Mutagenetix > Incidental Mutation

Incidental Mutation 'R0302:Ankra2'

24865

Institutional Source

Beutler Lab

Gene Symbol

Ankra2

Ensembl Gene

ENSMUSG00000021661

Gene Name

ankyrin repeat family A member 2

Synonyms

MMRRC Submission

038514-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.275) question?

Stock #

R0302 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

98399584-98411262 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 98408200 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 216 (S216R)

Ref Sequence

ENSEMBL: ENSMUSP00000117508 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022164] [ENSMUST00000091356] [ENSMUST00000123924] [ENSMUST00000150352] [ENSMUST00000150916] [ENSMUST00000226100]

AlphaFold

Q99PE2

Predicted Effect

probably damaging
Transcript: ENSMUST00000022164
AA Change: S216R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000022164
Gene: ENSMUSG00000021661
AA Change: S216R

Domain	Start	End	E-Value	Type
ANK	180	209	1.45e-6	SMART
ANK	213	242	1.05e-3	SMART
ANK	246	275	1.76e-5	SMART
Blast:ANK	279	308	1e-7	BLAST

Predicted Effect

probably damaging
Transcript: ENSMUST00000091356
AA Change: S56R

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000088915
Gene: ENSMUSG00000021661
AA Change: S56R

Domain	Start	End	E-Value	Type
ANK	20	49	1.45e-6	SMART
ANK	53	82	1.05e-3	SMART
ANK	86	115	1.76e-5	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000123924
AA Change: S216R

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000122701
Gene: ENSMUSG00000021661
AA Change: S216R

Domain	Start	End	E-Value	Type
ANK	180	209	1.45e-6	SMART
ANK	213	242	1.05e-3	SMART
ANK	246	275	1.76e-5	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000150352
AA Change: S216R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000117508
Gene: ENSMUSG00000021661
AA Change: S216R

Domain	Start	End	E-Value	Type
ANK	180	209	1.45e-6	SMART
ANK	213	242	1.05e-3	SMART
ANK	246	275	1.76e-5	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000150916
AA Change: S56R

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000116590
Gene: ENSMUSG00000021661
AA Change: S56R

Domain	Start	End	E-Value	Type
ANK	20	49	1.45e-6	SMART
ANK	53	82	1.05e-3	SMART
ANK	86	115	1.76e-5	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155629

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000223606

Predicted Effect

probably damaging
Transcript: ENSMUST00000226100
AA Change: S56R

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

Meta Mutation Damage Score

0.4594

Coding Region Coverage

1x: 98.8%
3x: 97.8%
10x: 95.1%
20x: 89.5%

Validation Efficiency

100% (63/63)

Allele List at MGI

All alleles(3) : Targeted(2) Gene trapped(1)

