Incidental Mutation 'R0094:Sptan1'
ID |
17294 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Sptan1
|
Ensembl Gene |
ENSMUSG00000057738 |
Gene Name |
spectrin alpha, non-erythrocytic 1 |
Synonyms |
alpha-fodrin, alphaII-spectrin, Spna2, 2610027H02Rik, Spna-2 |
MMRRC Submission |
038380-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
R0094 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
2 |
Chromosomal Location |
29855572-29921463 bp(+) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 29896635 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Serine to Proline
at position 1174
(S1174P)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000109348
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000046257]
[ENSMUST00000095083]
[ENSMUST00000100225]
[ENSMUST00000113717]
[ENSMUST00000113719]
[ENSMUST00000129241]
|
AlphaFold |
P16546 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000046257
AA Change: S1174P
PolyPhen 2
Score 0.151 (Sensitivity: 0.92; Specificity: 0.87)
|
SMART Domains |
Protein: ENSMUSP00000047792 Gene: ENSMUSG00000057738 AA Change: S1174P
Domain | Start | End | E-Value | Type |
SPEC
|
47 |
146 |
2.1e-30 |
SMART |
SPEC
|
152 |
252 |
2.6e-35 |
SMART |
SPEC
|
258 |
358 |
4.93e-36 |
SMART |
SPEC
|
364 |
464 |
1.08e-27 |
SMART |
SPEC
|
470 |
570 |
9.01e-30 |
SMART |
SPEC
|
576 |
675 |
3.52e-32 |
SMART |
SPEC
|
681 |
781 |
2.15e-36 |
SMART |
SPEC
|
787 |
887 |
2.45e-40 |
SMART |
SPEC
|
893 |
1068 |
1.18e-24 |
SMART |
SH3
|
970 |
1025 |
8.24e-18 |
SMART |
SPEC
|
1074 |
1210 |
6.52e-27 |
SMART |
SPEC
|
1216 |
1316 |
1.44e-37 |
SMART |
SPEC
|
1322 |
1422 |
4.43e-29 |
SMART |
SPEC
|
1428 |
1528 |
7.54e-32 |
SMART |
SPEC
|
1534 |
1635 |
9.65e-30 |
SMART |
SPEC
|
1641 |
1741 |
2.32e-32 |
SMART |
SPEC
|
1747 |
1847 |
6.98e-36 |
SMART |
SPEC
|
1853 |
1953 |
1.53e-32 |
SMART |
SPEC
|
1959 |
2060 |
6.23e-24 |
SMART |
SPEC
|
2074 |
2174 |
2.08e-11 |
SMART |
SPEC
|
2188 |
2289 |
1.07e-4 |
SMART |
EFh
|
2307 |
2335 |
5.78e-7 |
SMART |
EFh
|
2350 |
2378 |
3.85e-3 |
SMART |
efhand_Ca_insen
|
2382 |
2451 |
6.74e-32 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000095083
AA Change: S1194P
PolyPhen 2
Score 0.188 (Sensitivity: 0.92; Specificity: 0.87)
|
SMART Domains |
Protein: ENSMUSP00000092697 Gene: ENSMUSG00000057738 AA Change: S1194P
Domain | Start | End | E-Value | Type |
SPEC
|
47 |
146 |
2.1e-30 |
SMART |
SPEC
|
152 |
252 |
2.6e-35 |
SMART |
SPEC
|
258 |
358 |
4.93e-36 |
SMART |
SPEC
|
364 |
464 |
1.08e-27 |
SMART |
SPEC
|
470 |
570 |
9.01e-30 |
SMART |
SPEC
|
576 |
675 |
3.52e-32 |
