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    LHX4 LIM homeobox 4 [ Homo sapiens (human) ]

    Gene ID: 89884, updated on 27-Nov-2024

    Summary

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    Official Symbol
    LHX4provided by HGNC
    Official Full Name
    LIM homeobox 4provided by HGNC
    Primary source
    HGNC:HGNC:21734
    See related
    Ensembl:ENSG00000121454 MIM:602146; AllianceGenome:HGNC:21734
    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
    CPHD4
    Summary
    This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor involved in the control of differentiation and development of the pituitary gland. Mutations in this gene cause combined pituitary hormone deficiency 4. [provided by RefSeq, Dec 2010]
    Expression
    Ubiquitous expression in testis (RPKM 1.2), placenta (RPKM 0.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See LHX4 in Genome Data Viewer
    Location:
    1q25.2
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (180228375..180278984)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (179583799..179634371)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (180199399..180248119)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371636 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1592 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2159 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180134845-180135502 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180135503-180136160 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180136161-180136816 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180136817-180137474 Neighboring gene quiescin sulfhydryl oxidase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2160 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:180162034-180162705 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_1382 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_1383 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1593 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180213501-180214248 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:180217481-180217981 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:180218267-180219247 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180223097-180223616 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:180227074-180227843 Neighboring gene Sharpr-MPRA regulatory region 8966 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:180240649-180241576 Neighboring gene LHX4 antisense RNA 1 Neighboring gene acyl-CoA binding domain containing 6 Neighboring gene MPRA-validated peak481 silencer Neighboring gene MPRA-validated peak482 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:180295724-180296224 Neighboring gene MPRA-validated peak483 silencer Neighboring gene MPRA-validated peak484 silencer Neighboring gene uncharacterized LOC124904702 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2161 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2162 Neighboring gene uncharacterized LOC105371637

    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
    • 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. A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined pituitary hormone deficiency. Tajima T, et al. Exp Clin Endocrinol Diabetes, 2010 Jul. PMID 19856252
    2. Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism. Takagi M, et al. PLoS One, 2012. PMID 23029363, Free PMC Article
    3. Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4. Filges I, et al. Pediatrics, 2012 Feb. PMID 22232309
    4. Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation. Gregory LC, et al. J Clin Endocrinol Metab, 2015 Jun. PMID 25871839, Free PMC Article
    5. Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue. Rochette C, et al. PLoS One, 2015. PMID 25955177, Free PMC Article

    See all (44) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.
      Title: Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.
    2. LHX4 Mutation is associated with Pituitary Deficits.
      Title: Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients.
    3. The study identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R.
      Title: Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue.
    4. A novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life.
      Title: Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation.
    5. we found that LHX4 upregulated beta-catenin levels in human colorectal cancer cell lines
      Title: Oncogenicity of LHX4 in colorectal cancer through Wnt/β-catenin/TCF4 cascade.
    6. Data indicate that HESX1, LHX4 and SOX3 polymorphisms may be associated with pituitary stalk interruption syndrome (PSIS).
      Title: Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis.
    7. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation.
      Title: Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism.
    8. Variably penetrant pituitary insufficiency, including this severe and atypical presentation, can be correlated with LHX4 insufficiency and highlights the role of LHX4 for pituitary development.
      Title: Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4.
    9. data indicate that LHX4 may act as a potential tumor suppressor in hepatocarcinogenesis, suggesting that targeting LHX4 to downregulate AFP might have therapeutic implications
      Title: Downregulation of alpha-fetoprotein expression by LHX4: a critical role in hepatocarcinogenesis.
    10. A novel HESX1 causative mutation was found in a consanguineous family, and two LHX4 mutations were present in familial Pituitary stalk interruption syndrome.
      Title: Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    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
    Short stature-pituitary and cerebellar defects-small sella turcica syndrome
    MedGen: C2678408 OMIM: 262700 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2022-04-25)

    ClinGen Genome Curation Page
    Haploinsufficency

    Little evidence for dosage pathogenicity (Last evaluated 2022-04-25)

    ClinGen Genome Curation PagePubMed

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Clone Names

    • FLJ22769

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables methyl-CpG binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in animal organ morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in medial motor column neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in motor neuron axon guidance IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in placenta development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    LIM/homeobox protein Lhx4
    Names
    LIM homeobox protein 4

    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_008081.1 RefSeqGene

      Range
      4992..49747
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_033343.4 → NP_203129.1  LIM/homeobox protein Lhx4

      Status: REVIEWED

      Source sequence(s)
      AF179849, AL139141, BC011759, BX954266
      Consensus CDS
      CCDS1338.1
      UniProtKB/Swiss-Prot
      Q8NHE0, Q8NHM1, Q8TCJ1, Q8WWX2, Q969G2, Q969W2
      UniProtKB/TrEMBL
      A0A0S2Z5S4
      Related
      ENSP00000263726.2, ENST00000263726.4
      Conserved Domains (3) summary
      cd09376
      Location:89 → 144
      LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family
      cd09468
      Location:30 → 81
      LIM1_Lhx4; The first LIM domain of Lhx4
      pfam00046
      Location:160 → 214
      Homeobox; Homeobox domain

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      180228375..180278984
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011510105.3 → XP_011508407.1  LIM/homeobox protein Lhx4 isoform X1

      Conserved Domains (3) summary
      cd09376
      Location:28 → 83
      LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family
      pfam00046
      Location:99 → 152
      Homeobox; Homeobox domain
      cl02475
      Location:1 → 20
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    2. XM_011510106.4 → XP_011508408.1  LIM/homeobox protein Lhx4 isoform X1

      Conserved Domains (3) summary
      cd09376
      Location:28 → 83
      LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family
      pfam00046
      Location:99 → 152
      Homeobox; Homeobox domain
      cl02475
      Location:1 → 20
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    3. XM_011510108.3 → XP_011508410.1  LIM/homeobox protein Lhx4 isoform X2

      Conserved Domains (2) summary
      cd09376
      Location:14 → 69
      LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family
      pfam00046
      Location:85 → 138
      Homeobox; Homeobox domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      179583799..179634371
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339483.1 → XP_054195458.1  LIM/homeobox protein Lhx4 isoform X1

    2. XM_054339484.1 → XP_054195459.1  LIM/homeobox protein Lhx4 isoform X1

    3. XM_054339485.1 → XP_054195460.1  LIM/homeobox protein Lhx4 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q969G2.2 GenPept UniProtKB/Swiss-Prot:Q969G2

    Gene LinkOut

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

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