Incidental Mutation 'R9300:Shh'
ID 704842
Institutional Source Beutler Lab
Gene Symbol Shh
Ensembl Gene ENSMUSG00000002633
Gene Name sonic hedgehog
Synonyms Hhg1
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9300 (G1)
Quality Score 163.009
Status Not validated
Chromosome 5
Chromosomal Location 28661838-28672099 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 28663461 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 236 (Y236H)
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: Y236H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000002708
Gene: ENSMUSG00000002633
AA Change: Y236H

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
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: 88 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb1b G A 5: 8,875,614 (GRCm39) V596I probably benign Het
Acad8 A T 9: 26,888,928 (GRCm39) H371Q probably damaging Het
Actn3 G T 19: 4,921,656 (GRCm39) R175S probably benign Het
Adamts9 G T 6: 92,864,371 (GRCm39) D780E probably benign Het
AK157302 C A 13: 21,679,537 (GRCm39) T21K probably benign Het
Ank3 A T 10: 69,706,872 (GRCm39) H329L unknown Het
Ankrd36 A G 11: 5,519,979 (GRCm39) H18R possibly damaging Het
Anks1b T A 10: 90,412,966 (GRCm39) V38D possibly damaging Het
Apbb2 A T 5: 66,470,677 (GRCm39) L520H probably damaging Het
Arid1b C A 17: 5,293,274 (GRCm39) P731T probably damaging Het
Atp1a4 A G 1: 172,067,398 (GRCm39) F578S probably damaging Het
Atp6v0a2 A T 5: 124,789,312 (GRCm39) I360F probably damaging Het
Bcas3 A T 11: 85,448,184 (GRCm39) I600F probably damaging Het
C1qtnf7 T G 5: 43,766,441 (GRCm39) C20W possibly damaging Het
Cadm1 A T 9: 47,708,821 (GRCm39) K184* probably null Het
Ccdc138 A T 10: 58,343,448 (GRCm39) H101L probably benign Het
Cep120 T A 18: 53,852,369 (GRCm39) N503I probably damaging Het
Chil4 T C 3: 106,109,874 (GRCm39) T380A probably benign Het
Clip2 A G 5: 134,526,942 (GRCm39) probably null Het
Cyp3a11 G A 5: 145,799,164 (GRCm39) P341L possibly damaging Het
Cyp3a41a G C 5: 145,656,906 (GRCm39) probably benign Het
Dcaf1 A G 9: 106,725,042 (GRCm39) I509M possibly damaging Het
Dcaf13 T C 15: 39,010,102 (GRCm39) S429P probably damaging Het
Eln A G 5: 134,758,220 (GRCm39) V151A unknown Het
Endou T G 15: 97,610,954 (GRCm39) M377L probably benign Het
Etfa A G 9: 55,396,152 (GRCm39) I138T probably damaging Het
Fbxw10 T A 11: 62,768,109 (GRCm39) S982T probably benign Het
Gm9602 A T 14: 15,933,435 (GRCm39) R47* probably null Het
Hectd4 G A 5: 121,486,952 (GRCm39) V3316I probably benign Het
Hif1a T C 12: 73,987,302 (GRCm39) L477S probably benign Het
Icam5 G C 9: 20,946,846 (GRCm39) G458A probably benign Het
Itm2b A T 14: 73,603,896 (GRCm39) D106E probably benign Het
Kdm4d G A 9: 14,375,336 (GRCm39) T174M probably damaging Het
Kif16b G T 2: 142,541,207 (GRCm39) D1364E probably benign Het
Lbhd1 G A 19: 8,861,550 (GRCm39) V61M probably damaging Het
Lclat1 T A 17: 73,546,919 (GRCm39) S279T probably benign Het
Lhx4 G A 1: 155,580,956 (GRCm39) L190F probably damaging Het
Lima1 C T 15: 99,704,320 (GRCm39) S283N probably benign Het
Magi1 C A 6: 93,724,209 (GRCm39) D496Y probably damaging Het
Map1a T C 2: 121,133,446 (GRCm39) S1421P probably damaging Het
Map3k20 C T 2: 72,202,257 (GRCm39) H163Y probably damaging Het
