Mutagenetix > Incidental Mutation

Incidental Mutation 'R1813:Htra2'

202543

Institutional Source

Beutler Lab

Gene Symbol

Htra2

Ensembl Gene

ENSMUSG00000068329

Gene Name

HtrA serine peptidase 2

Synonyms

Prss25, HtrA2, mnd2, OMI

MMRRC Submission

039841-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1813 (G1)

Quality Score

224

Status

Validated

Chromosome

Chromosomal Location

83028247-83031552 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 83028583 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Aspartic acid at position 318 (A318D)

Ref Sequence

ENSEMBL: ENSMUSP00000109595 (fasta)

Gene Model

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

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

possibly damaging
Transcript: ENSMUST00000089645
AA Change: A415D

PolyPhen 2 Score 0.924 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000087073
Gene: ENSMUSG00000068329
AA Change: A415D

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: A318D

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000109595
Gene: ENSMUSG00000068329
AA Change: A318D

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

possibly damaging
Transcript: ENSMUST00000113963
AA Change: A383D

PolyPhen 2 Score 0.700 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000109596
Gene: ENSMUSG00000068329
AA Change: A383D

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

probably benign
Transcript: ENSMUST00000122955

SMART Domains

Protein: ENSMUSP00000138153
Gene: ENSMUSG00000068329

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: ENSMUST00000134606
AA Change: A253D

PolyPhen 2 Score 0.052 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000115547
Gene: ENSMUSG00000068329
AA Change: A253D

