|Institutional Source||Beutler Lab|
|Gene Name||sonic hedgehog|
|Synonyms||Hx, Hxl3, Hhg1, M100081|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R7650 (G1)|
|Chromosomal Location||28456815-28467256 bp(-) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||C to A at 28458306 bp|
|Amino Acid Change||Serine to Isoleucine at position 288 (S288I)|
|Ref Sequence||ENSEMBL: ENSMUSP00000002708 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000002708]|
|Predicted Effect||probably benign
AA Change: S288I
PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
AA Change: S288I
|Meta Mutation Damage Score||0.0898|
|Coding Region Coverage||
|Validation Efficiency||100% (80/80)|
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||
|Other mutations in Shh||
(F):5'- CGGTTGATGAGAATGGTGCC -3'
(R):5'- TCTCTACTCCGCAGAGAACTC -3'
(F):5'- ATGAGAATGGTGCCGTGCG -3'
(R):5'- AAATCCGGCGGCTGTTTC -3'