSTS:95175

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 more info	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

NG_051651.2 RefSeqGene

Range

5000..157531

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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

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
NR_104418.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AF170070, AL035653, BC067762, CA310019, HY168919

Related

ENST00000468929.5
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