Incidental Mutation 'B6584:Acadl'

• ID: 634
• Institutional Source: Beutler Lab
• Gene Symbol: Acadl
• Ensembl Gene: ENSMUSG00000026003
• Gene Name: acyl-Coenzyme A dehydrogenase, long-chain
• Synonyms: C79855, LCAD
• Essential gene?: Essential (E-score: 1.000)
• Stock #: B6584 (G3) of strain supermodel
• Status: Validated
• Chromosome: 1
• Chromosomal Location: 66869998-66902436 bp(-) (GRCm39)
• Type of Mutation: splice site
• DNA Base Change (assembly): T to A at 66887632 bp (GRCm39)
• Zygosity: Heterozygous
• Ref Sequence: ENSEMBL: ENSMUSP00000027153
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000027153]
• AlphaFold: no structure available at present
• Predicted Effect: probably benign; Transcript: ENSMUST00000027153
• SMART Domains: Protein: ENSMUSP00000027153; Gene: ENSMUSG00000026003

Domain	Start	End	E-Value	Type
low complexity region	2	18	N/A	INTRINSIC
Pfam:Acyl-CoA_dh_N	54	165	1.3e-33	PFAM
Pfam:Acyl-CoA_dh_M	169	266	9.2e-29	PFAM
Pfam:Acyl-CoA_dh_1	278	427	5.1e-44	PFAM
Pfam:Acyl-CoA_dh_2	293	416	3.4e-11	PFAM

• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000121857
• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000139208
• Coding Region Coverage:
  • 1x: 85.5%
  • 3x: 70.0%
• Het Detection Efficiency: 43.9%
• Validation Efficiency: 89% (133/150)
• MGI Phenotype: FUNCTION: This gene encodes a homotetrameric mitochondrial flavoprotein and is a member of the acyl-CoA dehydrogenase family. Members of this family catalyze the first step of fatty acid beta-oxidation, forming a C2-C3 trans-double bond in a FAD-dependent reaction. As beta-oxidation cycles through its four steps, each member of the acyl-CoA dehydrogenase family works at an optimum fatty acid chain-length. This enzyme has its optimum length between C12- and C16-acylCoA. In mice, deficiency of this gene can cause sudden death, cardiomyopathy as well as fasting and cold intolerance. [provided by RefSeq, Nov 2012] ; PHENOTYPE: Homozygous mutation of this gene results in reduced litter size, sudden death between 2-14 weeks of age, reduced serum glucose levels, lipid accumulation in the liver and heart, and cardiomyopathy. Heterozygous mutant animals exhibit reduced litter size. [provided by MGI curators]
• Allele List at MGI:

  All alleles(1) : Targeted, knock-out(1)

• Posted On: 2011-04-12

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at base pair 66895047 NC_000067 for the Acadl gene on chromosome 1 (CCCACTATAG ->CCCTCTATAG). Two  transcripts of the Acadl gene are displayed on Ensembl and Vega. The mutation is located within intron 4 from the ATG exon, seven nucleotides to the next exon. The Acadl gene contains 11 total exons using Genbank record NM_007381.3. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Acadl gene encodes the 430 amino acid long-chain acyl-CoA dehydrogenase (LCAD), an enzyme involved in fatty acid beta-oxidation. (Uniprot P51174).  Homozygous mutation of this gene in mice results in reduced litter size, sudden death between 2-14 weeks of age, reduced serum glucose levels, lipid accumulation in the liver and heart, and cardiomyopathy. Heterozygous mutant animals exhibit reduced litter size. LCAD deficiency (OMIM 201460) in humans causes a defect in mitochondrial fatty acid oxidation with nonketotic hypoglycemia and episodes of cardiorespiratory arrest associated with fasting. Other features included hepatomegaly, cardiomegaly, and hypotonia.