SMART |
SPEC
|
681 |
781 |
2.15e-36 |
SMART |
SPEC
|
787 |
887 |
2.45e-40 |
SMART |
SPEC
|
893 |
1088 |
1.56e-24 |
SMART |
SH3
|
970 |
1025 |
8.24e-18 |
SMART |
SPEC
|
1094 |
1230 |
6.52e-27 |
SMART |
SPEC
|
1236 |
1336 |
1.44e-37 |
SMART |
SPEC
|
1342 |
1442 |
4.43e-29 |
SMART |
SPEC
|
1448 |
1548 |
7.54e-32 |
SMART |
SPEC
|
1554 |
1655 |
9.65e-30 |
SMART |
SPEC
|
1661 |
1761 |
2.32e-32 |
SMART |
SPEC
|
1767 |
1867 |
6.98e-36 |
SMART |
SPEC
|
1873 |
1973 |
1.53e-32 |
SMART |
SPEC
|
1979 |
2080 |
6.23e-24 |
SMART |
SPEC
|
2094 |
2194 |
2.08e-11 |
SMART |
SPEC
|
2208 |
2309 |
1.07e-4 |
SMART |
EFh
|
2327 |
2355 |
5.78e-7 |
SMART |
EFh
|
2370 |
2398 |
3.85e-3 |
SMART |
efhand_Ca_insen
|
2402 |
2471 |
6.74e-32 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000100225
AA Change: S1194P
PolyPhen 2
Score 0.093 (Sensitivity: 0.93; Specificity: 0.85)
|
SMART Domains |
Protein: ENSMUSP00000097797 Gene: ENSMUSG00000057738 AA Change: S1194P
Domain | Start | End | E-Value | Type |
SPEC
|
47 |
146 |
2.1e-30 |
SMART |
SPEC
|
152 |
252 |
2.6e-35 |
SMART |
SPEC
|
258 |
358 |
4.93e-36 |
SMART |
SPEC
|
364 |
464 |
1.08e-27 |
SMART |
SPEC
|
470 |
570 |
9.01e-30 |
SMART |
SPEC
|
576 |
675 |
3.52e-32 |
SMART |
SPEC
|
681 |
781 |
2.15e-36 |
SMART |
SPEC
|
787 |
887 |
2.45e-40 |
SMART |
SPEC
|
893 |
1088 |
1.56e-24 |
SMART |
SH3
|
970 |
1025 |
8.24e-18 |
SMART |
SPEC
|
1094 |
1230 |
6.52e-27 |
SMART |
SPEC
|
1236 |
1336 |
1.44e-37 |
SMART |
SPEC
|
1342 |
1442 |
4.43e-29 |
SMART |
SPEC
|
1448 |
1548 |
7.54e-32 |
SMART |
SPEC
|
1554 |
1660 |
2.06e-24 |
SMART |
SPEC
|
1666 |
1766 |
2.32e-32 |
SMART |
SPEC
|
1772 |
1872 |
6.98e-36 |
SMART |
SPEC
|
1878 |
1978 |
1.53e-32 |
SMART |
SPEC
|
1984 |
2085 |
6.23e-24 |
SMART |
SPEC
|
2099 |
2199 |
2.08e-11 |
SMART |
SPEC
|
2213 |
2314 |
1.07e-4 |
SMART |
EFh
|
2332 |
2360 |
5.78e-7 |
SMART |
EFh
|
2375 |
2403 |
3.85e-3 |
SMART |
efhand_Ca_insen
|
2407 |
2476 |
6.74e-32 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000113717
AA Change: S1174P
PolyPhen 2
Score 0.188 (Sensitivity: 0.92; Specificity: 0.87)
|
SMART Domains |
Protein: ENSMUSP00000109346 Gene: ENSMUSG00000057738 AA Change: S1174P
Domain | Start | End | E-Value | Type |
SPEC
|
47 |
146 |
2.1e-30 |
SMART |
SPEC
|
152 |
252 |
2.6e-35 |
SMART |
SPEC
|
258 |
358 |
4.93e-36 |
SMART |
SPEC
|
364 |
464 |
1.08e-27 |
SMART |
SPEC
|
470 |
570 |
9.01e-30 |
SMART |
SPEC
|
576 |
675 |
3.52e-32 |
SMART |
SPEC
|
681 |
781 |
2.15e-36 |
SMART |
SPEC
|
787 |
887 |
2.45e-40 |
SMART |
SPEC
|
893 |
1068 |
1.18e-24 |
SMART |
SH3
|
970 |
1025 |
8.24e-18 |
