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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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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

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