Mutagenetix > Incidental Mutation

Incidental Mutation 'R1985:Atp2a2'

220435

Institutional Source

Beutler Lab

Gene Symbol

Atp2a2

Ensembl Gene

ENSMUSG00000029467

Gene Name

ATPase, Ca++ transporting, cardiac muscle, slow twitch 2

Synonyms

9530097L16Rik, SERCA2, D5Wsu150e, SERCA2B, sarco/endoplasmic reticulum Ca2+-ATPase 2

MMRRC Submission

039997-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1985 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

122453513-122502225 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 122466836 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 427 (Y427N)

Ref Sequence

ENSEMBL: ENSMUSP00000135935 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000031423] [ENSMUST00000177974] [ENSMUST00000179939]

AlphaFold

O55143

Predicted Effect

probably benign
Transcript: ENSMUST00000031423
AA Change: Y427N

PolyPhen 2 Score 0.025 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000031423
Gene: ENSMUSG00000029467
AA Change: Y427N

Domain	Start	End	E-Value	Type
Cation_ATPase_N	3	77	9e-13	SMART
Pfam:E1-E2_ATPase	92	340	2.1e-66	PFAM
Pfam:Hydrolase	345	714	1.2e-18	PFAM
Pfam:HAD	348	711	1e-18	PFAM
Pfam:Cation_ATPase	418	527	2.5e-24	PFAM
Pfam:Hydrolase_3	682	746	1.9e-7	PFAM
Pfam:Cation_ATPase_C	783	986	2.4e-48	PFAM
transmembrane domain	1015	1032	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177974
AA Change: Y427N

PolyPhen 2 Score 0.025 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000136104
Gene: ENSMUSG00000029467
AA Change: Y427N

Domain	Start	End	E-Value	Type
Cation_ATPase_N	3	77	9e-13	SMART
Pfam:E1-E2_ATPase	92	340	5.1e-66	PFAM
Pfam:Hydrolase	345	714	2.7e-18	PFAM
Pfam:HAD	348	711	2.6e-18	PFAM
Pfam:Cation_ATPase	418	527	4.7e-24	PFAM
Pfam:Hydrolase_3	682	746	7.2e-7	PFAM
Pfam:Cation_ATPase_C	783	986	5.9e-48	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000179939
AA Change: Y427N

PolyPhen 2 Score 0.025 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000135935
Gene: ENSMUSG00000029467
AA Change: Y427N

Domain	Start	End	E-Value	Type
Cation_ATPase_N	3	77	9e-13	SMART
Pfam:E1-E2_ATPase	93	341	9e-69	PFAM
Pfam:HAD	348	711	1.2e-16	PFAM
Pfam:Hydrolase_like2	418	527	3.1e-24	PFAM
Pfam:Hydrolase	496	714	8.7e-24	PFAM
Pfam:Hydrolase_3	682	746	3.4e-7	PFAM
Pfam:Cation_ATPase_C	783	986	1.6e-47	PFAM