SMART |
SPEC
|
1074 |
1210 |
6.52e-27 |
SMART |
SPEC
|
1216 |
1316 |
1.44e-37 |
SMART |
SPEC
|
1322 |
1422 |
4.43e-29 |
SMART |
SPEC
|
1428 |
1528 |
7.54e-32 |
SMART |
SPEC
|
1534 |
1640 |
2.06e-24 |
SMART |
SPEC
|
1646 |
1746 |
2.32e-32 |
SMART |
SPEC
|
1752 |
1852 |
6.98e-36 |
SMART |
SPEC
|
1858 |
1958 |
1.53e-32 |
SMART |
SPEC
|
1964 |
2065 |
6.23e-24 |
SMART |
SPEC
|
2079 |
2179 |
2.08e-11 |
SMART |
SPEC
|
2193 |
2294 |
1.07e-4 |
SMART |
EFh
|
2312 |
2340 |
5.78e-7 |
SMART |
EFh
|
2355 |
2383 |
3.85e-3 |
SMART |
efhand_Ca_insen
|
2387 |
2456 |
6.74e-32 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000113719
AA Change: S1174P
PolyPhen 2
Score 0.373 (Sensitivity: 0.90; Specificity: 0.89)
|
SMART Domains |
Protein: ENSMUSP00000109348 Gene: ENSMUSG00000057738 AA Change: S1174P
Domain | Start | End | E-Value | Type |
SPEC
|
47 |
146 |
2.1e-30 |
SMART |
SPEC
|
152 |
252 |
2.6e-35 |
SMART |
SPEC
|
258 |
358 |
4.93e-36 |
SMART |
SPEC
|
364 |
464 |
1.08e-27 |
SMART |
SPEC
|
470 |
570 |
9.01e-30 |
SMART |
SPEC
|
576 |
675 |
3.52e-32 |
SMART |
SPEC
|
681 |
781 |
2.15e-36 |
SMART |
SPEC
|
787 |
887 |
2.45e-40 |
SMART |
SPEC
|
893 |
1068 |
1.18e-24 |
SMART |
SH3
|
970 |
1025 |
8.24e-18 |
SMART |
SPEC
|
1074 |
1210 |
6.52e-27 |
SMART |
SPEC
|
1216 |
1316 |
1.44e-37 |
SMART |
SPEC
|
1322 |
1422 |
4.43e-29 |
SMART |
SPEC
|
1428 |
1528 |
7.54e-32 |
SMART |
SPEC
|
1534 |
1640 |
2.06e-24 |
SMART |
SPEC
|
1646 |
1746 |
2.32e-32 |
SMART |
SPEC
|
1752 |
1852 |
6.98e-36 |
SMART |
SPEC
|
1858 |
1958 |
1.53e-32 |
SMART |
SPEC
|
1964 |
2065 |
6.23e-24 |
SMART |
SPEC
|
2079 |
2179 |
2.08e-11 |
SMART |
SPEC
|
2193 |
2315 |
3.27e0 |
SMART |
EFh
|
2333 |
2361 |
5.78e-7 |
SMART |
EFh
|
2376 |
2404 |
3.85e-3 |
SMART |
efhand_Ca_insen
|
2408 |
2477 |
6.74e-32 |
SMART |
|
Predicted Effect |
unknown
Transcript: ENSMUST00000129241
AA Change: S1194P
|
SMART Domains |
Protein: ENSMUSP00000121116 Gene: ENSMUSG00000057738 AA Change: S1194P
Domain | Start | End | E-Value | Type |
Pfam:Spectrin
|
1 |
65 |
9.9e-10 |
PFAM |
SPEC
|
78 |
178 |
2.08e-11 |
SMART |
SPEC
|
192 |
314 |
3.27e0 |
SMART |
EFh
|
332 |
360 |
5.78e-7 |
SMART |
EFh
|
375 |
403 |
3.85e-3 |
SMART |
efhand_Ca_insen
|
407 |
476 |
6.74e-32 |
SMART |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000149038
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000202844
|
Meta Mutation Damage Score |
0.0785 |
Coding Region Coverage |
- 1x: 84.5%
- 3x: 75.9%
- 10x: 43.5%
- 20x: 12.9%
|
Validation Efficiency |
