Incidental Mutation 'F5426:Sh2d1b1'

• ID: 588
• Institutional Source: Beutler Lab
• Gene Symbol: Sh2d1b1
• Ensembl Gene: ENSMUSG00000102418
• Gene Name: SH2 domain containing 1B1
• Synonyms: Eat2a, Eat2, Sh2d1b, EAT-2
• Essential gene?: Probably non essential (E-score: 0.061)
• Stock #: F5426 (G1) of strain 24G1
• Status: Validated
• Chromosome: 1
• Chromosomal Location: 170104889-170114338 bp(+) (GRCm39)
• Type of Mutation: splice site
• DNA Base Change (assembly): C to A at 170107350 bp (GRCm39)
• Zygosity: Heterozygous
• Ref Sequence: ENSEMBL: ENSMUSP00000137069
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000179976]
• AlphaFold: no structure available at present
• Predicted Effect: probably null; Transcript: ENSMUST00000179976
• SMART Domains: Protein: ENSMUSP00000137069; Gene: ENSMUSG00000102418

Domain	Start	End	E-Value	Type
SH2	3	92	1.05e-26	SMART

• Meta Mutation Damage Score: 0.9755
• Coding Region Coverage:
  • 1x: 78.1%
  • 3x: 56.4%
• Het Detection Efficiency: 35.2%
• Validation Efficiency: 91% (29/32)
• MGI Phenotype: FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] By binding phosphotyrosines through its free SRC (MIM 190090) homology-2 (SH2) domain, EAT2 regulates signal transduction through receptors expressed on the surface of antigen-presenting cells (Morra et al., 2001 [PubMed 11689425]).[supplied by OMIM, Mar 2008] ; PHENOTYPE: Mice homozygous for a knock-out allele exhibit NK cells with enhanced cytolytic capacity and an increased IFN-gamma secretion. Mice homozygous for a different knock-out allele exhibit impaired NK cell cytolysis. [provided by MGI curators]
• Allele List at MGI:

  All alleles(4) : Targeted, knock-out(4)

• Posted On: 2011-03-08

Nature of Mutation

DNA sequencing using the SOLiD technique identified a C to A transversion at base pair 172209912 in the Genbank genomic region NC_000067 for the Sh2d1b1 gene on chromosome 1 (TCCCCAACAG ->TCCCCAAAAG). The mutation is located within intron 1 from the ATG exon, three nucleotides to the next exon. The Sh2d1b1 gene contains 4 total exons using Genbank record NM_012009.4 . The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Sh2d1b1 gene encodes a 132 amino acid protein that plays a role in controlling signal transduction through at least four receptors, CD84, SLAMF1, LY9 and CD244, expressed on the surface of professional antigen-presenting cells.  The protein binds to phosphorylated receptors and contains an SH2 domain at residues 5-101 (Uniprot O35324). Mice homozygous for a knock-out allele exhibit natural killer (NK) cells with enhanced cytolytic capacity and an increased IFN-gamma secretion. Mice homozygous for a different knock-out allele exhibit impaired NK cell cytolysis.