Incidental Mutation 'D4043:Tulp3'
ID 254
Institutional Source Beutler Lab
Gene Symbol Tulp3
Ensembl Gene ENSMUSG00000001521
Gene Name tubby-like protein 3
Synonyms 2310022L06Rik
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome 6
Chromosomal Location 128298124-128332814 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 128301113 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Leucine at position 366 (S366L)
Ref Sequence ENSEMBL: ENSMUSP00000001562 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001562]
AlphaFold O88413
Predicted Effect probably benign
Transcript: ENSMUST00000001562
AA Change: S366L

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000001562
Gene: ENSMUSG00000001521
AA Change: S366L

DomainStartEndE-ValueType
Pfam:Tub_N 30 84 1.7e-23 PFAM
Pfam:Tub_N 76 198 5.5e-16 PFAM
Pfam:Tub 213 454 1e-87 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000128708
Meta Mutation Damage Score 0.2777 question?
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.] This gene encodes a member of the tubby gene family of bipartite transcription factors. Members of this family have been identified in plants, vertebrates, and invertebrates, and they share a conserved N-terminal transcription activation region and a conserved C-terminal DNA and phosphatidylinositol-phosphate binding region. The encoded protein binds to phosphoinositides in the plasma membrane via its C-terminal region and probably functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis, for instance, induced by G-protein-coupled-receptor signaling. It plays an important role in neuronal development and function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2009]
PHENOTYPE: Homozygous mutant mice exhibit failed neural tube closure followed by neuroepithelial apoptosis and ultimately embryonic death around E14.5. Heterozygotes are largely phenotypically normal, however some exhibit neuroepithelial apoptosis and die as embryos. [provided by MGI curators]
Allele List at MGI

All alleles(35) : Targeted, other(3) Gene trapped(31) Chemically induced(1)
Other mutations in this stock
Total: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam29 A T 8: 56,325,496 (GRCm39) C319* probably null Het
Adgrg1 T C 8: 95,731,857 (GRCm39) probably null Homo
Ago3 A T 4: 126,244,796 (GRCm39) V630E probably damaging Het
Armc8 G T 9: 99,366,029 (GRCm39) N628K probably benign Het
Cfap96 A G 8: 46,409,440 (GRCm39) V293A probably damaging Het
Chd7 A G 4: 8,862,650 (GRCm39) D2579G probably damaging Het
Duox1 G A 2: 122,175,276 (GRCm39) C1358Y probably benign Het
Ftsj3 C A 11: 106,145,634 (GRCm39) M66I possibly damaging Homo
Iqub C T 6: 24,505,750 (GRCm39) E53K possibly damaging Het
Kirrel1 T A 3: 86,990,510 (GRCm39) T771S probably benign Het
Lrrc66 A T 5: 73,764,869 (GRCm39) S725T probably benign Het
Mael T C 1: 166,064,455 (GRCm39) I104M probably benign Homo
Mkks C T 2: 136,716,530 (GRCm39) V457I probably benign Het
Nadk2 T A 15: 9,103,473 (GRCm39) probably benign Homo
Npas1 T C 7: 16,197,169 (GRCm39) probably null Het
Ocrl T C X: 47,025,200 (GRCm39) V359A probably benign Homo
Or8k27 G A 2: 86,275,564 (GRCm39) T254M probably damaging Het
Pde6b C T 5: 108,573,222 (GRCm39) R531* probably null Het
Polr1a G A 6: 71,918,401 (GRCm39) C653Y possibly damaging Het
Rbm26 A G 14: 105,389,976 (GRCm39) V216A possibly damaging Het
Rin2 C A 2: 145,664,283 (GRCm39) H52Q possibly damaging Het
Ssc5d C T 7: 4,946,982 (GRCm39) T1112I possibly damaging Het
Sv2c C T 13: 96,224,989 (GRCm39) V107M probably benign Het
Tasor A G 14: 27,193,949 (GRCm39) I1050V probably benign Het
Zfp831 T A 2: 174,487,059 (GRCm39) V578E probably benign Homo
Other mutations in Tulp3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01025:Tulp3 APN 6 128,302,847 (GRCm39) missense probably damaging 0.99
IGL01327:Tulp3 APN 6 128,304,597 (GRCm39) missense probably damaging 1.00
IGL01382:Tulp3 APN 6 128,302,033 (GRCm39) missense probably damaging 1.00
IGL01633:Tulp3 APN 6 128,302,923 (GRCm39) missense probably damaging 1.00
IGL02228:Tulp3 APN 6 128,311,448 (GRCm39) missense probably damaging 1.00
IGL02372:Tulp3 APN 6 128,304,561 (GRCm39) missense possibly damaging 0.92
R0243:Tulp3 UTSW 6 128,302,921 (GRCm39) nonsense probably null
R1181:Tulp3 UTSW 6 128,302,915 (GRCm39) missense possibly damaging 0.47
R1673:Tulp3 UTSW 6 128,310,906 (GRCm39) splice site probably null
R1749:Tulp3 UTSW 6 128,314,722 (GRCm39) missense probably damaging 1.00
R1984:Tulp3 UTSW 6 128,303,769 (GRCm39) missense probably benign 0.02
R1985:Tulp3 UTSW 6 128,303,769 (GRCm39) missense probably benign 0.02
R2568:Tulp3 UTSW 6 128,304,601 (GRCm39) missense probably benign 0.00
R4660:Tulp3 UTSW 6 128,300,017 (GRCm39) utr 3 prime probably benign
R4779:Tulp3 UTSW 6 128,300,083 (GRCm39) missense probably damaging 1.00
R5001:Tulp3 UTSW 6 128,302,031 (GRCm39) missense probably damaging 1.00
R6192:Tulp3 UTSW 6 128,332,703 (GRCm39) splice site probably null
R6242:Tulp3 UTSW 6 128,300,050 (GRCm39) missense probably damaging 1.00
R7464:Tulp3 UTSW 6 128,303,792 (GRCm39) missense probably benign 0.00
R7782:Tulp3 UTSW 6 128,301,943 (GRCm39) missense possibly damaging 0.69
R7883:Tulp3 UTSW 6 128,303,807 (GRCm39) missense probably damaging 1.00
R8027:Tulp3 UTSW 6 128,311,436 (GRCm39) missense probably benign 0.00
R8235:Tulp3 UTSW 6 128,304,640 (GRCm39) missense probably benign 0.00
R8919:Tulp3 UTSW 6 128,310,966 (GRCm39) missense probably benign 0.12
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to T transition at position 1170 of the Tulp3 transcript in exon 10 of 11 total exons. Multiple transcripts of the Tulp3 gene are displayed on Ensembl and Vega. The mutated nucleotide causes a serine to leucine substitution at amino acid 366 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Tulp3 gene encodes a 460 amino acid protein that functions in signal transduction from heterotrimeric G protein-coupled receptors (GPCRs). The protein binds to phosphorylated inositol lipids, and negatively regulates Sonic Hedgehog (SHH) signaling (Uniprot O88413). Homozygous mutant mice exhibit failed neural tube closure followed by neuroepithelial apoptosis and ultimately embryonic death around E14.5. Heterozygotes are largely phenotypically normal, however some exhibit neuroepithelial apoptosis and die as embryos.  
 
The S366L change is predicted to be benign by the PolyPhen program.
Posted On 2010-08-09