86% (51/59) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010] PHENOTYPE: Homozygous deletion of the exons encoding the CCC region are normal. Mice homozygous for a gene trap allele exhibit embryonic lethality and abnormal nervous system, heart and craniofacial morphology. [provided by MGI curators]
|
Allele List at MGI |
All alleles(76) : Targeted(1) Gene trapped(75)
|
Other mutations in this stock |
Total: 39 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
1700006A11Rik |
T |
C |
3: 124,203,427 (GRCm39) |
|
probably benign |
Het |
4930432E11Rik |
A |
G |
7: 29,260,236 (GRCm39) |
|
noncoding transcript |
Het |
4931429L15Rik |
T |
A |
9: 46,218,184 (GRCm39) |
T185S |
possibly damaging |
Het |
Ahnak |
T |
A |
19: 8,991,257 (GRCm39) |
D4180E |
probably benign |
Het |
Amotl1 |
A |
G |
9: 14,486,683 (GRCm39) |
S441P |
probably benign |
Het |
Ankrd12 |
A |
T |
17: 66,277,171 (GRCm39) |
D2034E |
probably damaging |
Het |
B3gnt2 |
T |
C |
11: 22,786,655 (GRCm39) |
R178G |
probably damaging |
Het |
Colgalt1 |
T |
C |
8: 72,075,802 (GRCm39) |
V483A |
probably damaging |
Het |
Ctsj |
A |
C |
13: 61,151,519 (GRCm39) |
|
probably null |
Het |
Dap3 |
T |
A |
3: 88,834,335 (GRCm39) |
M294L |
probably benign |
Het |
Ddias |
T |
C |
7: 92,509,108 (GRCm39) |
N269S |
possibly damaging |
Het |
Dsg2 |
A |
T |
18: 20,724,910 (GRCm39) |
T439S |
probably benign |
Het |
Eif2b1 |
A |
G |
5: 124,709,829 (GRCm39) |
F250L |
probably benign |
Het |
Emc1 |
T |
A |
4: 139,087,796 (GRCm39) |
F100Y |
probably damaging |
Het |
Hfm1 |
T |
A |
5: 107,065,344 (GRCm39) |
M112L |
probably benign |
Het |
Lipg |
T |
C |
18: 75,078,917 (GRCm39) |
Y445C |
probably benign |
Het |
Lrp1b |
T |
C |
2: 41,172,042 (GRCm39) |
|
probably benign |
Het |
Ltbp2 |
A |
G |
12: 84,846,200 (GRCm39) |
Y897H |
probably damaging |
Het |
Mfap5 |
G |
A |
6: 122,502,951 (GRCm39) |
V54I |
probably damaging |
Het |
Mvd |
C |
T |
8: 123,166,442 (GRCm39) |
R65H |
probably benign |
Het |
Mybpc2 |
A |
G |
7: 44,166,328 (GRCm39) |
Y221H |
probably damaging |
Het |
Nbeal1 |
T |
A |
1: 60,344,468 (GRCm39) |
I2323N |
possibly damaging |
Het |
Or14c40 |
A |
G |
7: 86,313,502 (GRCm39) |
S211G |
probably benign |
Het |
Otol1 |
G |
A |
3: 69,926,016 (GRCm39) |
A64T |
probably benign |
Het |
Pcdh8 |
G |
T |
14: 80,005,588 (GRCm39) |
D933E |
probably damaging |
Het |
Pkd1 |
A |
G |
17: 24,800,250 (GRCm39) |
T3004A |
possibly damaging |
Het |
Pkhd1 |
T |
A |
1: 20,279,470 (GRCm39) |
R2949S |
probably damaging |
Het |
Ptpro |
T |
C |
6: 137,363,350 (GRCm39) |
Y495H |
probably benign |
Het |
Rad54b |
T |
C |
4: 11,599,681 (GRCm39) |
V72A |
possibly damaging |
Het |
