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    LSS lanosterol synthase [ Homo sapiens (human) ]

    Gene ID: 4047, updated on 5-Mar-2024

    Summary

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    Official Symbol
    LSSprovided by HGNC
    Official Full Name
    lanosterol synthaseprovided by HGNC
    Primary source
    HGNC:HGNC:6708
    See related
    Ensembl:ENSG00000160285 MIM:600909; AllianceGenome:HGNC:6708
    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
    OSC; APMR4; HYPT14; CTRCT44
    Summary
    The protein encoded by this gene catalyzes the conversion of (S)-2,3 oxidosqualene to lanosterol. The encoded protein is a member of the terpene cyclase/mutase family and catalyzes the first step in the biosynthesis of cholesterol, steroid hormones, and vitamin D. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2009]
    Expression
    Ubiquitous expression in skin (RPKM 17.0), lung (RPKM 14.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    21q22.3
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (46188446..46228774, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (44570708..44611332, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (47608360..47648688, complement)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47571745-47572448 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47572449-47573154 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47573155-47573858 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47573859-47574562 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47574563-47575266 Neighboring gene formimidoyltransferase cyclodeaminase Neighboring gene FTCD antisense RNA 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:47590104-47590604 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:47590605-47591105 Neighboring gene spermatogenesis and centriole associated 1 like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47600015-47600618 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47602435-47603038 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47603039-47603642 Neighboring gene uncharacterized LOC124905045 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47611464-47612078 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47612079-47612691 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47614165-47614666 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47614667-47615166 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:47621241-47621767 Neighboring gene small nucleolar RNA, C/D box 159 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47638552-47639452 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47640419-47640920 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18598 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13413 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13414 Neighboring gene Sharpr-MPRA regulatory region 3947 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13416 Neighboring gene MCM3AP antisense RNA 1 Neighboring gene minichromosome maintenance complex component 3 associated protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18599 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13417 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13418 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:47709143-47709725 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:47709726-47710307 Neighboring gene Sharpr-MPRA regulatory region 4411 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:47715289-47715862 Neighboring gene Sharpr-MPRA regulatory region 1466 Neighboring gene ybeY metalloendoribonuclease Neighboring gene chromosome 21 open reading frame 58

    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. Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes. Cesarato N, et al. Am J Med Genet A, 2021 Dec. PMID 34318586
    2. Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene. Hua S, et al. J Dermatol, 2021 Mar. PMID 33222230
    3. A novel and a known mutation in LSS gene associated with hypotrichosis 14 in a Chinese family. Li F, et al. J Dermatol, 2019 Nov. PMID 31322293
    4. Target identification reveals lanosterol synthase as a vulnerability in glioma. Phillips RE, et al. Proc Natl Acad Sci U S A, 2019 Apr 16. PMID 30923116, Free PMC Article
    5. Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome. Besnard T, et al. Genet Med, 2019 Sep. PMID 30723320

    See all (69) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LSS rs2254524 Increases the Risk of Hypertension in Children and Adolescents with Obesity.
      Title: LSS rs2254524 Increases the Risk of Hypertension in Children and Adolescents with Obesity.
    2. Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes.
      Title: Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes.
    3. Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene.
      Title: Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene.
    4. The Polymorphism rs2968 of LSS Gene Confers Susceptibility to Age-Related Cataract.
      Title: The Polymorphism rs2968 of LSS Gene Confers Susceptibility to Age-Related Cataract.
    5. Study describes identification of novel mutation 1885T>A (p.Trp629Arg) in the LSS gene in the squalene cyclase, C-terminal domain associated with hypotrichosis 14 in a Chinese family.
      Title: A novel and a known mutation in LSS gene associated with hypotrichosis 14 in a Chinese family.
    6. Study identified two patients with novel biallelic LSS mutations who exhibited congenital hypotrichosis and midline anomalies but did not have cataracts. Epidermis-specific Lss knockout mice showed neonatal lethality due to dehydration, indicating that LSS could be involved in skin barrier integrity. Knockout of Lss in the epidermis caused hypotrichosis in adult mice. Lens-specific Lss knockout mice had cataracts.
      Title: Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice.
    7. Investigated lanosterol synthase as a possible target for treatment of glioma.
      Title: Target identification reveals lanosterol synthase as a vulnerability in glioma.
    8. In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.
      Title: Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome.
    9. LSS gene mutation is associated with Congenital cataract.
      Title: Congenital cataract with LSS gene mutations: a new case report.
    10. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet.
      Title: Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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
    Alopecia-intellectual disability syndrome 4
    MedGen: C5394241 OMIM: 618840 GeneReviews: Not available
    		Compare labs
    Cataract 44
    MedGen: C4225300 OMIM: 616509 GeneReviews: Not available
    		Compare labs
    Hypotrichosis 14
    MedGen: C4748930 OMIM: 618275 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2012-09-06)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2012-09-06)

