Mutagenetix > Incidental Mutation

Incidental Mutation 'D3080:Hyou1'

127

Institutional Source

Beutler Lab

Gene Symbol

Hyou1

Ensembl Gene

ENSMUSG00000032115

Gene Name

hypoxia up-regulated 1

Synonyms

140 kDa, Orp150, Cab140, Grp170, CBP-140

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

D3080 of strain grasshopper

Quality Score

Status

Validated

Chromosome

Chromosomal Location

44290840-44303662 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 44295774 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 343 (V343E)

Ref Sequence

ENSEMBL: ENSMUSP00000123700 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000066601] [ENSMUST00000159473] [ENSMUST00000160902] [ENSMUST00000161318] [ENSMUST00000162560] [ENSMUST00000217019]

AlphaFold

Q9JKR6

Predicted Effect

probably damaging
Transcript: ENSMUST00000066601
AA Change: V343E

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000068594
Gene: ENSMUSG00000032115
AA Change: V343E

Domain	Start	End	E-Value	Type
signal peptide	1	28	N/A	INTRINSIC
Pfam:HSP70	35	669	1.3e-101	PFAM
Pfam:HSP70	690	814	2.1e-6	PFAM
low complexity region	970	986	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000159473

SMART Domains

Protein: ENSMUSP00000124177
Gene: ENSMUSG00000032115

Domain	Start	End	E-Value	Type
signal peptide	1	25	N/A	INTRINSIC
Pfam:HSP70	38	226	2e-37	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000160112

Predicted Effect

probably damaging
Transcript: ENSMUST00000160902
AA Change: V343E

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000125594
Gene: ENSMUSG00000032115
AA Change: V343E

Domain	Start	End	E-Value	Type
signal peptide	1	28	N/A	INTRINSIC
Pfam:HSP70	35	671	3.8e-101	PFAM
Pfam:HSP70	690	814	1.2e-6	PFAM
low complexity region	970	986	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000161318
AA Change: V343E

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000123700
Gene: ENSMUSG00000032115
AA Change: V343E

Domain	Start	End	E-Value	Type
signal peptide	1	28	N/A	INTRINSIC
Pfam:HSP70	35	671	3.8e-101	PFAM
Pfam:HSP70	690	814	1.2e-6	PFAM
low complexity region	970	986	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161537

Predicted Effect

probably benign
Transcript: ENSMUST00000162560

SMART Domains

Protein: ENSMUSP00000123749
Gene: ENSMUSG00000032115

Domain	Start	End	E-Value	Type
signal peptide	1	28	N/A	INTRINSIC
Pfam:HSP70	35	168	6.5e-20	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000217019

Meta Mutation Damage Score

0.9228

Coding Region Coverage

1x: 88.9%
3x: 76.7%

Validation Efficiency

82% (141/173)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the heat shock protein 70 family. This gene uses alternative transcription start sites. A cis-acting segment found in the 5' UTR is involved in stress-dependent induction, resulting in the accumulation of this protein in the endoplasmic reticulum (ER) under hypoxic conditions. The protein encoded by this gene is thought to play an important role in protein folding and secretion in the ER. Since suppression of the protein is associated with accelerated apoptosis, it is also suggested to have an important cytoprotective role in hypoxia-induced cellular perturbation. This protein has been shown to be up-regulated in tumors, especially in breast tumors, and thus it is associated with tumor invasiveness. This gene also has an alternative translation initiation site, resulting in a protein that lacks the N-terminal signal peptide. This signal peptide-lacking protein, which is only 3 amino acids shorter than the mature protein in the ER, is thought to have a housekeeping function in the cytosol. In rat, this protein localizes to both the ER by a carboxy-terminal peptide sequence and to mitochondria by an amino-terminal targeting signal. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
PHENOTYPE: Homozygous null mice display embryonic lethality. Heterozygous mice display increased susceptibility to induced neuronal cell death. [provided by MGI curators]