Ranbp3 |
A |
G |
17: 57,016,338 (GRCm39) |
|
probably benign |
Het |
Rpa2 |
T |
C |
4: 132,497,893 (GRCm39) |
S52P |
probably damaging |
Het |
Serping1 |
T |
G |
2: 84,603,620 (GRCm39) |
R140S |
probably benign |
Het |
Slc34a2 |
T |
C |
5: 53,221,310 (GRCm39) |
F252S |
probably benign |
Het |
Spata45 |
A |
G |
1: 190,772,059 (GRCm39) |
|
probably benign |
Het |
Ss18l2 |
T |
C |
9: 121,541,699 (GRCm39) |
L64P |
probably benign |
Het |
Tmem81 |
A |
G |
1: 132,435,787 (GRCm39) |
I198V |
probably benign |
Het |
Trappc9 |
A |
T |
15: 72,894,929 (GRCm38) |
|
probably benign |
Het |
Ubr3 |
C |
T |
2: 69,781,706 (GRCm39) |
T628I |
probably damaging |
Het |
Zzef1 |
C |
T |
11: 72,708,791 (GRCm39) |
T130I |
probably benign |
Het |
|
Other mutations in Sptan1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00668:Sptan1
|
APN |
2 |
29,883,968 (GRCm39) |
critical splice donor site |
probably null |
|
IGL00932:Sptan1
|
APN |
2 |
29,905,622 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL00945:Sptan1
|
APN |
2 |
29,890,083 (GRCm39) |
splice site |
probably benign |
|
IGL01070:Sptan1
|
APN |
2 |
29,904,185 (GRCm39) |
critical splice donor site |
probably null |
|
IGL01625:Sptan1
|
APN |
2 |
29,916,126 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01657:Sptan1
|
APN |
2 |
29,908,491 (GRCm39) |
missense |
probably benign |
0.12 |
IGL01795:Sptan1
|
APN |
2 |
29,908,501 (GRCm39) |
missense |
probably benign |
0.07 |
IGL01982:Sptan1
|
APN |
2 |
29,909,980 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02040:Sptan1
|
APN |
2 |
29,903,725 (GRCm39) |
missense |
probably benign |
0.43 |
IGL02158:Sptan1
|
APN |
2 |
29,920,336 (GRCm39) |
missense |
probably damaging |
0.97 |
IGL02370:Sptan1
|
APN |
2 |
29,920,752 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL02507:Sptan1
|
APN |
2 |
29,906,067 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02552:Sptan1
|
APN |
2 |
29,908,486 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL02690:Sptan1
|
APN |
2 |
29,888,195 (GRCm39) |
missense |
possibly damaging |
0.78 |
IGL02715:Sptan1
|
APN |
2 |
29,868,588 (GRCm39) |
missense |
probably benign |
0.03 |
IGL02725:Sptan1
|
APN |
2 |
29,886,055 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL03033:Sptan1
|
APN |
2 |
29,881,045 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03304:Sptan1
|
APN |
2 |
29,876,505 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03405:Sptan1
|
APN |
2 |
29,915,593 (GRCm39) |
missense |
probably damaging |
0.99 |
R0058:Sptan1
|
UTSW |
2 |
29,883,708 (GRCm39) |
splice site |
