Mutagenetix > Incidental Mutation

Incidental Mutation 'R5454:Htra2'

432664

Institutional Source

Beutler Lab

Gene Symbol

Htra2

Ensembl Gene

ENSMUSG00000068329

Gene Name

HtrA serine peptidase 2

Synonyms

Prss25, HtrA2, mnd2, OMI

MMRRC Submission

043018-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5454 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

83028247-83031552 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 83030995 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Leucine at position 138 (P138L)

Ref Sequence

ENSEMBL: ENSMUSP00000109595 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000000707] [ENSMUST00000077502] [ENSMUST00000089645] [ENSMUST00000092618] [ENSMUST00000101257] [ENSMUST00000113962] [ENSMUST00000113963] [ENSMUST00000122955] [ENSMUST00000134606] [ENSMUST00000204803]

AlphaFold

Q9JIY5

Predicted Effect

probably benign
Transcript: ENSMUST00000000707

SMART Domains

Protein: ENSMUSP00000000707
Gene: ENSMUSG00000000693

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
SR	45	146	2.1e-50	SMART
SR	170	283	1.09e-25	SMART
SR	308	408	3.72e-51	SMART
SR	418	526	8.5e-37	SMART
Pfam:Lysyl_oxidase	530	730	3.9e-103	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000077502

SMART Domains

Protein: ENSMUSP00000076708
Gene: ENSMUSG00000009145

Domain	Start	End	E-Value	Type
low complexity region	2	19	N/A	INTRINSIC
DEXDc	30	236	5.01e-4	SMART
low complexity region	268	280	N/A	INTRINSIC
low complexity region	288	301	N/A	INTRINSIC
HA2	441	530	4e-19	SMART
Pfam:OB_NTP_bind	555	674	2.2e-11	PFAM
low complexity region	695	708	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000089645
AA Change: P138L

PolyPhen 2 Score 0.488 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000087073
Gene: ENSMUSG00000068329
AA Change: P138L

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
transmembrane domain	106	125	N/A	INTRINSIC
low complexity region	128	143	N/A	INTRINSIC
Pfam:Trypsin	170	341	1.1e-14	PFAM
Pfam:Trypsin_2	182	320	1.2e-34	PFAM
PDZ	371	445	2.86e-10	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000092618

SMART Domains

Protein: ENSMUSP00000090281
Gene: ENSMUSG00000068328

Domain	Start	End	E-Value	Type
low complexity region	10	40	N/A	INTRINSIC
transmembrane domain	52	74	N/A	INTRINSIC
PlsC	119	222	1.04e-1	SMART
low complexity region	307	322	N/A	INTRINSIC
CUE	325	366	1.3e-9	SMART
low complexity region	378	392	N/A	INTRINSIC
low complexity region	421	439	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000101257

SMART Domains

Protein: ENSMUSP00000098815
Gene: ENSMUSG00000000693

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
SR	45	146	2.1e-50	SMART
SR	170	283	1.09e-25	SMART
SR	308	396	5.46e-17	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000113962
AA Change: P138L

PolyPhen 2 Score 0.958 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000109595
Gene: ENSMUSG00000068329
AA Change: P138L

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
transmembrane domain	106	125	N/A	INTRINSIC
low complexity region	128	143	N/A	INTRINSIC
Pfam:Trypsin_2	182	237	2.7e-12	PFAM
Pfam:Trypsin	212	277	4.5e-6	PFAM
PDZ	285	348	4.89e-1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000113963
AA Change: P138L

PolyPhen 2 Score 0.428 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000109596
Gene: ENSMUSG00000068329
AA Change: P138L

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
transmembrane domain	106	125	N/A	INTRINSIC
low complexity region	128	143	N/A	INTRINSIC
Pfam:Trypsin	170	342	6.8e-15	PFAM
Pfam:Trypsin_2	182	320	7.1e-24	PFAM
PDZ	350	413	4.89e-1	SMART

Predicted Effect

unknown
Transcript: ENSMUST00000150217
AA Change: P8L

SMART Domains

Protein: ENSMUSP00000118234
Gene: ENSMUSG00000068329
AA Change: P8L

Domain	Start	End	E-Value	Type
low complexity region	4	11	N/A	INTRINSIC
Pfam:Trypsin	41	215	1.6e-11	PFAM
Pfam:Trypsin_2	53	190	1.8e-31	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000122955
AA Change: P138L