Meta Mutation Damage Score

0.4086

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.8%
20x: 94.2%

Validation Efficiency

94% (76/81)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2008]
PHENOTYPE: Targeted homozygous mutants are embryonic lethal while heterozygotes show reduced blood pressure and mildly impaired cardiac contractility and relaxation. Aged heterozygotes for one targeted mutation develop squamous cell tumors of the forestomach, esophagus, oral mucosa, tongue, and skin. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1190007I07Rik	T	A	10: 82,620,217	T37S	possibly damaging	Het
AA792892	A	T	5: 94,384,072	I272L	probably benign	Het
Abhd8	C	A	8: 71,463,513		probably benign	Het
Adam5	A	T	8: 24,746,739	D648E	probably benign	Het
Akr1d1	A	G	6: 37,558,401	D240G	probably damaging	Het
Ankmy2	A	G	12: 36,157,364	H3R	possibly damaging	Het
Anpep	A	C	7: 79,840,857		probably null	Het
Apobr	A	G	7: 126,587,731	T20A	possibly damaging	Het
Camkk2	A	C	5: 122,764,127	S40A	possibly damaging	Het
Camp	T	C	9: 109,848,429	N112S	probably benign	Het
Cbx7	A	G	15: 79,918,390	S229P	probably damaging	Het
Cnot2	T	C	10: 116,527,876	N41S	probably damaging	Het
Dchs1	A	G	7: 105,772,398	F272L	possibly damaging	Het
Dct	T	C	14: 118,036,542	K318E	probably benign	Het
Dhrs11	A	C	11: 84,828,807	L31V	probably damaging	Het
Dnah7a	T	C	1: 53,503,934	D2359G	probably benign	Het
Dnajc7	A	G	11: 100,590,892	S305P	probably benign	Het
Dscc1	CTGAATGAAT	CTGAAT	15: 55,080,176		probably benign	Het
Fam71b	T	C	11: 46,407,866	*666Q	probably null	Het
Flnc	A	G	6: 29,444,416		probably benign	Het
Gm7535	A	G	17: 17,911,538		probably benign	Het
Grtp1	A	G	8: 13,179,376	F313L	probably damaging	Het
Haus6	T	C	4: 86,593,609	Y425C	possibly damaging	Het
Hdac1	T	A	4: 129,528,960	N83Y	possibly damaging	Het
Hdlbp	A	G	1: 93,431,118	I237T	probably damaging	Het
Hfm1	A	T	5: 106,898,576	D481E	probably damaging	Het
Hipk3	T	C	2: 104,434,435	I737V	probably benign	Het
Il23r	T	A	6: 67,490,668		probably null	Het
Il24	G	A	1: 130,882,531	T196I	probably benign	Het
Ints3	C	T	3: 90,400,303		probably null	Het
Kcna6	T	C	6: 126,738,510	E472G	probably benign	Het
Kcnj16	C	T	11: 111,025,583	T357M	probably benign	Het
Kdm4b	T	A	17: 56,401,302	V957E	probably damaging	Het
Kif21b	G	A	1: 136,147,546	D166N	probably damaging	Het
Klhl11	G	T	11: 100,463,244	Q584K	probably benign	Het
Krt9	A	T	11: 100,189,991	M345K	probably benign	Het
Lgr5	T	C	10: 115,495,245		probably benign	Het
Lilr4b	A	T	10: 51,481,735	Q80L	possibly damaging	Het
Lrrc69	T	C	4: 14,708,669	E225G	possibly damaging	Het
Ly9	A	G	1: 171,599,773	S405P	probably damaging	Het
Myh2	A	G	11: 67,180,914	D519G	possibly damaging	Het
Nav3	G	A	10: 109,770,184		probably benign	Het
Nfkb1	G	A	3: 135,615,349	T215I	possibly damaging	Het
Ninj2	A	T	6: 120,198,639		probably benign	Het
Obsl1	A	G	1: 75,505,600	C209R	probably damaging	Het
Olfr1393	T	C	11: 49,280,283	I45T	probably damaging	Het
Olfr314	A	C	11: 58,786,384	D50A	probably damaging	Het
Olfr531	A	T	7: 140,400,800	M82K	possibly damaging	Het
Olfr539	G	A	7: 140,667,821	C171Y	probably damaging	Het
Olfr619	A	T	7: 103,603,672	Y6F	probably benign	Het
Olfr710	A	G	7: 106,944,926	I25T	probably benign	Het
Otud4	G	C	8: 79,640,012	R36P	probably damaging	Het
Pcnt	C	T	10: 76,380,337	R2239H	possibly damaging	Het
Pgbd5	T	A	8: 124,370,592	M491L	probably benign	Het
Pitrm1	A	T	13: 6,558,184	D316V	probably damaging	Het
Plod3	A	G	5: 136,990,853		probably null	Het
Plppr3	A	T	10: 79,867,460	Y63*	probably null	Het
Prickle2	T	C	6: 92,411,452	D323G	probably damaging	Het
Psmd11	A	T	11: 80,445,263	I114F	probably damaging	Het
Ptch1	T	G	13: 63,524,959	E944A	probably benign	Het
Rbp3	C	T	14: 33,956,018	T641M	probably damaging	Het
Rbp3	T	G	14: 33,956,461	S789A	probably benign	Het
Rfxap	C	A	3: 54,807,326	R117L	probably damaging	Het
Rims2	T	A	15: 39,345,314	M171K	probably damaging	Het
Scin	A	G	12: 40,133,908		probably null	Het
Scn11a	A	G	9: 119,754,678	S1624P	probably benign	Het
Slc41a3	G	A	6: 90,642,228	V330M	probably damaging	Het
Slc9c1	A	G	16: 45,550,106	I237V	probably benign	Het
Spag6	A	G	2: 18,732,119	I218V	probably benign	Het
Stam2	T	C	2: 52,709,626	T257A	possibly damaging	Het
Tbc1d24	G	A	17: 24,207,964	R318*	probably null	Het
Tedc2	T	A	17: 24,216,317	E366V	probably damaging	Het
Tedc2	C	A	17: 24,216,318	E366*	probably null	Het
Trpm3	T	A	19: 22,926,082	Y1069N	possibly damaging	Het
Tuba8	A	G	6: 121,220,520	D47G	probably benign	Het
Tulp3	A	T	6: 128,326,806	S277T	probably benign	Het
Wdr7	GTT	GT	18: 63,760,583		probably null	Het
Ybx2	A	G	11: 69,936,468		probably null	Het
Zfp407	C	T	18: 84,559,773	A1072T	probably benign	Het
Zfp788	T	A	7: 41,650,481	I795N	probably damaging	Het

