Incidental Mutation 'D4043:Tulp3'
ID254
Institutional Source Beutler Lab
Gene Symbol Tulp3
Ensembl Gene ENSMUSG00000001521
Gene Nametubby-like protein 3
Synonyms2310022L06Rik
Accession Numbers

Genbank: NM_011657; MGI: 1329045

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome6
Chromosomal Location128321161-128355851 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to A at 128324150 bp
ZygosityHeterozygous
Amino Acid Change Serine to Leucine at position 366 (S366L)
Ref Sequence ENSEMBL: ENSMUSP00000001562 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001562]
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 0.202 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
1110020G09Rik T A 15: 9,103,385 probably benign Homo
1700029J07Rik A G 8: 45,956,403 V293A probably damaging Het
Adam29 A T 8: 55,872,461 C319* probably null Het
Adgrg1 T C 8: 95,005,229 probably null Homo
Ago3 A T 4: 126,351,003 V630E probably damaging Het
Armc8 G T 9: 99,483,976 N628K probably benign Het
Chd7 A G 4: 8,862,650 D2579G probably damaging Het
Duox1 G A 2: 122,344,795 C1358Y probably benign Het
Fam208a A G 14: 27,471,992 I1050V probably benign Het
Ftsj3 C A 11: 106,254,808 M66I possibly damaging Homo
Iqub C T 6: 24,505,751 E53K possibly damaging Het
Kirrel T A 3: 87,083,203 T771S probably benign Het
Lrrc66 A T 5: 73,607,526 S725T probably benign Het
Mael T C 1: 166,236,886 I104M probably benign Homo
Mkks C T 2: 136,874,610 V457I probably benign Het
Npas1 T C 7: 16,463,244 probably null Het
Ocrl T C X: 47,936,323 V359A probably benign Homo
Olfr1065 G A 2: 86,445,220 T254M probably damaging Het
Pde6b C T 5: 108,425,356 R531* probably null Het
Polr1a G A 6: 71,941,417 C653Y possibly damaging Het
Rbm26 A G 14: 105,152,540 V216A possibly damaging Het
Rin2 C A 2: 145,822,363 H52Q possibly damaging Het
Ssc5d C T 7: 4,943,983 T1112I possibly damaging Het
Sv2c C T 13: 96,088,481 V107M probably benign Het
Zfp831 T A 2: 174,645,266 V578E probably benign Homo
Other mutations in Tulp3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01025:Tulp3 APN 6 128325884 missense probably damaging 0.99
IGL01327:Tulp3 APN 6 128327634 missense probably damaging 1.00
IGL01382:Tulp3 APN 6 128325070 missense probably damaging 1.00
IGL01633:Tulp3 APN 6 128325960 missense probably damaging 1.00
IGL02228:Tulp3 APN 6 128334485 missense probably damaging 1.00
IGL02372:Tulp3 APN 6 128327598 missense possibly damaging 0.92
R0243:Tulp3 UTSW 6 128325958 nonsense probably null
R1181:Tulp3 UTSW 6 128325952 missense possibly damaging 0.47
R1673:Tulp3 UTSW 6 128333943 unclassified probably null
R1749:Tulp3 UTSW 6 128337759 missense probably damaging 1.00
R1984:Tulp3 UTSW 6 128326806 missense probably benign 0.02
R1985:Tulp3 UTSW 6 128326806 missense probably benign 0.02
R2568:Tulp3 UTSW 6 128327638 missense probably benign 0.00
R4660:Tulp3 UTSW 6 128323054 utr 3 prime probably benign
R4779:Tulp3 UTSW 6 128323120 missense probably damaging 1.00
R5001:Tulp3 UTSW 6 128325068 missense probably damaging 1.00
R6192:Tulp3 UTSW 6 128355740 splice site probably null
R6242:Tulp3 UTSW 6 128323087 missense probably damaging 1.00
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 On2010-08-09