Allele List at MGI

All alleles(6) : Targeted, knock-out(1) Gene trapped(5)

Other mutations in this stock

Total: 20 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310003L06Rik	C	A	5: 88,119,846 (GRCm39)	P201Q	possibly damaging	Het
Bdp1	A	T	13: 100,160,129 (GRCm39)	S2417R	probably benign	Het
Ccdc168	C	A	1: 44,106,495 (GRCm39)			Het
Dscaml1	A	T	9: 45,595,623 (GRCm39)	H783L	probably benign	Het
Fbxl5	A	T	5: 43,915,708 (GRCm39)	M568K	probably benign	Het
Gab1	T	A	8: 81,493,007 (GRCm39)	D710V	probably damaging	Homo
Gabrr2	T	C	4: 33,084,466 (GRCm39)	F128S	probably damaging	Het
Nlrp4a	A	G	7: 26,143,766 (GRCm39)	T44A	probably benign	Het
Nsd3	C	A	8: 26,203,572 (GRCm39)	T1362N	possibly damaging	Homo
Or6f2	G	A	7: 139,756,275 (GRCm39)	V81M	possibly damaging	Het
Pcm1	T	A	8: 41,728,976 (GRCm39)	N649K	probably damaging	Homo
Pde4dip	T	C	3: 97,674,146 (GRCm39)	K257E	probably damaging	Het
Pfpl	G	A	19: 12,406,196 (GRCm39)	R149Q	probably damaging	Homo
Pou2f2	G	T	7: 24,796,558 (GRCm39)		probably benign	Het
Rptn	A	G	3: 93,303,135 (GRCm39)	D156G	possibly damaging	Het
Sec31a	T	C	5: 100,511,691 (GRCm39)	D1107G	probably damaging	Het
Smyd3	A	G	1: 178,913,987 (GRCm39)	Y239H	probably damaging	Het
Stoml3	T	C	3: 53,405,415 (GRCm39)	F32S	probably benign	Het
Tnnc1	C	A	14: 30,932,147 (GRCm39)	D62E	probably damaging	Homo
Vsig10	C	T	5: 117,481,884 (GRCm39)	A358V	probably damaging	Het