    ClinGen Genome Curation Page

    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

    Clone Names

    • FLJ25486, FLJ35015, FLJ39450, FLJ46393

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables lanosterol synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables lanosterol synthase activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables lanosterol synthase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables lanosterol synthase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cholesterol biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cholesterol biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cholesterol biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of protein stability IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in steroid biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in triterpenoid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in lipid droplet IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lipid droplet IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 

    General protein information

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    Preferred Names
    lanosterol synthase
    Names
    2,3-epoxysqualene-lanosterol cyclase
    epididymis secretory sperm binding protein
    hOSC
    lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)
    oxidosqualene--lanosterol cyclase
    NP_001001438.1
    NP_001138908.1
    NP_001138909.1
    NP_002331.3

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_011510.1 RefSeqGene

      Range
      5051..45379
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001001438.3 → NP_001001438.1  lanosterol synthase isoform 1

      See identical proteins and their annotated locations for NP_001001438.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the shortest transcript. Variants 1 and 2 encode the same protein (isoform 1).
      Source sequence(s)
      AK312489, D63807
      Consensus CDS
      CCDS13733.1
      UniProtKB/Swiss-Prot
      B4DJZ9, D3DSN0, E9PEI9, G5E9Q9, P48449, Q8IYL6, Q9UEZ1
      UniProtKB/TrEMBL
      A0A384MTQ5
      Related
      ENSP00000348762.3, ENST00000356396.8
      Conserved Domains (1) summary
      TIGR01787
      Location:76 → 721
      squalene_cyclas; squalene/oxidosqualene cyclases

    2. NM_001145436.2 → NP_001138908.1  lanosterol synthase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region and has a different 3' UTR, compared to variant 2. These differences result in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AK296313, AP001468, D63807
      Consensus CDS
      CCDS46654.1
      UniProtKB/TrEMBL
      A0A384MTQ5
      Related
      ENSP00000429133.1, ENST00000522411.5
      Conserved Domains (1) summary
      TIGR01787
      Location:76 → 710
      squalene_cyclas; squalene/oxidosqualene cyclases

    3. NM_001145437.2 → NP_001138909.1  lanosterol synthase isoform 3

      See identical proteins and their annotated locations for NP_001138909.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) retains an intron segment between exons 1 and 2, compared to variant 2. This difference introduces a premature stop codon and results in the use of a downstream, in-frame start codon. The encoded protein (isoform 3) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK226141, AP001468, D63807, DA333499
      Consensus CDS
      CCDS54489.1
      UniProtKB/TrEMBL
      A0A384MTQ5
      Related
      ENSP00000409191.2, ENST00000457828.6
      Conserved Domains (2) summary
      cd02892
      Location:1 → 639
      SQCY_1; Squalene cyclase (SQCY) domain subgroup 1; found in class II terpene cyclases that have an alpha 6 - alpha 6 barrel fold. Squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY) are integral membrane proteins that catalyze a cationic cyclization ...
      TIGR01787
      Location:1 → 641
      squalene_cyclas; squalene/oxidosqualene cyclases

    4. NM_002340.6 → NP_002331.3  lanosterol synthase isoform 1

      See identical proteins and their annotated locations for NP_002331.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 3' UTR, compared to variant 2. Variants 1 and 2 encode the same protein (isoform 1).
      Source sequence(s)
      AK312489, AP001468, D63807
      Consensus CDS
      CCDS13733.1
      UniProtKB/Swiss-Prot
      B4DJZ9, D3DSN0, E9PEI9, G5E9Q9, P48449, Q8IYL6, Q9UEZ1
      UniProtKB/TrEMBL
      A0A384MTQ5
      Related
      ENSP00000380837.2, ENST00000397728.8
      Conserved Domains (1) summary
      TIGR01787
      Location:76 → 721
      squalene_cyclas; squalene/oxidosqualene cyclases

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      46188446..46228774 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187626.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      49816..80959 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      44570708..44611332 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P48449.1 GenPept UniProtKB/Swiss-Prot:P48449

    Gene LinkOut

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

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