Incidental Mutation 'R8682:Shh'
ID 661796
Institutional Source Beutler Lab
Gene Symbol Shh
Ensembl Gene ENSMUSG00000002633
Gene Name sonic hedgehog
Synonyms Hhg1
MMRRC Submission 068537-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R8682 (G1)
Quality Score 92.0077
Status Not validated
Chromosome 5
Chromosomal Location 28661838-28672099 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 28663058 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Leucine at position 370 (H370L)
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 benign
Transcript: ENSMUST00000002708
AA Change: H370L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000002708
Gene: ENSMUSG00000002633
AA Change: H370L

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: 99.9%
  • 3x: 99.8%
  • 10x: 98.9%
  • 20x: 95.7%
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: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810065E05Rik T A 11: 58,314,725 (GRCm39) L141Q probably null Het
Abtb2 A T 2: 103,397,720 (GRCm39) T217S probably benign Het
Adcy1 T C 11: 7,111,328 (GRCm39) I873T probably damaging Het
Angpt4 A G 2: 151,769,005 (GRCm39) M172V probably benign Het
Apaf1 A T 10: 90,831,532 (GRCm39) V1194D probably damaging Het
Arhgap30 T C 1: 171,234,970 (GRCm39) S479P probably benign Het
Asah2 C T 19: 32,030,277 (GRCm39) V132M probably damaging Het
Bmp10 A G 6: 87,410,541 (GRCm39) probably null Het
Bsn T C 9: 107,983,368 (GRCm39) Y790C Het
Cacna2d1 C A 5: 16,558,837 (GRCm39) R732S possibly damaging Het
Casr A T 16: 36,315,784 (GRCm39) F762Y possibly damaging Het
Cbln1 T C 8: 88,198,735 (GRCm39) D45G possibly damaging Het
Cd177 A T 7: 24,459,438 (GRCm39) M61K possibly damaging Het
Cdh11 T C 8: 103,377,348 (GRCm39) I433V probably benign Het
Cdhr5 A G 7: 140,855,899 (GRCm39) probably null Het
Col12a1 T A 9: 79,568,358 (GRCm39) K1622I probably benign Het
Cyp2d9 A G 15: 82,337,917 (GRCm39) D103G probably damaging Het
Dync2i1 A T 12: 116,188,610 (GRCm39) H661Q probably damaging Het
Eif4a3l1 A G 6: 136,306,027 (GRCm39) T163A possibly damaging Het
Fem1b A T 9: 62,704,432 (GRCm39) L276* probably null Het
Fggy T A 4: 95,700,358 (GRCm39) V343E probably damaging Het
Flt3 A G 5: 147,320,265 (GRCm39) V33A probably benign Het
Grn T C 11: 102,325,646 (GRCm39) Y288H probably benign Het
Grtp1 G A 8: 13,229,499 (GRCm39) R272W probably damaging Het
H2-Aa A G 17: 34,502,734 (GRCm39) I144T possibly damaging Het
Herc1 A G 9: 66,370,130 (GRCm39) D469G Het
Hsf2 G A 10: 57,381,267 (GRCm39) E286K possibly damaging Het
Hydin A G 8: 111,035,798 (GRCm39) E163G probably damaging Het
Il6ra A G 3: 89,793,976 (GRCm39) I224T possibly damaging Het
Itih3 T A 14: 30,642,673 (GRCm39) I204F possibly damaging Het
Kcnj9 A T 1: 172,153,680 (GRCm39) M148K possibly damaging Het
Lepr T G 4: 101,649,269 (GRCm39) V890G probably benign Het
Mslnl A G 17: 25,965,962 (GRCm39) D612G probably benign Het
Myl2 T A 5: 122,244,798 (GRCm39) V156D probably damaging Het
Neb C A 2: 52,136,857 (GRCm39) W3208L probably damaging Het
Neto2 T C 8: 86,367,295 (GRCm39) Y511C probably benign Het
Obi1 G T 14: 104,717,669 (GRCm39) R235S probably damaging Het
Obox2 C A 7: 15,130,912 (GRCm39) T48K possibly damaging Het
Or14a259 C T 7: 86,013,373 (GRCm39) M57I probably damaging Het
Or51f2 T A 7: 102,526,646 (GRCm39) F106L probably benign Het
Or5aq6 A T 2: 86,923,390 (GRCm39) M117K possibly damaging Het
Osbpl6 C G 2: 76,407,425 (GRCm39) H486D probably benign Het
Pfkfb3 T C 2: 11,489,144 (GRCm39) K264E probably benign Het
Phf11 G A 14: 59,496,033 (GRCm39) T27I probably benign Het
Pla2r1 T A 2: 60,253,120 (GRCm39) T1324S possibly damaging Het
Plekhg1 A T 10: 3,897,523 (GRCm39) Y495F Het
Ppp2r5d T C 17: 46,997,989 (GRCm39) K225E probably benign Het
Ptpn11 T C 5: 121,306,053 (GRCm39) D64G possibly damaging Het
Ptprs A G 17: 56,742,849 (GRCm39) I431T probably damaging Het
Rapgef5 T C 12: 117,545,432 (GRCm39) S100P probably benign Het
Siah3 A T 14: 75,763,043 (GRCm39) H98L possibly damaging Het
Sim2 C T 16: 93,924,192 (GRCm39) H446Y probably benign Het
Skint4 T C 4: 111,993,237 (GRCm39) I320T possibly damaging Het
Sorcs1 A T 19: 50,367,398 (GRCm39) N221K probably damaging Het
Sox6 T C 7: 115,076,191 (GRCm39) S816G probably damaging Het
Sphkap T C 1: 83,256,997 (GRCm39) T251A probably benign Het
Stard9 T C 2: 120,533,796 (GRCm39) V3351A possibly damaging Het
Tbc1d15 A G 10: 115,046,195 (GRCm39) V436A probably benign Het
Thsd7b A T 1: 129,688,011 (GRCm39) K641* probably null Het
Tmc5 G T 7: 118,269,925 (GRCm39) V892F possibly damaging Het
Tpsab1 T A 17: 25,562,685 (GRCm39) H238L probably benign Het
Trank1 A G 9: 111,194,412 (GRCm39) N812S probably benign Het
Trio T A 15: 27,905,278 (GRCm39) N163Y unknown Het
Ttc39d A G 17: 80,524,693 (GRCm39) T451A probably benign Het
Ube3b T C 5: 114,550,351 (GRCm39) L832P probably damaging Het
Vmn2r15 C A 5: 109,441,938 (GRCm39) C165F probably damaging Het
Vmn2r90 T C 17: 17,932,344 (GRCm39) F84L possibly damaging Het
Wdr95 C T 5: 149,518,752 (GRCm39) T531I possibly damaging Het
Zcrb1 C A 15: 93,284,118 (GRCm39) G191V probably benign Het
Zfp111 G A 7: 23,897,983 (GRCm39) P544S probably damaging Het
Zfyve9 T C 4: 108,576,539 (GRCm39) S181G 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
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
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'- CATTCCCAAGGGATGCATGGTC -3'
(R):5'- TCTACGTGATCGAGACGCTG -3'

Sequencing Primer
(F):5'- GATGCATGGTCTCGCTGTCC -3'
(R):5'- TACGTGGTGGCTGAACGC -3'
Posted On 2021-03-08