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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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LSS
lanosterol synthase
Chromosome 21 Β· 21q22.3
NCBI Gene: 4047Ensembl: ENSG00000160285.16HGNC: HGNC:6708UniProt: B2R694
80PubMed Papers
23Diseases
0Drugs
36Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
steroid biosynthetic processcholesterol biosynthetic processlipid dropletprotein bindingAlopecia-intellectual disability syndromeTotal congenital cataractcataract 44hypotrichosis 14
✦AI Summary

LSS (lanosterol synthase) is a key enzyme in cholesterol biosynthesis that catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, forming the sterol nucleus 1. This amphipathic molecule lanosterol is enriched in the lens and plays a crucial role in preventing protein aggregation and maintaining lens transparency 1. The mechanism involves lanosterol's ability to prevent disruption of crystallin protein interactions, thereby maintaining the highly ordered macro-structure essential for lens function 1. LSS mutations have significant disease relevance, as homozygous missense mutations (W581R and G588S) in LSS cause congenital cataracts by impairing the enzyme's catalytic function 1. Additionally, LSS variants are associated with hypotrichosis 14, a form of congenital alopecia, with novel variants recently identified in Chinese families including deletions and missense mutations 2. The gene is also linked to alopecia-intellectual disability syndrome 4 (APMR4), with patients showing variable degrees of intellectual disability, alopecia, and additional phenotypic features 3. Clinically, lanosterol treatment has shown promise in reducing protein aggregates in vitro and decreasing cataract severity in animal models, suggesting potential therapeutic applications for cataract prevention and treatment 1.

Sources cited
1
LSS catalyzes cyclization of oxidosqualene to lanosterol and lanosterol prevents lens protein aggregation
PMID: 26200341
2
Homozygous LSS mutations W581R and G588S cause congenital cataracts
PMID: 26200341
3
Lanosterol treatment reduces cataract severity in animal models
PMID: 26200341
4
Novel LSS variants cause hypotrichosis 14 in Chinese families
PMID: 40696433
5
LSS mutations cause alopecia-intellectual disability syndrome 4 with variable phenotypes
PMID: 36251212
Disease Associationsβ“˜23
Alopecia-intellectual disability syndromeOpen Targets
0.73Strong
Total congenital cataractOpen Targets
0.69Moderate
cataract 44Open Targets
0.67Moderate
hypotrichosis 14Open Targets
0.63Moderate
hypotrichosisOpen Targets
0.60Moderate
neurodegenerative diseaseOpen Targets
0.54Moderate
genetic disorderOpen Targets
0.45Moderate
alopeciaOpen Targets
0.42Moderate
Intellectual disabilityOpen Targets
0.42Moderate
Global developmental delayOpen Targets
0.42Moderate
Abnormality of the genital systemOpen Targets
0.42Moderate
Abnormality of the skinOpen Targets
0.42Moderate
HypotoniaOpen Targets
0.42Moderate
microcephalyOpen Targets
0.42Moderate
SeizureOpen Targets
0.42Moderate
cataractOpen Targets
0.39Weak
hypotrichosis simplexOpen Targets
0.37Weak
autosomal recessive palmoplantar keratoderma and congenital alopeciaOpen Targets
0.37Weak
alopecia - intellectual disability syndromeOpen Targets
0.37Weak
total early-onset cataractOpen Targets
0.37Weak
Alopecia-intellectual disability syndrome 4UniProt
Cataract 44UniProt
Hypotrichosis 14UniProt
Pathogenic Variants36
NM_002340.6(LSS):c.530G>A (p.Arg177Gln)Pathogenic
not provided|Alopecia-intellectual disability syndrome 4;Cataract 44;Hypotrichosis 14
β˜…β˜…β˜†β˜†2024β†’ Residue 177
NM_002340.6(LSS):c.857A>G (p.Tyr286Cys)Likely pathogenic
Hypotrichosis 14|Alopecia-intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 286
NM_002340.6(LSS):c.647G>A (p.Trp216Ter)Pathogenic
Hypotrichosis 14|Alopecia-intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 216
NM_002340.6(LSS):c.676_685dup (p.Leu229fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 229
NM_002340.6(LSS):c.775del (p.Leu259fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 259
NM_002340.6(LSS):c.1670+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_002340.6(LSS):c.1172T>C (p.Phe391Ser)Likely pathogenic
Hypotrichosis 14|Cataract 44
β˜…β˜†β˜†β˜†2025β†’ Residue 391
NM_002340.6(LSS):c.443del (p.Lys148fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 148
NM_002340.6(LSS):c.625A>T (p.Asn209Tyr)Likely pathogenic
Alopecia-intellectual disability syndrome 4|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 209
NM_002340.6(LSS):c.523C>T (p.Arg175Ter)Likely pathogenic
Alopecia-intellectual disability syndrome 4
β˜…β˜†β˜†β˜†2024β†’ Residue 175
NM_002340.6(LSS):c.1317+1G>TLikely pathogenic
Cataract 44
β˜…β˜†β˜†β˜†2024
NM_002340.6(LSS):c.1021del (p.Thr341fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 341
NM_002340.6(LSS):c.1989-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_002340.6(LSS):c.1702C>T (p.Arg568Trp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 568
NM_002340.6(LSS):c.1565-2delLikely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024
NM_002340.6(LSS):c.3G>C (p.Met1Ile)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 1
NM_002340.6(LSS):c.1810C>T (p.Arg604Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 604
NM_002340.6(LSS):c.626A>T (p.Asn209Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 209
NM_002340.6(LSS):c.1547A>G (p.Asn516Ser)Likely pathogenic
Alopecia-intellectual disability syndrome 4|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 516
NM_002340.6(LSS):c.1016C>T (p.Ser339Leu)Pathogenic
Alopecia-intellectual disability syndrome 4
β˜…β˜†β˜†β˜†2023β†’ Residue 339
View on ClinVar β†—
Related Genes
ACAT2Protein interaction100%CYP7A1Protein interaction100%HMGCS2Protein interaction100%HSD3B1Protein interaction100%HSD3B2Protein interaction100%ERG28Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Ovary
84%
Lung
65%
Heart
48%
Brain
39%
Bone Marrow
22%
Gene Interaction Network
Click a node to explore
LSSACAT2CYP7A1HMGCS2HSD3B1HSD3B2ERG28
PROTEIN STRUCTURE
Preparing viewer…
PDB1W6K Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.05LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.88 [0.74–1.05]
RankingsWhere LSS stands among ~20K protein-coding genes
  • #5,938of 20,598
    Most Researched80
  • #1,650of 5,498
    Most Pathogenic Variants36
  • #10,503of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedLSS
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Lumbar spinal stenosis.
PMID: 20227646
Best Pract Res Clin Rheumatol Β· 2010
1.00
2
Lanosterol reverses protein aggregation in cataracts.
PMID: 26200341
Nature Β· 2015
0.90
3
A Review of Lumbar Spinal Stenosis with Intermittent Neurogenic Claudication: Disease and Diagnosis.
PMID: 31808530
Pain Med Β· 2019
0.80
4
Low shear stress exacerbates atherosclerosis by inducing the generation of neutrophil extracellular traps via Piezo1-mediated mechanosensation.
PMID: 38412763
Atherosclerosis Β· 2024
0.70
5
Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review.
PMID: 40696433
Hum Genomics Β· 2025
0.60