Incidental Mutation 'R5371:Shh'
ID 428712
Institutional Source Beutler Lab
Gene Symbol Shh
Ensembl Gene ENSMUSG00000002633
Gene Name sonic hedgehog
Synonyms Hhg1
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5371 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 28661838-28672099 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 28671688 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Phenylalanine at position 25 (C25F)
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: C25F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000002708
Gene: ENSMUSG00000002633
AA Change: C25F

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
Predicted Effect noncoding transcript
Transcript: ENSMUST00000181202
Meta Mutation Damage Score 0.9558 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 97.0%
  • 20x: 94.6%
Validation Efficiency 96% (71/74)
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: 59 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930432E11Rik G T 7: 29,261,918 (GRCm39) noncoding transcript Het
Arpp21 G A 9: 111,895,000 (GRCm39) P755S probably benign Het
Aspm C T 1: 139,398,279 (GRCm39) Q982* probably null Het
Atp5f1e C T 2: 174,304,319 (GRCm39) probably benign Het
BC024139 A G 15: 76,004,886 (GRCm39) *598Q probably null Het
Bcl6 T A 16: 23,788,736 (GRCm39) D544V possibly damaging Het
Ccdc9 A T 7: 16,014,655 (GRCm39) D195E probably damaging Het
Cd38 A G 5: 44,026,225 (GRCm39) N3S probably benign Het
Cfap46 A T 7: 139,212,097 (GRCm39) probably null Het
Cmtr2 T C 8: 110,948,044 (GRCm39) F118S probably damaging Het
Cyp7a1 A G 4: 6,268,378 (GRCm39) F449S probably damaging Het
Dnah10 C T 5: 124,820,693 (GRCm39) A509V probably benign Het
Dsp A T 13: 38,378,865 (GRCm39) Q1271L probably damaging Het
Edar A C 10: 58,443,274 (GRCm39) V284G possibly damaging Het
Fdft1 A G 14: 63,388,750 (GRCm39) V294A probably damaging Het
Gba1 T A 3: 89,112,778 (GRCm39) V140E probably benign Het
Gm12185 A T 11: 48,806,566 (GRCm39) S208R probably benign Het
Gm21028 C A 7: 42,227,946 (GRCm39) E23* probably null Het
Gm6871 A G 7: 41,222,992 (GRCm39) L32P probably benign Het
Hhip C T 8: 80,724,220 (GRCm39) V341M probably damaging Het
Kcnq2 C A 2: 180,776,813 (GRCm39) V25L probably damaging Het
Krit1 C A 5: 3,881,551 (GRCm39) H548N probably damaging Het
Kynu C T 2: 43,479,406 (GRCm39) A100V probably benign Het
Lpp T C 16: 24,708,554 (GRCm39) C295R probably damaging Het
Mdp1 A G 14: 55,897,806 (GRCm39) V9A probably damaging Het
Mllt3 T C 4: 87,759,093 (GRCm39) I318M possibly damaging Het
Mpzl3 A G 9: 44,966,510 (GRCm39) probably benign Het
Mroh2a A G 1: 88,186,386 (GRCm39) S64G probably benign Het
Mup8 A G 4: 60,222,423 (GRCm39) V16A probably benign Het
Myh13 T A 11: 67,235,616 (GRCm39) probably null Het
Myh4 A T 11: 67,150,150 (GRCm39) Q1869L probably damaging Het
Nt5c G A 11: 115,381,643 (GRCm39) probably null Het
Olfr908 CACAACAACA CACAACA 9: 38,427,434 (GRCm39) probably benign Het
Or13c7b A T 4: 43,821,058 (GRCm39) M101K probably damaging Het
Or51h7 T A 7: 102,591,719 (GRCm39) M22L probably benign Het
Or5d43 C A 2: 88,104,976 (GRCm39) C139F probably damaging Het
Parp11 T C 6: 127,447,755 (GRCm39) F30L probably damaging Het
Pcdhgc3 A T 18: 37,941,507 (GRCm39) D636V possibly damaging Het
Ppp1cb T C 5: 32,643,332 (GRCm39) F234L probably damaging Het
Rras2 A T 7: 113,649,572 (GRCm39) V164E probably damaging Het
Rsf1 GCGGCGGCG GCGGCGGCGACGGCGGCG 7: 97,229,120 (GRCm39) probably benign Het
Scg3 T C 9: 75,568,583 (GRCm39) T390A probably damaging Het
Slc24a1 T C 9: 64,856,550 (GRCm39) K119R unknown Het
Speg G T 1: 75,408,037 (GRCm39) R3244L possibly damaging Het
Spns1 A G 7: 125,972,936 (GRCm39) probably benign Het
Sptbn4 A C 7: 27,059,166 (GRCm39) probably null Het
Stap1 T A 5: 86,244,375 (GRCm39) F214Y possibly damaging Het
Tcerg1 T A 18: 42,652,600 (GRCm39) M76K unknown Het
Tjp1 A T 7: 64,963,059 (GRCm39) Y959* probably null Het
Tmprss11e A T 5: 86,875,225 (GRCm39) C14S probably benign Het
Tnfrsf14 T C 4: 155,006,934 (GRCm39) probably null Het
Tsfm A C 10: 126,847,512 (GRCm39) V193G probably benign Het
Ube2q2l T A 6: 136,378,371 (GRCm39) Y153F probably benign Het
Ush2a A T 1: 188,175,267 (GRCm39) I1122L probably benign Het
Vmn1r74 T A 7: 11,580,984 (GRCm39) S95T probably damaging Het
Vmn2r98 G A 17: 19,290,015 (GRCm39) C517Y probably damaging Het
Vstm2b G A 7: 40,550,702 (GRCm39) S99N possibly damaging Het
Zbtb24 A G 10: 41,327,537 (GRCm39) N141S probably benign Het
Zcchc4 T G 5: 52,942,512 (GRCm39) C106G 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
R5407:Shh UTSW 5 28,671,578 (GRCm39) nonsense probably null
R6035:Shh UTSW 5 28,666,397 (GRCm39) missense probably damaging 1.00
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 PCR Primer
(F):5'- GCAATGGGTCTCTACCTGAGTC -3'
(R):5'- GATGTGTTCCGTTACCAGCG -3'

Sequencing Primer
(F):5'- CCTCATCCTTAAATATGATGTCGGGG -3'
(R):5'- ATCGGAGACAAGTCCCCTG -3'
Posted On 2016-09-06