Incidental Mutation 'R6035:Shh'
ID 479132
Institutional Source Beutler Lab
Gene Symbol Shh
Ensembl Gene ENSMUSG00000002633
Gene Name sonic hedgehog
Synonyms Hhg1
MMRRC Submission 044207-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6035 (G1)
Quality Score 225.009
Status Not validated
Chromosome 5
Chromosomal Location 28661838-28672099 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 28666397 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Alanine to Valine at position 163 (A163V)
Ref Sequence ENSEMBL: ENSMUSP00000002708 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000002708]
AlphaFold Q62226
PDB Structure A POTENTIAL CATALYTIC SITE WITHIN THE AMINO-TERMINAL SIGNALLING DOMAIN OF SONIC HEDGEHOG [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN HUMAN HEDGEHOG-INTERACTING PROTEIN HIP AND SONIC HEDGEHOG IN THE PRESENCE OF CALCIUM [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN HUMAN HEDGEHOG-INTERACTING PROTEIN HIP AND SONIC HEDGEHOG WITHOUT CALCIUM [X-RAY DIFFRACTION]
Crystal Structure of Sonic Hedgehog Bound to the third FNIII domain of CDO [X-RAY DIFFRACTION]
Crystal Structure of ShhN [X-RAY DIFFRACTION]
Crystal structure of the Sonic Hedgehog-chondroitin-4-sulphate complex [X-RAY DIFFRACTION]
Crystal structure of the Sonic Hedgehog-heparin complex [X-RAY DIFFRACTION]
Predicted Effect probably damaging
Transcript: ENSMUST00000002708
AA Change: A163V

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000002708
Gene: ENSMUSG00000002633
AA Change: A163V

DomainStartEndE-ValueType
signal peptide 1 24 N/A INTRINSIC
Pfam:HH_signal 25 185 5.6e-92 PFAM
HintN 197 305 1.21e-30 SMART
HintC 310 355 4.58e-8 SMART
low complexity region 359 379 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000180828
Predicted Effect noncoding transcript
Transcript: ENSMUST00000180878
Coding Region Coverage
  • 1x: 99.8%
  • 3x: 98.9%
  • 10x: 91.8%
  • 20x: 70.9%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]
PHENOTYPE: Heterozygotes exhibit shortening of all digits, holes between the frontal bones, dyssymphyses between cervical vertebrae and bony plates over many ribs. Homozygotes usually die before E12, are short-limbed dwarfs and lack forefeet, hindfeet, eyes, ears, external genitalia and a mouth. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 80 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2m G T 6: 121,615,353 (GRCm39) G76W probably damaging Het
Abca17 A T 17: 24,500,219 (GRCm39) F1324Y possibly damaging Het
Abca8b A T 11: 109,862,686 (GRCm39) probably null Het
Abcc12 A G 8: 87,244,033 (GRCm39) M1040T probably damaging Het
Abtb1 A G 6: 88,818,788 (GRCm39) F7L probably damaging Het
Adcy9 T C 16: 4,122,377 (GRCm39) T558A probably benign Het
Adgrb1 A T 15: 74,412,292 (GRCm39) T424S possibly damaging Het
Afg3l2 G T 18: 67,554,329 (GRCm39) L458M probably damaging Het
