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3 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LANCL3
LanC like family member 3
Chromosome X · Xp21.1
NCBI Gene: 347404Ensembl: ENSG00000147036.12HGNC: HGNC:24767UniProt: Q6ZV70
5PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Swiss-Prot Reviewed
carbohydrate metabolic processpeptide modificationautosomal recessive hypophosphatemic ricketspostmenopausal osteoporosisosteoporosismelorheostosis
✦AI Summary

LANCL3 (LanC-like family member 3) is an X-linked gene encoding a protein involved in protein damage repair through glutathione conjugation. While initially hypothesized to participate in lanthionine biosynthesis analogous to bacterial LanC enzymes, LANCL3 does not contribute to lanthionine ketimine production in mammalian brains 1. Instead, LANCL3 functions as part of a family of LanCL proteins that catalyze the addition of glutathione to dehydroamino acids (Dha/Dhb) generated at phosphorylated sites in proteins, driving irreversible C-glutathionylation 2. This mechanism serves as an enzyme-mediated damage repair system that removes reactive electrophilic species from the proteome, particularly those arising from aberrant phosphorylation-induced protein damage 2. Physiologically, LANCL3 appears important for maintaining proteome stability, as LanCL knockout in mice can result in premature death 2. Clinically, LANCL3 has relevance to McLeod syndrome pathogenesis; deletions spanning LANCL3 through the neighboring XK gene cause multi-gene deletion syndromes characterized by neurological and hematological manifestations 3.

Sources cited
1
LANCL proteins are not involved in lanthionine biosynthesis in mammalian brains; LanCL1/2/3 triple knockout mice show normal lanthionine ketimine levels
PMID: 28106097
2
LanCLs catalyze glutathione addition to dehydroamino acids at phosphorylated sites as a protein damage repair mechanism; LanCL knockout in mice can cause premature death
PMID: 33932340
3
LANCL3 deletions spanning exon 2 to XK exon 2 and CYBB exon 3 are associated with McLeod syndrome, a multi-gene deletion syndrome
PMID: 28555782
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
autosomal recessive hypophosphatemic ricketsOpen Targets
0.04Suggestive
osteoporosisOpen Targets
0.04Suggestive
postmenopausal osteoporosisOpen Targets
0.04Suggestive
melorheostosisOpen Targets
0.03Suggestive
hyperostosis corticalis generalisataOpen Targets
0.03Suggestive
pyknoachondrogenesisOpen Targets
0.03Suggestive
medulloblastomaOpen Targets
0.01Suggestive
LeishmaniasisOpen Targets
0.01Suggestive
Crohn's diseaseOpen Targets
0.01Suggestive
primitive neuroectodermal tumorOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
myelodysplastic syndromeOpen Targets
0.00Suggestive
obesityOpen Targets
0.00Suggestive
oligodendrogliomaOpen Targets
0.00Suggestive
osteosarcomaOpen Targets
0.00Suggestive
Sjogren syndromeOpen Targets
0.00Suggestive
clear cell renal carcinomaOpen Targets
0.00Suggestive
colorectal adenocarcinomaOpen Targets
0.00Suggestive
esophageal cancerOpen Targets
0.00Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ABOShared pathway100%AMY2BShared pathway100%LCTShared pathway100%SIShared pathway100%TPD52L2Shared pathway100%B4GALT3Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
39%
Lung
22%
Heart
10%
Ovary
4%
Liver
2%
Gene Interaction Network
Click a node to explore
LANCL3ABOAMY2BLCTSITPD52L2B4GALT3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q6ZV70
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.05LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.72 [0.50–1.05]
RankingsWhere LANCL3 stands among ~20K protein-coding genes
  • #18,357of 20,598
    Most Researched5
  • #10,546of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedLANCL3
Sources retrieved3 papers
Response time—
📄 Sources
3
1
Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome.
PMID: 28555782
Transfusion · 2017
1.00
2
LanCL proteins are not Involved in Lanthionine Synthesis in Mammals.
PMID: 28106097
Sci Rep · 2017
0.67
3
LanCLs add glutathione to dehydroamino acids generated at phosphorylated sites in the proteome.
PMID: 33932340
Cell · 2021
0.33