LBX1

Gene Facts

• HGNC Symbol: LBX1 (HGNC:16960)
• HGNC Name: ladybird homeobox 1
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: LBX1H, HPX6
• %HI: 1.88
• pLI: 0.44
• LOEUF: 0.75
• Cytoband: 10q24.32
• Genomic Coordinates:

  GRCh37/hg19:	chr10:102986751-102989220
  GRCh38/hg38:	chr10:101226994-101229463

• MANE Select Transcript: NM_006562.5 ENST00000370193.4
• Function: Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord. {ECO:0000250}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-15110
• ClinGen Curation ID: CCID:007392
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: No Evidence for Haploinsufficiency (0)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 08/21/2014

Haploinsufficiency (HI) Score Details

• HI Score: 0
• HI Evidence Strength: No Evidence for Haploinsufficiency

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity

TS Disease

• split hand-foot malformation 3

• TS Evidence Comments: Tandem duplications at 10q24 are associated with split hand/foot malformation 3 (SHFM3) syndrome: PMID: 12913067 De Mollerat (2003): This is a report of 7 patients with SHFM3 (split hand/foot malformation 3) who all had a tandem duplication which included LBX1, BTRC, and POLL, and had a breakpoint within FBXW4 (DAC). PMID: 16235095 Kano (2005): This report includes 2 patients with SHFM3 who had similar duplications that include LBX1. In addition to LBX1, one duplication included all of BTRC, POLL, and DPCD, and had a breakpoint within FBXW4 (DAC). The other duplication encompassed all of FBXW4. PMID: 19584065 Dimitrov (2010): This paper include 6 patients with both syndromic and non-syndromic SHFM3 who have duplications at 10q24 of varying size, which include LBX1. They comment on genotype-phenotype correlations. Of note: Fernandez-Jaen et al. (2014) (24782348 ) report a 130kb duplication including only LBX1 in a 12-year-old Spanish female patient with congenital scoliosis due to a complex anterior central malformation of the cervical and dorsal vertebrae, as well as severe hypotrophy of paravertebral muscles and deficient fine and gross motor skills. The girl also exhibited attention problems, poor working memory, and "very low academic performance" (not otherwise characterized). The duplication was also found in a paternal aunt with "early onset progressive myopathy and a severe physical disability present since young adulthood" requiring use of a wheelchair. The authors do not specifically comment on whether or not the girl's father was tested, though they do note that he did not comply with requests for a spine MRI. Upon reported initial examination, he was deemed healthy with no dysmorphic features, physical malformations, or learning problems noted. The authors discuss the role of this gene in muscle development and preservation in animal models, as well as associations made between particular SNPs in this gene and idiopathic adolescent scoliosis in a GWAS study of a Japanese population. Larger microduplications of 10q24, including LBX1 and other genes, are associated with split hand/foot malformation 3 (SHFM3), a condition characterized by reduced penetrance and variable expressivitiy; these authors note however that, to date, there have been no reports of SHFM3 with described scoliosis, vertebrae malformations,or myopathy.