Ankrd31 C A 13: 96,968,721 (GRCm39) P786Q probably benign Het
Arhgap39 G T 15: 76,621,424 (GRCm39) Y392* probably null Het
Ash1l T C 3: 88,892,326 (GRCm39) Y1402H probably damaging Het
Carmil2 G T 8: 106,419,195 (GRCm39) W749L probably benign Het
Ccar1 A G 10: 62,587,564 (GRCm39) Y867H unknown Het
Cdh13 A G 8: 119,232,437 (GRCm39) D47G probably benign Het
Chst9 T A 18: 15,585,910 (GRCm39) T218S probably benign Het
Clec2i G A 6: 128,870,587 (GRCm39) V67I probably benign Het
Cox7a2 T A 9: 79,667,028 (GRCm39) probably benign Het
Cplx3 A G 9: 57,519,030 (GRCm39) probably null Het
Cpz A G 5: 35,674,929 (GRCm39) C107R probably damaging Het
Dapk1 T A 13: 60,909,013 (GRCm39) C1209S possibly damaging Het
Ddx41 T C 13: 55,681,781 (GRCm39) M307V probably benign Het
Defa24 A G 8: 22,224,565 (GRCm39) I5V probably benign Het
Dgcr8 A T 16: 18,076,178 (GRCm39) N2K probably damaging Het
Ebf2 A G 14: 67,476,423 (GRCm39) D131G probably damaging Het
Fam149b C T 14: 20,427,985 (GRCm39) R424C probably damaging Het
Fbln2 G A 6: 91,240,335 (GRCm39) V714M probably damaging Het
Fgf5 T C 5: 98,423,385 (GRCm39) Y257H probably damaging Het
Fmo3 A C 1: 162,791,605 (GRCm39) V224G probably damaging Het
Gigyf2 T C 1: 87,338,450 (GRCm39) I394T possibly damaging Het
Glmn T A 5: 107,741,746 (GRCm39) probably null Het
Greb1l T C 18: 10,501,025 (GRCm39) I385T possibly damaging Het
Grhl1 C A 12: 24,658,449 (GRCm39) Q365K probably benign Het
Gsdme G A 6: 50,206,306 (GRCm39) T179M probably damaging Het
Gtf2a1l A G 17: 89,018,962 (GRCm39) T349A probably benign Het
Hax1 GTCATCATCATCATCATC GTCATCATCATCATCATCATC 3: 89,905,247 (GRCm39) probably benign Het
Il5ra G A 6: 106,718,226 (GRCm39) T76I probably damaging Het
Itga8 T C 2: 12,196,525 (GRCm39) T631A probably benign Het
Kcnh6 G A 11: 105,909,978 (GRCm39) probably null Het
Krt26 C T 11: 99,224,415 (GRCm39) E368K probably benign Het
Lhx9 T C 1: 138,766,281 (GRCm39) D169G possibly damaging Het
Lmod3 A G 6: 97,224,234 (GRCm39) L529P probably damaging Het
Mroh2a G A 1: 88,158,390 (GRCm39) V146M probably damaging Het
Nup155 A G 15: 8,173,577 (GRCm39) T891A probably benign Het
Or11g24 A G 14: 50,661,984 (GRCm39) T3A probably benign Het
Or1e1 T C 11: 73,244,582 (GRCm39) M1T probably null Het
Or1j13 T A 2: 36,369,996 (GRCm39) I49F probably damaging Het
Or1p4-ps1 T C 11: 74,208,285 (GRCm39) *145R probably null Het
Or8b36 ATTGCTGTTT ATTGCTGTTTGCTGTTT 9: 37,937,836 (GRCm39) probably null Het
Papln G C 12: 83,821,454 (GRCm39) G262A probably damaging Het
Pdcd1lg2 G A 19: 29,423,435 (GRCm39) V160I probably benign Het
Pde8b A G 13: 95,164,105 (GRCm39) probably benign Het
Ppme1 G A 7: 100,004,002 (GRCm39) R68* probably null Het
Ptprn2 A T 12: 117,219,215 (GRCm39) N949Y probably damaging Het
Qser1 C A 2: 104,617,468 (GRCm39) D1115Y probably damaging Het
Rad54l G T 4: 115,954,666 (GRCm39) D674E probably damaging Het
Ripk4 T A 16: 97,545,387 (GRCm39) D420V probably damaging Het