Other mutations in Hyou1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00815:Hyou1	APN	9	44,296,443 (GRCm39)	missense	probably benign	0.02
IGL01660:Hyou1	APN	9	44,292,414 (GRCm39)	missense	possibly damaging	0.75
IGL01677:Hyou1	APN	9	44,293,309 (GRCm39)	missense	probably benign	0.21
IGL01903:Hyou1	APN	9	44,292,438 (GRCm39)	splice site	probably benign
IGL02636:Hyou1	APN	9	44,292,707 (GRCm39)	critical splice donor site	probably null
IGL02806:Hyou1	APN	9	44,300,180 (GRCm39)	nonsense	probably null
IGL03401:Hyou1	APN	9	44,296,206 (GRCm39)	missense	probably damaging	1.00
IGL03410:Hyou1	APN	9	44,299,355 (GRCm39)	missense	probably benign
ANU74:Hyou1	UTSW	9	44,292,560 (GRCm39)	missense	possibly damaging	0.79
PIT4378001:Hyou1	UTSW	9	44,302,148 (GRCm39)	missense	probably benign	0.26
R0408:Hyou1	UTSW	9	44,295,989 (GRCm39)	missense	probably damaging	1.00
R0422:Hyou1	UTSW	9	44,300,539 (GRCm39)	missense	probably damaging	1.00
R1116:Hyou1	UTSW	9	44,295,978 (GRCm39)	missense	probably damaging	1.00
R1581:Hyou1	UTSW	9	44,300,167 (GRCm39)	missense	probably damaging	1.00
R1640:Hyou1	UTSW	9	44,300,703 (GRCm39)	missense	probably benign	0.02
R1803:Hyou1	UTSW	9	44,295,479 (GRCm39)	nonsense	probably null
R2060:Hyou1	UTSW	9	44,292,849 (GRCm39)	missense	probably benign	0.28
R2180:Hyou1	UTSW	9	44,299,316 (GRCm39)	missense	probably benign	0.30
R2233:Hyou1	UTSW	9	44,300,388 (GRCm39)	missense	probably benign	0.44
R2235:Hyou1	UTSW	9	44,300,388 (GRCm39)	missense	probably benign	0.44
R3950:Hyou1	UTSW	9	44,296,524 (GRCm39)	missense	probably damaging	1.00
R4198:Hyou1	UTSW	9	44,300,156 (GRCm39)	missense	probably damaging	1.00
R4200:Hyou1	UTSW	9	44,300,156 (GRCm39)	missense	probably damaging	1.00
R4363:Hyou1	UTSW	9	44,291,912 (GRCm39)	splice site	probably null
R4393:Hyou1	UTSW	9	44,293,169 (GRCm39)	missense	probably damaging	1.00
R4394:Hyou1	UTSW	9	44,293,169 (GRCm39)	missense	probably damaging	1.00
R4812:Hyou1	UTSW	9	44,298,418 (GRCm39)	intron	probably benign
R5239:Hyou1	UTSW	9	44,296,560 (GRCm39)	missense	possibly damaging	0.96
R5648:Hyou1	UTSW	9	44,296,546 (GRCm39)	missense	probably damaging	0.99
R5818:Hyou1	UTSW	9	44,300,223 (GRCm39)	critical splice donor site	probably null
R5856:Hyou1	UTSW	9	44,292,641 (GRCm39)	missense	probably damaging	1.00
R6431:Hyou1	UTSW	9	44,293,322 (GRCm39)	critical splice donor site	probably null
R6594:Hyou1	UTSW	9	44,300,619 (GRCm39)	missense	probably benign
R6596:Hyou1	UTSW	9	44,299,052 (GRCm39)	missense	probably benign	0.00
R6613:Hyou1	UTSW	9	44,293,795 (GRCm39)	missense	probably damaging	0.99
R6704:Hyou1	UTSW	9	44,292,431 (GRCm39)	critical splice donor site	probably null
R6849:Hyou1	UTSW	9	44,298,561 (GRCm39)	missense	probably damaging	0.99
R7494:Hyou1	UTSW	9	44,300,706 (GRCm39)	missense	probably benign	0.04
R7632:Hyou1	UTSW	9	44,292,433 (GRCm39)	splice site	probably null
R7711:Hyou1	UTSW	9	44,295,759 (GRCm39)	missense	possibly damaging	0.91
R8064:Hyou1	UTSW	9	44,296,882 (GRCm39)	missense	possibly damaging	0.80
R8287:Hyou1	UTSW	9	44,299,430 (GRCm39)	missense	probably benign	0.26
R9352:Hyou1	UTSW	9	44,300,926 (GRCm39)	critical splice donor site	probably null
R9385:Hyou1	UTSW	9	44,292,812 (GRCm39)	missense	probably benign	0.06
X0027:Hyou1	UTSW	9	44,302,153 (GRCm39)	missense	possibly damaging	0.89
Z1176:Hyou1	UTSW	9	44,299,039 (GRCm39)	nonsense	probably null

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 1141 of the Hyou1 transcript. The mutated nucleotide causes a valine to glutamic acid substitution at amino acid 343 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Hyou1 gene encodes a 999 amino acid endoplasmic reticulum (ER) protein known as GRP-170 that has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. GRP-170 may play a role as a molecular chaperone and participate in protein folding. GRP-170 is part of a large chaperone multiprotein complex (Uniprot Q9JKR6). Homozygous null mice display embryonic lethality. Heterozygous mice display increased susceptibility to induced neuronal cell death.

The V343E change is predicted to be probably damaging by the PolyPhen program.

Posted On

2010-03-12