Mier3 T G 13: 111,822,890 (GRCm39) probably null Het
Mllt3 G A 4: 87,692,284 (GRCm39) Q560* probably null Het
Mmp25 T A 17: 23,851,728 (GRCm39) D327V probably benign Het
Nckap5 G A 1: 125,909,423 (GRCm39) Q1603* probably null Het
Nell1 G A 7: 49,712,368 (GRCm39) V63I probably benign Het
Or10al3 C T 17: 38,011,815 (GRCm39) P85S probably damaging Het
Or2ag2b A T 7: 106,418,111 (GRCm39) I274F probably benign Het
Or8a1 A C 9: 37,641,578 (GRCm39) S234A probably benign Het
Pde12 C T 14: 26,386,931 (GRCm39) E526K probably damaging Het
Pfn4 T C 12: 4,825,442 (GRCm39) V93A possibly damaging Het
Poglut2 A G 1: 44,156,362 (GRCm39) I75T possibly damaging Het
Ppp2r3d A G 9: 124,423,977 (GRCm38) S60P unknown Het
Prelp T C 1: 133,842,257 (GRCm39) H296R probably damaging Het
Prickle1 T C 15: 93,398,749 (GRCm39) E693G possibly damaging Het
Rars1 A G 11: 35,706,488 (GRCm39) L477P probably damaging Het
Rasal1 G A 5: 120,802,172 (GRCm39) R328H probably damaging Het
Rasef A G 4: 73,659,393 (GRCm39) F220S probably benign Het
Rif1 C T 2: 52,001,151 (GRCm39) S1535L probably damaging Het
Rnf17 T C 14: 56,697,495 (GRCm39) I463T possibly damaging Het
Ryr3 A T 2: 112,690,695 (GRCm39) D1138E probably benign Het
Scn9a T A 2: 66,335,236 (GRCm39) Y1251F probably benign Het
Sdk2 A G 11: 113,715,856 (GRCm39) W1568R possibly damaging Het
Senp6 A G 9: 80,049,433 (GRCm39) E1019G probably damaging Het
Sin3a A G 9: 57,014,744 (GRCm39) D655G probably damaging Het
Slc35a4 C T 18: 36,815,274 (GRCm39) P35S probably damaging Het
Slc35g1 T C 19: 38,384,633 (GRCm39) L24P probably benign Het
Slc39a4 G T 15: 76,498,759 (GRCm39) Q312K probably damaging Het
Slc6a5 A T 7: 49,601,175 (GRCm39) I659F probably damaging Het
Slc7a4 T C 16: 17,392,399 (GRCm39) Y345C probably benign Het
Slco6c1 G T 1: 96,993,809 (GRCm39) R645S probably benign Het
Soat1 T C 1: 156,268,923 (GRCm39) Y209C probably benign Het
Tbc1d9b T C 11: 50,054,714 (GRCm39) S953P probably benign Het
Tgm1 G A 14: 55,942,303 (GRCm39) H683Y probably benign Het
Tmem98 G A 11: 80,708,432 (GRCm39) R134Q probably damaging Het
Trpm3 A C 19: 22,955,745 (GRCm39) M1107L possibly damaging Het
Vmn1r11 G A 6: 57,114,872 (GRCm39) V179I probably benign Het
Vmn1r119 G T 7: 20,745,638 (GRCm39) T248K probably damaging Het
Vmn1r236 T A 17: 21,506,945 (GRCm39) I21N possibly damaging Het
Vmn2r24 A G 6: 123,793,030 (GRCm39) T786A possibly damaging Het
Vstm5 A T 9: 15,168,585 (GRCm39) I50F probably damaging Het
Wdr1 T C 5: 38,685,255 (GRCm39) D572G probably damaging Het
Xaf1 T C 11: 72,192,517 (GRCm39) F5S probably benign Het
Zan A T 5: 137,468,519 (GRCm39) probably null Het
Zfp697 T C 3: 98,334,979 (GRCm39) V248A possibly damaging Het
Zftraf1 C A 15: 76,530,541 (GRCm39) V260L probably benign Het
Zkscan3 T A 13: 21,577,667 (GRCm39) T249S unknown Het
Znfx1 A G 2: 166,897,860 (GRCm39) Y355H probably damaging 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
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
X0019:Shh UTSW 5 28,666,538 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TGATGAGAATGGTGCCGTGC -3'
(R):5'- TTTGGCACTCAACACCTGGTC -3'

Sequencing Primer
(F):5'- GCGTTCAGCCACCACGTAC -3'
(R):5'- GGTCTTTCTCTCTACTCCGCAGAG -3'
Posted On 2022-03-25