Incidental Mutation 'IGL03066:Shh'

• ID: 409690
• Institutional Source: Australian Phenomics Network
• Gene Symbol: Shh
• Ensembl Gene: ENSMUSG00000002633
• Gene Name: sonic hedgehog
• Synonyms: Hhg1
• Essential gene?: Essential (E-score: 1.000)
• Stock #: IGL03066
• Chromosome: 5
• Chromosomal Location: 28661838-28672099 bp(-) (GRCm39)
• Type of Mutation: missense
• DNA Base Change (assembly): G to T at 28666369 bp (GRCm39)
• Zygosity: Heterozygous
• Amino Acid Change: Aspartic acid to Glutamic Acid at position 172 (D172E)
• Ref Sequence: ENSEMBL: ENSMUSP00000002708
• 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: D172E; PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
• SMART Domains: Protein: ENSMUSP00000002708; Gene: ENSMUSG00000002633; AA Change: D172E

Domain	Start	End	E-Value	Type
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: ENSMUST00000180878
• 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]
• Posted On: 2016-08-02