Incidental Mutation 'ZE80:Tspan12'
ID20
Institutional Source Beutler Lab
Gene Symbol Tspan12
Ensembl Gene ENSMUSG00000029669
Gene Nametetraspanin 12
SynonymsTm4sf12
Accession Numbers

Genbank: NM_173007; MGI: 1889818

Is this an essential gene? Probably non essential (E-score: 0.197) question?
Stock #ZE80 of strain atchoum
Quality Score
Status Validated
Chromosome6
Chromosomal Location21771395-21852515 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 21795609 bp
ZygosityHomozygous
Amino Acid Change Histidine to Arginine at position 194 (H194R)
Ref Sequence ENSEMBL: ENSMUSP00000031678 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000031678] [ENSMUST00000120965] [ENSMUST00000123116] [ENSMUST00000134635]
Predicted Effect probably benign
Transcript: ENSMUST00000031678
AA Change: H194R

PolyPhen 2 Score 0.144 (Sensitivity: 0.92; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000031678
Gene: ENSMUSG00000029669
AA Change: H194R

DomainStartEndE-ValueType
Pfam:Tetraspannin 9 248 1.1e-42 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000120965
SMART Domains Protein: ENSMUSP00000113384
Gene: ENSMUSG00000029669

DomainStartEndE-ValueType
Pfam:Tetraspannin 9 156 4.1e-23 PFAM
transmembrane domain 180 202 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000123116
AA Change: H194R

PolyPhen 2 Score 0.093 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000117820
Gene: ENSMUSG00000029669
AA Change: H194R

DomainStartEndE-ValueType
Pfam:Tetraspannin 9 203 4.1e-33 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000134635
SMART Domains Protein: ENSMUSP00000123475
Gene: ENSMUSG00000029669

DomainStartEndE-ValueType
Pfam:Tetraspannin 9 129 1.8e-20 PFAM
Meta Mutation Damage Score 0.0665 question?
Coding Region Coverage
  • 1x: 85.7%
  • 3x: 64.9%
Validation Efficiency 80% (82/103)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit abnormal retinal vasculature with pericapillary occlusions, lack of vertical sprouts, gliosis, fenestration, microanurysms, hemorrhage, and delayed regression of hyaloid capillaries. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 2 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
AW551984 T C 9: 39,593,667 probably null Homo
Dopey1 T C 9: 86,500,842 V276A probably damaging Het
Other mutations in Tspan12
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00843:Tspan12 APN 6 21851082 utr 5 prime probably benign
IGL02601:Tspan12 APN 6 21835379 unclassified probably benign
IGL02992:Tspan12 APN 6 21799877 critical splice donor site probably null
PIT4362001:Tspan12 UTSW 6 21835464 missense possibly damaging 0.87
R1800:Tspan12 UTSW 6 21795700 missense probably damaging 1.00
R1862:Tspan12 UTSW 6 21851023 missense probably damaging 1.00
R1898:Tspan12 UTSW 6 21795694 missense probably damaging 0.97
R2101:Tspan12 UTSW 6 21799888 missense probably benign 0.00
R2351:Tspan12 UTSW 6 21835507 missense probably benign
R4820:Tspan12 UTSW 6 21795661 missense probably damaging 0.99
R4921:Tspan12 UTSW 6 21835449 missense possibly damaging 0.66
R5284:Tspan12 UTSW 6 21835467 missense probably damaging 0.97
R5341:Tspan12 UTSW 6 21835459 missense possibly damaging 0.69
R5372:Tspan12 UTSW 6 21772699 missense probably benign 0.06
R5929:Tspan12 UTSW 6 21772747 missense possibly damaging 0.92
R6052:Tspan12 UTSW 6 21772638 missense probably benign 0.09
R6108:Tspan12 UTSW 6 21772771 missense probably benign
R6207:Tspan12 UTSW 6 21799908 missense probably damaging 1.00
R6248:Tspan12 UTSW 6 21799971 missense probably damaging 1.00
R7014:Tspan12 UTSW 6 21772919 missense probably benign 0.01
R7457:Tspan12 UTSW 6 21772683 missense probably benign 0.09
R7776:Tspan12 UTSW 6 21836443 missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 917 of the Tspan12 transcript, in exon 8 of 9 total exons. Multiple transcripts of Tspan12 are displayed on Ensembl. The mutated nucleotide causes a histidine to arginine substitution at amino acid 194 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
Tspan12 encodes the 305 amino acid Tetraspanin-12 protein with evidence at the transcript level. Tetraspanin-12 belongs to the tetraspanin family and has four transmembrane domains. Both the N- and C-termini are cytoplasmic. Tetraspanins are involved in organizing other proteins into a network of multimolecular membrane microdomains, sometimes called the tetraspanin web. Within the tetraspanin web, tetraspanin proteins can associate not only with integrins and other transmembrane proteins, but also with signaling enzymes such as protein kinase C and phosphatidylinositol-4 kinase (Uniprot Q8BKT6). 
 
The H194R change occurs in the second extracellular domain of the protein, and is predicted to be probably damaging by the PolyPhen program. 
Note

This stock (ZE80) also contains mutations present in atchoum stock A9681.  The overlapping mutations are Ablim1, Gm9943, Olfr664, Ints1, and Pld1.

Posted On2009-11-12