PolyPhen 2 Score 0.871 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000138153
Gene: ENSMUSG00000068329
AA Change: P138L

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
transmembrane domain	106	125	N/A	INTRINSIC
low complexity region	128	143	N/A	INTRINSIC
Pfam:Trypsin	170	321	2.1e-10	PFAM
Pfam:Trypsin_2	182	317	9.5e-21	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000203915

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144058

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203749

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184661

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203339

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155502

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203180

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203331

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203123

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154829

Predicted Effect

probably benign
Transcript: ENSMUST00000132099

Predicted Effect

probably benign
Transcript: ENSMUST00000134606

SMART Domains

Protein: ENSMUSP00000115547
Gene: ENSMUSG00000068329

Domain	Start	End	E-Value	Type
Pfam:Trypsin	7	180	2.7e-15	PFAM
Pfam:Trypsin_2	20	158	3.1e-24	PFAM
PDZ	209	283	2.86e-10	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000204719

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204761

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204895

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204510

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000205042

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204385

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204752

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000205152

Predicted Effect

probably benign
Transcript: ENSMUST00000204803

SMART Domains

Protein: ENSMUSP00000144697
Gene: ENSMUSG00000009145

Domain	Start	End	E-Value	Type
low complexity region	2	19	N/A	INTRINSIC
DEXDc	30	236	2.1e-6	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204383

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204281

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204209

Predicted Effect

probably benign
Transcript: ENSMUST00000204343

Meta Mutation Damage Score

0.1062

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.2%
20x: 95.1%

Validation Efficiency

100% (60/60)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
PHENOTYPE: Homozygous mutations of this gene cause progressive parkinsonian symptoms, loss of striatal neurons, spleen and thymus atrophy, failure to thrive, and death before 40 days of age. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930579C12Rik	T	C	9: 89,051,041 (GRCm39)		noncoding transcript	Het
Ankfy1	A	T	11: 72,637,757 (GRCm39)	H483L	probably benign	Het
Ankrd46	C	T	15: 36,479,447 (GRCm39)	G215R	probably damaging	Het
Apobec1	T	C	6: 122,558,327 (GRCm39)	I143V	probably benign	Het
Atp2b4	C	A	1: 133,657,610 (GRCm39)	V627F	probably damaging	Het
Ccdc80	T	A	16: 44,947,588 (GRCm39)	Y855*	probably null	Het
Cd209b	T	C	8: 3,975,396 (GRCm39)	E88G	probably damaging	Het
Ceacam14	T	G	7: 17,548,110 (GRCm39)	W67G	probably damaging	Het
Cope	T	C	8: 70,757,306 (GRCm39)	V50A	probably benign	Het
Dcaf13	C	A	15: 38,987,759 (GRCm39)	D168E	probably benign	Het
Dhcr7	T	G	7: 143,391,576 (GRCm39)	M55R	probably damaging	Het
Enpp7	A	T	11: 118,879,634 (GRCm39)	Y96F	probably benign	Het
Esco1	T	C	18: 10,584,327 (GRCm39)	D60G	probably benign	Het
Fgfr3	G	A	5: 33,880,642 (GRCm39)		probably benign	Het
Frzb	T	C	2: 80,248,259 (GRCm39)	D280G	probably damaging	Het
Gcat	A	G	15: 78,920,610 (GRCm39)	I317V	probably benign	Het
Gm13030	A	T	4: 138,600,820 (GRCm39)		probably benign	Het
Gmds	A	G	13: 32,312,024 (GRCm39)	L135P	probably damaging	Het
Il5	A	G	11: 53,614,626 (GRCm39)	N89S	probably damaging	Het
Ints3	G	A	3: 90,315,834 (GRCm39)	T310M	possibly damaging	Het
Itih2	T	C	2: 10,102,804 (GRCm39)	I777V	probably null	Het
Kctd9	T	C	14: 67,977,836 (GRCm39)	L382S	probably damaging	Het
Loricrin	A	G	3: 91,988,789 (GRCm39)	S166P	unknown	Het
Mga	T	A	2: 119,733,810 (GRCm39)	N219K	probably damaging	Het
Mtmr4	A	T	11: 87,501,868 (GRCm39)	R641*	probably null	Het
Muc6	C	T	7: 141,235,078 (GRCm39)	A611T	possibly damaging	Het
Obox3-ps8	A	T	17: 36,763,903 (GRCm39)		noncoding transcript	Het
Or5p54	A	T	7: 107,554,096 (GRCm39)	M83L	probably benign	Het
Otud4	C	T	8: 80,377,671 (GRCm39)	L111F	possibly damaging	Het
Pcdhga12	T	A	18: 37,899,314 (GRCm39)	S49T	possibly damaging	Het
Pcdhgc3	A	G	18: 37,941,549 (GRCm39)	D650G	probably damaging	Het
Pcmt1	A	G	10: 7,516,509 (GRCm39)	V167A	probably damaging	Het
Pcnt	A	T	10: 76,225,381 (GRCm39)		probably null	Het
Pcx	G	T	19: 4,652,504 (GRCm39)	V164F	probably damaging	Het
Plekhg4	T	C	8: 106,102,745 (GRCm39)		probably null	Het
Pmch	A	G	10: 87,927,707 (GRCm39)	E136G	probably damaging	Het
Prkar1a	A	G	11: 109,550,886 (GRCm39)	D80G	probably benign	Het
Ryr3	T	C	2: 112,560,647 (GRCm39)		probably null	Het
Slc10a7	T	C	8: 79,413,253 (GRCm39)	S171P	possibly damaging	Het
Sox6	A	T	7: 115,301,008 (GRCm39)	M153K	possibly damaging	Het
Srgap2	T	C	1: 131,217,475 (GRCm39)	I946V	probably benign	Het
Strbp	T	C	2: 37,535,495 (GRCm39)	E71G	probably benign	Het
Synpo2l	C	A	14: 20,712,360 (GRCm39)	A87S	probably damaging	Het
Tnrc18	T	C	5: 142,757,446 (GRCm39)	D1025G	unknown	Het
Tnxb	A	G	17: 34,928,599 (GRCm39)	H2671R	possibly damaging	Het
Tor1b	GGACG	GG	2: 30,846,957 (GRCm39)		probably benign	Het
Umodl1	A	T	17: 31,205,439 (GRCm39)	D649V	possibly damaging	Het
Usp13	G	T	3: 32,959,585 (GRCm39)	A559S	probably damaging	Het
Vps45	G	A	3: 95,926,969 (GRCm39)	P526L	probably benign	Het
Zfp687	A	G	3: 94,916,457 (GRCm39)	V855A	probably damaging	Het
Zfp771	T	A	7: 126,853,448 (GRCm39)	C205S	probably damaging	Het