Ros1 G T 10: 51,954,067 (GRCm39) S1857R probably benign Het
Rsf1 ATGGCG ATGGCGACGGTGGCG 7: 97,229,111 (GRCm39) probably benign Het
Rsf1 A G 7: 97,311,316 (GRCm39) E682G probably benign Het
Samd4 G A 14: 47,325,329 (GRCm39) R515H probably damaging Het
Selp T A 1: 163,969,079 (GRCm39) W560R probably benign Het
Shc3 A T 13: 51,615,468 (GRCm39) L163Q probably damaging Het
Slc17a8 T C 10: 89,427,937 (GRCm39) R113G possibly damaging Het
Slc5a6 C A 5: 31,206,168 (GRCm39) probably benign Het
Smarcd2 A G 11: 106,157,715 (GRCm39) probably null Het
Sytl3 A G 17: 6,995,664 (GRCm39) D148G probably damaging Het
Tnks G T 8: 35,385,615 (GRCm39) H297Q possibly damaging Het
Trbv21 A T 6: 41,179,568 (GRCm39) probably benign Het
Ube3c T C 5: 29,806,161 (GRCm39) F268L probably benign Het
Ugt2b5 T C 5: 87,287,541 (GRCm39) I209V probably benign Het
Usp1 A G 4: 98,818,082 (GRCm39) N140S probably damaging Het
Vcam1 T C 3: 115,919,606 (GRCm39) Y226C probably damaging Het
Vmn1r129 T A 7: 21,094,534 (GRCm39) Q228L probably damaging Het
Vmn1r209 T A 13: 22,990,202 (GRCm39) N163Y probably benign Het
Vmn1r85 A G 7: 12,818,854 (GRCm39) S97P probably damaging Het
Vmn2r30 C T 7: 7,337,350 (GRCm39) M95I probably benign Het
Vmn2r74 G A 7: 85,601,098 (GRCm39) R847C probably damaging Het
Wdr70 G A 15: 7,916,830 (GRCm39) T529I possibly damaging Het
Zfp532 T G 18: 65,757,005 (GRCm39) S313A possibly damaging Het
Zhx3 A T 2: 160,621,463 (GRCm39) N901K probably benign Het
Other mutations in Shh
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL03066:Shh APN 5 28,666,369 (GRCm39) missense probably damaging 1.00
BB005:Shh UTSW 5 28,666,404 (GRCm39) missense possibly damaging 0.88
BB015:Shh UTSW 5 28,666,404 (GRCm39) missense possibly damaging 0.88
R2484:Shh UTSW 5 28,671,740 (GRCm39) missense probably benign 0.22
R4153:Shh UTSW 5 28,662,947 (GRCm39) missense probably damaging 1.00
R4352:Shh UTSW 5 28,663,187 (GRCm39) missense probably benign
R4668:Shh UTSW 5 28,662,853 (GRCm39) makesense probably null
R5371:Shh UTSW 5 28,671,688 (GRCm39) missense probably damaging 1.00
R5407:Shh UTSW 5 28,671,578 (GRCm39) nonsense probably null
R6035:Shh UTSW 5 28,666,397 (GRCm39) missense probably damaging 1.00
R7650:Shh UTSW 5 28,663,304 (GRCm39) missense probably benign 0.01
R7762:Shh UTSW 5 28,671,664 (GRCm39) missense probably benign 0.00
R7873:Shh UTSW 5 28,663,298 (GRCm39) missense possibly damaging 0.71
R7928:Shh UTSW 5 28,666,404 (GRCm39) missense possibly damaging 0.88
R8682:Shh UTSW 5 28,663,058 (GRCm39) missense probably benign 0.00
R8767:Shh UTSW 5 28,671,487 (GRCm39) missense possibly damaging 0.94
R8827:Shh UTSW 5 28,663,125 (GRCm39) missense probably damaging 1.00
R9300:Shh UTSW 5 28,663,461 (GRCm39) missense probably damaging 1.00
X0019:Shh UTSW 5 28,666,538 (GRCm39) missense probably damaging 1.00
Predicted Primers
Posted On 2017-06-26