Other mutations in this stock

Total: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adprs	T	C	4: 126,211,185 (GRCm39)	E244G	probably benign	Het
Aldh1l2	G	A	10: 83,356,229 (GRCm39)	P54S	probably damaging	Het
Ankdd1a	G	A	9: 65,416,924 (GRCm39)		probably benign	Het
Asah2	A	T	19: 32,030,356 (GRCm39)	N105K	probably benign	Het
Ass1	A	T	2: 31,404,831 (GRCm39)	N371Y	probably damaging	Het
Cacna1s	A	G	1: 136,028,342 (GRCm39)	Y893C	probably benign	Het
Capza2	G	A	6: 17,648,523 (GRCm39)	R15H	probably benign	Het
Cbfa2t2	T	C	2: 154,376,796 (GRCm39)		probably benign	Het
Ccdc96	A	T	5: 36,643,445 (GRCm39)	T484S	possibly damaging	Het
Cckar	GCTTAGCCTCTTCT	GCT	5: 53,857,641 (GRCm39)		probably null	Het
Ccl4	T	A	11: 83,554,280 (GRCm39)		probably benign	Het
Cpt1b	A	G	15: 89,302,073 (GRCm39)	Y702H	probably benign	Het
Cr1l	G	A	1: 194,800,101 (GRCm39)	T153I	probably damaging	Het
Cyth2	C	A	7: 45,460,009 (GRCm39)	E57*	probably null	Het
Daxx	T	A	17: 34,132,594 (GRCm39)	S575T	probably damaging	Het
Depdc5	T	C	5: 33,061,890 (GRCm39)		probably benign	Het
Dnah12	A	G	14: 26,521,956 (GRCm39)	D1923G	probably damaging	Het
Dnah7b	A	G	1: 46,162,937 (GRCm39)	T428A	probably benign	Het
Dnm2	G	T	9: 21,411,639 (GRCm39)	A619S	probably benign	Het
Enpp2	T	C	15: 54,723,457 (GRCm39)	T639A	probably benign	Het
Epsti1	A	T	14: 78,177,366 (GRCm39)	H182L	probably damaging	Het
Exoc3l	C	T	8: 106,020,175 (GRCm39)	R250Q	probably benign	Het
Ggn	G	T	7: 28,870,665 (GRCm39)		probably null	Het
Il1rap	A	G	16: 26,511,544 (GRCm39)	N196S	probably benign	Het
Ints6	T	C	14: 62,946,961 (GRCm39)	T335A	probably damaging	Het
Itga1	G	A	13: 115,148,854 (GRCm39)		probably benign	Het
Kifc3	G	T	8: 95,830,098 (GRCm39)	Q557K	possibly damaging	Het
Krt23	A	G	11: 99,369,027 (GRCm39)	I422T	probably benign	Het
Lcn2	A	G	2: 32,274,901 (GRCm39)		probably benign	Het
Lonp2	A	G	8: 87,364,619 (GRCm39)	T326A	possibly damaging	Het
Lrpprc	T	C	17: 85,047,506 (GRCm39)	I909V	possibly damaging	Het
Lrrc14	G	T	15: 76,598,552 (GRCm39)	R396L	probably benign	Het
Lypd6	T	G	2: 50,055,679 (GRCm39)		probably benign	Het
Man2b1	A	G	8: 85,819,645 (GRCm39)	N610S	probably damaging	Het
Map2	A	T	1: 66,453,987 (GRCm39)	N959I	probably benign	Het
Mctp2	C	T	7: 71,740,012 (GRCm39)	V793I	possibly damaging	Het
Med25	A	C	7: 44,529,982 (GRCm39)		probably benign	Het
Mfsd6	T	C	1: 52,748,616 (GRCm39)	Y83C	probably damaging	Het
Mtbp	A	T	15: 55,488,820 (GRCm39)	M499L	probably damaging	Het
Mtmr10	A	T	7: 63,947,245 (GRCm39)	K53N	probably damaging	Het
Nfat5	T	C	8: 108,085,333 (GRCm39)	I542T	probably damaging	Het
Nr1h3	A	G	2: 91,022,358 (GRCm39)	M90T	probably damaging	Het
Nsmce4a	A	G	7: 130,147,623 (GRCm39)		probably benign	Het
Oprl1	G	A	2: 181,361,021 (GRCm39)	C318Y	probably benign	Het
Or5d40	T	A	2: 88,015,854 (GRCm39)	I211N	possibly damaging	Het
Pbx3	A	T	2: 34,114,572 (GRCm39)	S46T	probably benign	Het
Pign	A	T	1: 105,516,818 (GRCm39)	F575I	possibly damaging	Het
Ptpn13	G	T	5: 103,713,091 (GRCm39)	S1738I	probably benign	Het
Rnf126	G	T	10: 79,595,057 (GRCm39)	P269Q	probably damaging	Het
Ryr3	G	A	2: 112,477,468 (GRCm39)		probably benign	Het
Slc2a7	C	T	4: 150,233,978 (GRCm39)	A31V	probably damaging	Het
Slc6a12	A	G	6: 121,340,218 (GRCm39)	D487G	probably damaging	Het
Son	G	T	16: 91,453,032 (GRCm39)	G593V	probably damaging	Het
Spata31d1a	T	C	13: 59,850,964 (GRCm39)	N388S	probably benign	Het
Spg11	A	T	2: 121,922,668 (GRCm39)	M927K	possibly damaging	Het
Taf13	A	G	3: 108,479,038 (GRCm39)	M1V	probably null	Het
Trim32	G	A	4: 65,531,491 (GRCm39)	R16Q	probably damaging	Het
Trio	A	G	15: 27,902,603 (GRCm39)	F286S	probably damaging	Het
Trpm2	A	C	10: 77,779,824 (GRCm39)		probably benign	Het
Ttc7b	T	C	12: 100,353,438 (GRCm39)	M390V	possibly damaging	Het
Vmn1r184	A	T	7: 25,966,968 (GRCm39)	Q238L	probably damaging	Het
Zfp236	T	C	18: 82,676,213 (GRCm39)	E368G	probably damaging	Het
Zfr2	G	T	10: 81,087,170 (GRCm39)		probably benign	Het

