Incidental Mutation 'D4043:Pde6b'

• ID: 257
• Institutional Source: Beutler Lab
• Gene Symbol: Pde6b
• Ensembl Gene: ENSMUSG00000029491
• Gene Name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
• Synonyms: rd, rd10, rd1, r, Pdeb
• Essential gene?: Non essential (E-score: 0.000)
• Stock #: D4043 (G3) of strain 483
• Status: Validated
• Chromosome: 5
• Chromosomal Location: 108536239-108579609 bp(+) (GRCm39)
• Type of Mutation: nonsense
• DNA Base Change (assembly): C to T at 108573222 bp (GRCm39)
• Zygosity: Heterozygous
• Amino Acid Change: Arginine to Stop codon at position 531 (R531*)
• Ref Sequence: ENSEMBL: ENSMUSP00000031456
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000031456]
• AlphaFold: P23440
• Predicted Effect: probably null; Transcript: ENSMUST00000031456; AA Change: R531*
• SMART Domains: Protein: ENSMUSP00000031456; Gene: ENSMUSG00000029491; AA Change: R531*

Domain	Start	End	E-Value	Type
GAF	71	230	1.29e-27	SMART
GAF	252	439	5.76e-25	SMART
Blast:HDc	484	538	1e-24	BLAST
HDc	554	732	1.25e-9	SMART
Blast:HDc	757	792	8e-13	BLAST
low complexity region	813	837	N/A	INTRINSIC

• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000134865
• Meta Mutation Damage Score: 0.9754
• Coding Region Coverage:
  • 1x: 88.8%
  • 3x: 72.5%
• Validation Efficiency: 88% (220/249)
• MGI Phenotype: FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Photon absorption triggers a signaling cascade in rod photoreceptors that activates cGMP phosphodiesterase (PDE), resulting in the rapid hydrolysis of cGMP, closure of cGMP-gated cation channels, and hyperpolarization of the cell. PDE is a peripheral membrane heterotrimeric enzyme made up of alpha, beta, and gamma subunits. This gene encodes the beta subunit. Mutations in this gene result in retinitis pigmentosa and autosomal dominant congenital stationary night blindness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009] ; PHENOTYPE: Homozygotes for the rd1 mutation have severe retinal degeneration and vision loss. Rod cells are lost by 35 days of age; cone cells degenerate slower and some light sensitivity persists. Other allelic mutations produce similar or milder phenotypes. [provided by MGI curators]
• Allele List at MGI:

  All alleles(13) : Targeted, knock-out(1) Targeted, other(1) Spontaneous(2) Chemically induced(9)

• Posted On: 2010-08-09

Nature of Mutation

DNA sequencing using the SOLiD technique identified a C to T transition at position 1658 of the Ptranscript in exon 12 of 22 total exons.  Three transcripts of the Pde6b gene are displayed on Ensembl and Vega. The mutated nucleotide introduces a premature stop codon at arginine 531 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

Pde6b encodes the 856 amino acid rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta (PDE6B). PDE6 is the rod-specific cGMP phosphodiesterase, and is a critical component of the phototransduction cascade in rod photoreceptors downstream of rhodopsin. PDE6B is one of the catalytic subunits of PDE6 (Uniprot P23440). Mutations in the Pde6b gene in both mouse and humans cause retinitis pigmentosa with severe retinal degeneration and vision loss (OMIM #268000).

 

The premature stop introduced by the Nd2 mutation in the Pde6b gene truncates 326 amino acids from the C-terminus of the protein. This allele is likely null.