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: ENSMUST00000204343

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154829

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203339

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203180

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203331

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204281

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155502

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184661

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204209

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144058

Predicted Effect

probably benign
Transcript: ENSMUST00000203915

Predicted Effect

probably benign
Transcript: ENSMUST00000132099

Predicted Effect

probably benign
Transcript: ENSMUST00000150217

SMART Domains

Protein: ENSMUSP00000118234
Gene: ENSMUSG00000068329

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

noncoding transcript
Transcript: ENSMUST00000204895

Predicted Effect

probably benign
Transcript: ENSMUST00000204719

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204761

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000205042

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204383

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204510

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204385

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000205152

Meta Mutation Damage Score

0.2047

Coding Region Coverage

1x: 97.5%
3x: 96.8%
10x: 94.8%
20x: 90.3%

Validation Efficiency

96% (79/82)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2ml1	T	A	6: 128,543,236 (GRCm39)	N595Y	probably benign	Het
Abca6	A	G	11: 110,124,671 (GRCm39)		probably benign	Het
Abo	C	A	2: 26,733,609 (GRCm39)	D199Y	probably damaging	Het
Acvr1c	A	C	2: 58,170,306 (GRCm39)	V277G	probably damaging	Het
Adam23	G	A	1: 63,584,731 (GRCm39)	A380T	probably benign	Het
Art2b	A	G	7: 101,229,236 (GRCm39)	V221A	probably benign	Het
Bcam	A	G	7: 19,500,640 (GRCm39)	S153P	probably damaging	Het
Brip1	T	C	11: 86,077,906 (GRCm39)	H174R	possibly damaging	Het
Ccdc186	T	C	19: 56,788,601 (GRCm39)	D536G	probably benign	Het
Cd109	A	G	9: 78,524,287 (GRCm39)	N67S	probably benign	Het
Cd8a	G	T	6: 71,350,947 (GRCm39)	M137I	possibly damaging	Het
Ces2g	T	C	8: 105,693,569 (GRCm39)	F417L	probably benign	Het
Clec2g	A	G	6: 128,925,660 (GRCm39)	N23S	unknown	Het
Cntnap2	T	C	6: 46,507,567 (GRCm39)	Y61C	probably damaging	Het
Cog3	T	A	14: 75,979,784 (GRCm39)	E182D	probably benign	Het
Dbpht2	A	G	12: 74,342,624 (GRCm39)		noncoding transcript	Het
Dock4	A	T	12: 40,686,227 (GRCm39)	N154I	probably damaging	Het
Dysf	T	G	6: 84,128,906 (GRCm39)	V1422G	possibly damaging	Het
E2f3	T	C	13: 30,104,159 (GRCm39)	D140G	probably damaging	Het
Efcab3	A	G	11: 104,611,514 (GRCm39)	K452R	probably benign	Het
Epb41l2	T	A	10: 25,317,466 (GRCm39)		probably null	Het
Epha2	A	G	4: 141,035,857 (GRCm39)	K98E	possibly damaging	Het
Esyt1	T	C	10: 128,355,487 (GRCm39)	D444G	probably benign	Het
Fam163a	T	C	1: 155,955,787 (GRCm39)	T2A	probably damaging	Het
Foxp2	A	T	6: 15,379,767 (GRCm39)		probably benign	Het
Gcm2	T	C	13: 41,259,367 (GRCm39)	H34R	probably benign	Het
Gipr	A	G	7: 18,897,996 (GRCm39)	S79P	probably benign	Het
Gli3	T	C	13: 15,823,276 (GRCm39)	S333P	probably damaging	Het
Gm10717	T	G	9: 3,026,317 (GRCm39)	F205C	probably damaging	Het
Gzmk	A	G	13: 113,309,427 (GRCm39)	S208P	probably damaging	Het
Itpkc	T	C	7: 26,907,805 (GRCm39)	D633G	probably damaging	Het
Lama1	G	A	17: 68,098,218 (GRCm39)	R1805H	probably benign	Het
Lama4	T	A	10: 38,909,121 (GRCm39)		probably benign	Het
Lama4	T	C	10: 38,936,182 (GRCm39)	V619A	probably damaging	Het
Notch3	T	C	17: 32,362,402 (GRCm39)	T1408A	probably benign	Het
Nwd2	A	G	5: 63,962,753 (GRCm39)	D779G	probably benign	Het
Nxpe4	A	G	9: 48,304,678 (GRCm39)	Y255C	possibly damaging	Het
Obox6	A	T	7: 15,568,770 (GRCm39)	H35Q	possibly damaging	Het
Or2ab1	A	G	11: 58,489,133 (GRCm39)	I304V	probably damaging	Het
Or8b41	T	A	9: 38,055,025 (GRCm39)	I198N	possibly damaging	Het
Pkig	T	A	2: 163,563,147 (GRCm39)	I26N	possibly damaging	Het
Plekhm2	C	T	4: 141,369,750 (GRCm39)	V82M	possibly damaging	Het
Plppr2	G	A	9: 21,859,220 (GRCm39)	A446T	probably damaging	Het
Psme4	T	A	11: 30,754,353 (GRCm39)	F203L	probably benign	Het
Sh3bp1	A	G	15: 78,787,880 (GRCm39)	K137E	probably damaging	Het
Shisa5	T	A	9: 108,885,108 (GRCm39)	I126N	probably damaging	Het
Slc11a1	T	C	1: 74,414,931 (GRCm39)	L21P	probably benign	Het
Slc35f1	C	T	10: 52,809,291 (GRCm39)	P93S	probably damaging	Het
Slc4a4	A	G	5: 89,194,167 (GRCm39)	T172A	probably damaging	Het
Slc9c1	A	T	16: 45,393,710 (GRCm39)	Y551F	probably benign	Het
Spata31	T	C	13: 65,069,612 (GRCm39)	S587P	probably benign	Het
Syna	C	A	5: 134,588,006 (GRCm39)	M314I	probably benign	Het
Taf5l	A	G	8: 124,730,152 (GRCm39)	L144P	probably damaging	Het
Tbccd1	T	C	16: 22,641,271 (GRCm39)	T369A	probably benign	Het
Tnfrsf11b	A	T	15: 54,119,493 (GRCm39)	C160*	probably null	Het
Trim45	A	G	3: 100,830,283 (GRCm39)	N19S	probably benign	Het
Uba2	A	G	7: 33,850,455 (GRCm39)	F364S	probably damaging	Het
Unc50	T	A	1: 37,476,323 (GRCm39)	L161Q	probably damaging	Het
Uso1	A	T	5: 92,348,992 (GRCm39)		probably null	Het
Usp25	A	G	16: 76,911,838 (GRCm39)	I956V	probably benign	Het
Utf1	C	A	7: 139,524,213 (GRCm39)	L143I	probably damaging	Het
Vmn1r158	C	T	7: 22,490,143 (GRCm39)	C22Y	probably damaging	Het
Vmn1r36	T	A	6: 66,693,756 (GRCm39)	M40L	probably benign	Het
Vmn2r43	A	G	7: 8,258,055 (GRCm39)	V386A	possibly damaging	Het
Vps9d1	C	A	8: 123,973,778 (GRCm39)	R335L	probably damaging	Het
Wasf1	T	A	10: 40,802,585 (GRCm39)	V80D	probably damaging	Het
Wdr72	G	A	9: 74,183,298 (GRCm39)	V1077I	possibly damaging	Het
Wnt8a	A	G	18: 34,675,422 (GRCm39)	M1V	probably null	Het
Zbtb26	A	G	2: 37,326,347 (GRCm39)	S230P	possibly damaging	Het
Zfp335	A	G	2: 164,734,525 (GRCm39)	V1247A	probably damaging	Het
Zfp429	T	C	13: 67,538,505 (GRCm39)	N313S	possibly damaging	Het
Zfp74	A	T	7: 29,634,569 (GRCm39)	C380S	probably damaging	Het
Zfyve21	G	A	12: 111,791,328 (GRCm39)	E134K	probably damaging	Het
Zmynd11	T	C	13: 9,739,616 (GRCm39)	T474A	possibly 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
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
R5454:Htra2	UTSW	6	83,030,995 (GRCm39)	missense	probably damaging	0.96
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'- AGATCAGGGCAAGAGCTTCAC -3'
(R):5'- TTGAACTACAGCTCCGTGAG -3'

Sequencing Primer
(F):5'- AGGGCAAGAGCTTCACACTCTTG -3'
(R):5'- GGTGGATGTATCCTTGAACTT -3'

Posted On

2014-06-23