Other mutations in Atp2a2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00576:Atp2a2	APN	5	122458083	splice site	probably null
IGL01459:Atp2a2	APN	5	122469652	missense	probably benign	0.03
IGL01721:Atp2a2	APN	5	122500792	missense	possibly damaging	0.89
IGL02614:Atp2a2	APN	5	122489303	missense	probably benign	0.00
IGL02616:Atp2a2	APN	5	122461684	missense	probably benign	0.07
IGL02826:Atp2a2	APN	5	122489291	missense	probably benign	0.03
IGL02876:Atp2a2	APN	5	122466008	missense	probably benign	0.18
PIT4458001:Atp2a2	UTSW	5	122457309	nonsense	probably null
R0087:Atp2a2	UTSW	5	122460961	missense	probably benign	0.02
R0139:Atp2a2	UTSW	5	122491715	missense	probably damaging	1.00
R0166:Atp2a2	UTSW	5	122466838	missense	possibly damaging	0.69
R0457:Atp2a2	UTSW	5	122469714	missense	probably benign
R0658:Atp2a2	UTSW	5	122457633	splice site	probably benign
R0815:Atp2a2	UTSW	5	122471236	missense	probably benign	0.02
R1282:Atp2a2	UTSW	5	122491754	missense	probably benign	0.00
R1538:Atp2a2	UTSW	5	122457377	missense	probably damaging	1.00
R2111:Atp2a2	UTSW	5	122459546	missense	probably damaging	1.00
R2517:Atp2a2	UTSW	5	122457513	missense	probably damaging	0.99
R4225:Atp2a2	UTSW	5	122469726	missense	probably benign
R4473:Atp2a2	UTSW	5	122457264	missense	probably benign	0.01
R4956:Atp2a2	UTSW	5	122461580	missense	probably benign	0.02
R4969:Atp2a2	UTSW	5	122458491	missense	possibly damaging	0.95
R5242:Atp2a2	UTSW	5	122461946	missense	probably damaging	1.00
R5307:Atp2a2	UTSW	5	122461747	missense	probably benign	0.06
R5497:Atp2a2	UTSW	5	122458169	missense	probably damaging	1.00
R5536:Atp2a2	UTSW	5	122457182	missense	probably benign	0.05
R5629:Atp2a2	UTSW	5	122460096	missense	probably damaging	1.00
R5641:Atp2a2	UTSW	5	122457576	missense	probably damaging	1.00
R6365:Atp2a2	UTSW	5	122461916	missense	probably benign	0.20
R6383:Atp2a2	UTSW	5	122501649	missense	probably benign	0.37
R6534:Atp2a2	UTSW	5	122457198	missense	possibly damaging	0.73
R7162:Atp2a2	UTSW	5	122489324	missense	probably benign	0.00
R7259:Atp2a2	UTSW	5	122466069	missense	probably benign	0.27
R7268:Atp2a2	UTSW	5	122467729	missense	probably benign	0.00
R7465:Atp2a2	UTSW	5	122461700	missense	probably benign
R7489:Atp2a2	UTSW	5	122467767	missense	probably benign
R7567:Atp2a2	UTSW	5	122491784	missense	probably benign	0.29
R7729:Atp2a2	UTSW	5	122491766	missense	probably benign	0.30
R7734:Atp2a2	UTSW	5	122458527	missense	possibly damaging	0.95
R7739:Atp2a2	UTSW	5	122469705	missense	probably damaging	0.98
R7743:Atp2a2	UTSW	5	122461571	missense	probably benign	0.32
R7934:Atp2a2	UTSW	5	122461576	missense	probably benign	0.00
R8822:Atp2a2	UTSW	5	122491709	missense	possibly damaging	0.71
R9123:Atp2a2	UTSW	5	122466855	nonsense	probably null
R9132:Atp2a2	UTSW	5	122461570	missense	probably damaging	1.00
R9170:Atp2a2	UTSW	5	122466024	missense	possibly damaging	0.95
R9254:Atp2a2	UTSW	5	122473252	missense	probably benign	0.23
R9379:Atp2a2	UTSW	5	122473252	missense	probably benign	0.23
R9694:Atp2a2	UTSW	5	122459645	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GGTGCATCAGTGGTCAGAAC -3'
(R):5'- TCAGGGCCATGCTGGAATAG -3'

Sequencing Primer
(F):5'- TGCATCAGTGGTCAGAACATCATG -3'
(R):5'- AGGAGGACCTTCCACAATTTGTC -3'

Posted On

2014-08-25