Other mutations in Htra2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01466:Htra2	APN	6	83,031,304 (GRCm39)	missense	probably damaging	1.00
IGL02392:Htra2	APN	6	83,031,280 (GRCm39)	missense	possibly damaging	0.78
IGL02510:Htra2	APN	6	83,028,592 (GRCm39)	missense	probably damaging	0.98
IGL03324:Htra2	APN	6	83,030,737 (GRCm39)	missense	probably damaging	1.00
R1813:Htra2	UTSW	6	83,028,583 (GRCm39)	missense	probably damaging	0.99
R4791:Htra2	UTSW	6	83,028,798 (GRCm39)	missense	probably damaging	1.00
R5185:Htra2	UTSW	6	83,031,223 (GRCm39)	missense	probably benign	0.14
R6364:Htra2	UTSW	6	83,030,027 (GRCm39)	missense	probably damaging	1.00
R6853:Htra2	UTSW	6	83,030,812 (GRCm39)	unclassified	probably benign
R7259:Htra2	UTSW	6	83,028,520 (GRCm39)	missense	possibly damaging	0.81
R7939:Htra2	UTSW	6	83,028,545 (GRCm39)	missense	probably damaging	1.00
Z1176:Htra2	UTSW	6	83,031,364 (GRCm39)	missense	probably benign	0.08
Z1177:Htra2	UTSW	6	83,030,737 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CGTTTGAGATGGGGACTTCACG -3'
(R):5'- GCACGATTGAATGTGGGGAC -3'

Sequencing Primer
(F):5'- AGTACCCATTACACTGCAGCTTC -3'
(R):5'- ACTTCAGGCTCCAGTGACCAG -3'

Posted On

2016-10-06