ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype

Haploinsufficiency phenotype comments:

While haploinsufficiency for LMBR1 has not been observed, a homozygous 4- to 6-kb intragenic LMBR1 deletion, predicted to result in a loss-of-function, is associated with the autosomal recessive condition, Acheiropodia [MIM #200500].

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

While the triplosensitivity score for LMBR1 is currently 0, a region contained within this gene has a triplosensitivity score of 3. It is recommended that any duplication involving LMBR1 be carefully evaluated in the context of clinical phenotype. See background information and linked ZRS region below. Background: The LMBR1 gene contains a regulatory element for the SHH gene, the ZRS, within intron 5. Gain-of-function type mutations involving the ZRS, including intragenic LMBR1 duplications, have been reported in association with autosomal dominant limb malformation phenotypes. As the pathogenic mechanism of ZRS duplication is still unclear, it is not known whether duplications encompassing the entire LMBR1 gene would result in similar phenotypes.