Incidental Mutation 'R0302:Ankra2'
ID |
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)
|
Stock # |
R0302 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
13 |
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 BKCa+ 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 |
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 |