Mutagenetix > Incidental Mutation

Incidental Mutation 'R4153:Shh'

368381

Institutional Source

Beutler Lab

Gene Symbol

Shh

Ensembl Gene

ENSMUSG00000002633

Gene Name

sonic hedgehog

Synonyms

Hhg1

MMRRC Submission

040997-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4153 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

28661838-28672099 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 28662947 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 407 (I407N)

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: I407N

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000002708
Gene: ENSMUSG00000002633
AA Change: I407N

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

Meta Mutation Damage Score

0.6870

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.7%

Validation Efficiency

96% (53/55)

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: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2210408I21Rik	T	C	13: 77,341,292 (GRCm39)	V47A	probably benign	Het
4932414N04Rik	A	T	2: 68,498,941 (GRCm39)		probably benign	Het
Acat2	T	A	17: 13,171,153 (GRCm39)	H159L	possibly damaging	Het
Acsl5	A	G	19: 55,269,895 (GRCm39)	E253G	probably benign	Het
Adam34l	T	A	8: 44,079,564 (GRCm39)	Y220F	probably benign	Het
Ddx41	G	A	13: 55,682,293 (GRCm39)	R205W	possibly damaging	Het
Ebf2	T	G	14: 67,472,672 (GRCm39)	V30G	probably damaging	Het
Erlin1	T	A	19: 44,056,056 (GRCm39)	T60S	probably benign	Het
Fanca	A	G	8: 124,031,617 (GRCm39)	V358A	possibly damaging	Het
Fastkd3	T	C	13: 68,738,257 (GRCm39)	F602S	probably damaging	Het
Fras1	C	A	5: 96,924,594 (GRCm39)	N3678K	probably benign	Het
Gopc	T	C	10: 52,225,239 (GRCm39)	I277V	probably damaging	Het
Gpd2	A	G	2: 57,245,783 (GRCm39)	T438A	probably damaging	Het
Gzma	T	C	13: 113,232,802 (GRCm39)	K97E	possibly damaging	Het
Gzmn	T	A	14: 56,405,299 (GRCm39)	T62S	probably damaging	Het
Hip1	T	C	5: 135,441,560 (GRCm39)	E570G	probably damaging	Het
Hs3st6	T	C	17: 24,977,339 (GRCm39)	V273A	possibly damaging	Het
Jarid2	C	A	13: 45,063,902 (GRCm39)	S873R	probably damaging	Het
Klk14	G	A	7: 43,341,501 (GRCm39)	C51Y	probably damaging	Het
Mast2	T	C	4: 116,173,160 (GRCm39)	N548S	possibly damaging	Het
Mthfr	G	T	4: 148,135,932 (GRCm39)	R335L	probably damaging	Het
Ndst3	T	C	3: 123,465,876 (GRCm39)	Y32C	probably damaging	Het
Nwd1	T	C	8: 73,408,564 (GRCm39)	L808P	probably damaging	Het
Or52b1	T	C	7: 104,978,592 (GRCm39)	N269S	probably damaging	Het
Or56a3b	A	T	7: 104,771,516 (GRCm39)	H284L	probably damaging	Het
Or8g52	A	C	9: 39,631,296 (GRCm39)	M258L	probably benign	Het
Pgk2	A	G	17: 40,519,149 (GRCm39)	V93A	probably damaging	Het
Pigk	G	A	3: 152,445,766 (GRCm39)	V126I	probably damaging	Het
Plcl2	A	T	17: 50,913,389 (GRCm39)	K133*	probably null	Het
Pofut2	A	G	10: 77,104,500 (GRCm39)	K426E	probably benign	Het
Rbpj	T	A	5: 53,806,789 (GRCm39)	H230Q	probably damaging	Het
Rnf213	A	G	11: 119,300,308 (GRCm39)	K269E	probably benign	Het
Sntg1	A	T	1: 8,653,569 (GRCm39)		probably null	Het
Svep1	A	T	4: 58,089,426 (GRCm39)	F1661Y	possibly damaging	Het
Tep1	G	A	14: 51,075,051 (GRCm39)	H1755Y	possibly damaging	Het
Thrap3	A	C	4: 126,067,235 (GRCm39)		probably null	Het
Thumpd1	C	T	7: 119,319,816 (GRCm39)	C50Y	probably damaging	Het
Tmem131	T	C	1: 36,847,874 (GRCm39)		probably benign	Het
Tnrc18	T	C	5: 142,751,747 (GRCm39)	D1368G	possibly damaging	Het
Tubd1	G	A	11: 86,440,296 (GRCm39)	G107S	probably damaging	Het
Ugt1a6a	A	G	1: 88,066,193 (GRCm39)		probably null	Het
Uty	A	G	Y: 1,158,327 (GRCm39)	V572A	possibly damaging	Het
Vmn1r171	A	G	7: 23,332,077 (GRCm39)	K89E	probably damaging	Het
Vmn2r100	AAAACAGGAGTATTGATTGGAAAC	AAAAC	17: 19,743,681 (GRCm39)		probably null	Het
Vmn2r106	A	G	17: 20,488,080 (GRCm39)	L773P	probably damaging	Het
Vps13b	T	A	15: 35,792,173 (GRCm39)		probably null	Het

Other mutations in Shh

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- AGTCTACTTTGGACTGCCCTAC -3'
(R):5'- CATTCTCATCAACCGGGTGCTC -3'

Sequencing Primer
(F):5'- AATTAAAAGTCTCCTTCCGTGCG -3'
(R):5'- GTGCTCGCCTCGTGCTAC -3'

Posted On

2016-02-03