Other mutations in Ankra2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02168:Ankra2	APN	13	98,409,882 (GRCm39)	splice site	probably benign
IGL02807:Ankra2	APN	13	98,408,250 (GRCm39)	missense	probably damaging	1.00
IGL03030:Ankra2	APN	13	98,409,881 (GRCm39)	splice site	probably benign
R0068:Ankra2	UTSW	13	98,409,891 (GRCm39)	nonsense	probably null
R0068:Ankra2	UTSW	13	98,409,891 (GRCm39)	nonsense	probably null
R0499:Ankra2	UTSW	13	98,402,962 (GRCm39)	missense	probably damaging	1.00
R0729:Ankra2	UTSW	13	98,408,235 (GRCm39)	missense	probably damaging	1.00
R1848:Ankra2	UTSW	13	98,407,632 (GRCm39)	missense	probably damaging	1.00
R2185:Ankra2	UTSW	13	98,402,912 (GRCm39)	missense	probably damaging	0.99
R2230:Ankra2	UTSW	13	98,407,646 (GRCm39)	missense	probably damaging	0.99
R2232:Ankra2	UTSW	13	98,407,646 (GRCm39)	missense	probably damaging	0.99
R3898:Ankra2	UTSW	13	98,410,317 (GRCm39)	missense	probably benign	0.13
R4605:Ankra2	UTSW	13	98,402,742 (GRCm39)	intron	probably benign
R4855:Ankra2	UTSW	13	98,409,919 (GRCm39)	missense	probably damaging	1.00
R5806:Ankra2	UTSW	13	98,405,005 (GRCm39)	critical splice donor site	probably null
R5901:Ankra2	UTSW	13	98,407,644 (GRCm39)	missense	probably damaging	0.99
R6478:Ankra2	UTSW	13	98,404,950 (GRCm39)	missense	probably damaging	1.00
R7469:Ankra2	UTSW	13	98,402,882 (GRCm39)	missense	probably benign	0.01
Z1177:Ankra2	UTSW	13	98,408,785 (GRCm39)	missense	possibly damaging	0.73

Predicted Primers

PCR Primer
(F):5'- GCATCCATTGTGCTTGTGTTACGTC -3'
(R):5'- TCAATCAAATGCTGCTACGGACCTG -3'

Sequencing Primer
(F):5'- TCCTTAGTAACCCTAGAGCGTGG -3'
(R):5'- GTGAGCTGGACCGTCATTC -3'

Protein Function and Prediction

Ankra2 encodes the 313-amino acid ankyrin-repeat protein 2 (ANKRA2) that has four C-terminal ankyrin repeats (1). ANKRA2 has been proposed to facilitate endocytosis of vitamin carriers and lipoproteins in the proximal tubules of the kidney through an interaction with the endocytic receptor, megalin (2). ANKRA2 has also been shown to be a binding partner for the α-subunit of rat large-conductance Ca2+-activated K+ channel (rSlo) at the plasma membrane (3). An association with rSlo indicates that ANKRA2 could alter the excitability of neurons by binding directly to endogenous BK_Ca⁺ channels and altering its gating kinetics (3). Yeast two-hybrid screens have identified ANKRA2 as a binding partner of histone deaceytlase 4 (HDAC4) (4) that acts as a repressor (along with HDAC4 and HDAC5) of the Aryl hydrocarbon receptor transcription factor in xenobiotic signaling pathways (5). Ankra2 generates several transcripts. Northern blot analysis determined that a 2.0-kb Ankra2 transcript is ubiquitously expressed, while a 2.7-kb transcript is expressed in the brain, spleen, lung, liver, and kidney; a 2.5-kb transcript is expressed in the testis (2). Another study in rat tissues determined by RT-PCR that rat transcripts were expressed in all tissues, with higher levels in brain subregions and testis (3). Western blot analysis determined that ANKRA2 is enriched in apical membranes of the proximal tubule (2). Immunohistochemistry determined that cytoplasmic ANKRA2 is localized along the plasma membrane (2).

References

1. Long, A. B., and Boss, J. M. (2005) Evolutionary Conservation and Characterization of the Bare Lymphocyte Syndrome Transcription Factor RFX-B and its Paralogue ANKRA2. Immunogenetics. 56, 788-797.

2. Rader, K., Orlando, R. A., Lou, X., and Farquhar, M. G. (2000) Characterization of ANKRA, a Novel Ankyrin Repeat Protein that Interacts with the Cytoplasmic Domain of Megalin. J Am Soc Nephrol. 11, 2167-2178.

3. Lim, H. H., and Park, C. S. (2005) Identification and Functional Characterization of Ankyrin-Repeat Family Protein ANKRA as a Protein Interacting with BKCa Channel. Mol Biol Cell. 16, 1013-1025.

4. Wang, A. H., Gregoire, S., Zika, E., Xiao, L., Li, C. S., Li, H., Wright, K. L., Ting, J. P., and Yang, X. J. (2005) Identification of the Ankyrin Repeat Proteins ANKRA and RFXANK as Novel Partners of Class IIa Histone Deacetylases. J Biol Chem. 280, 29117-29127.

5. Oshima, M., Mimura, J., Yamamoto, M., and Fujii-Kuriyama, Y. (2007) Molecular Mechanism of Transcriptional Repression of AhR Repressor Involving ANKRA2, HDAC4, and HDAC5. Biochem Biophys Res Commun. 364, 276-282.

Posted On

2013-04-16

Science Writer

Anne Murray