probably null |
|
R0058:Sptan1
|
UTSW |
2 |
29,883,708 (GRCm39) |
splice site |
probably null |
|
R0066:Sptan1
|
UTSW |
2 |
29,893,679 (GRCm39) |
splice site |
probably benign |
|
R0066:Sptan1
|
UTSW |
2 |
29,893,679 (GRCm39) |
splice site |
probably benign |
|
R0071:Sptan1
|
UTSW |
2 |
29,893,354 (GRCm39) |
nonsense |
probably null |
|
R0071:Sptan1
|
UTSW |
2 |
29,893,354 (GRCm39) |
nonsense |
probably null |
|
R0230:Sptan1
|
UTSW |
2 |
29,900,704 (GRCm39) |
splice site |
probably benign |
|
R0242:Sptan1
|
UTSW |
2 |
29,908,413 (GRCm39) |
missense |
probably benign |
0.00 |
R0242:Sptan1
|
UTSW |
2 |
29,908,413 (GRCm39) |
missense |
probably benign |
0.00 |
R0366:Sptan1
|
UTSW |
2 |
29,882,764 (GRCm39) |
splice site |
probably null |
|
R0368:Sptan1
|
UTSW |
2 |
29,883,927 (GRCm39) |
missense |
probably benign |
0.29 |
R0396:Sptan1
|
UTSW |
2 |
29,881,045 (GRCm39) |
missense |
probably damaging |
1.00 |
R0423:Sptan1
|
UTSW |
2 |
29,918,684 (GRCm39) |
missense |
probably null |
|
R0448:Sptan1
|
UTSW |
2 |
29,916,822 (GRCm39) |
missense |
probably damaging |
1.00 |
R0485:Sptan1
|
UTSW |
2 |
29,903,860 (GRCm39) |
splice site |
probably benign |
|
R0580:Sptan1
|
UTSW |
2 |
29,897,587 (GRCm39) |
missense |
probably damaging |
0.99 |
R0739:Sptan1
|
UTSW |
2 |
29,903,530 (GRCm39) |
missense |
probably damaging |
1.00 |
R0924:Sptan1
|
UTSW |
2 |
29,906,040 (GRCm39) |
missense |
probably damaging |
0.98 |
R0930:Sptan1
|
UTSW |
2 |
29,906,040 (GRCm39) |
missense |
probably damaging |
0.98 |
R0961:Sptan1
|
UTSW |
2 |
29,870,075 (GRCm39) |
splice site |
probably null |
|
R1352:Sptan1
|
UTSW |
2 |
29,911,199 (GRCm39) |
splice site |
probably benign |
|
R1456:Sptan1
|
UTSW |
2 |
29,870,215 (GRCm39) |
critical splice donor site |
probably null |
|
R1537:Sptan1
|
UTSW |
2 |
29,916,034 (GRCm39) |
missense |
possibly damaging |
0.95 |
R1542:Sptan1
|
UTSW |
2 |
29,917,139 (GRCm39) |
missense |
probably damaging |
1.00 |
R1612:Sptan1
|
UTSW |
2 |
29,893,348 (GRCm39) |
missense |
probably damaging |
1.00 |
R1623:Sptan1
|
UTSW |
2 |
29,876,432 (GRCm39) |
missense |
probably damaging |
0.96 |
R1834:Sptan1
|
UTSW |
2 |
29,882,013 (GRCm39) |
splice site |
probably benign |
|
R1879:Sptan1
|
UTSW |
2 |
29,885,540 (GRCm39) |
missense |
probably damaging |
1.00 |
R1893:Sptan1
|
UTSW |
2 |
29,910,472 (GRCm39) |
missense |
probably damaging |
0.98 |
R1914:Sptan1
|
UTSW |
2 |
29,901,048 (GRCm39) |
missense |
probably benign |
0.00 |
R1915:Sptan1
|
UTSW |
2 |
29,901,048 (GRCm39) |
missense |
probably benign |
0.00 |
R2022:Sptan1
|
UTSW |
2 |
29,897,573 (GRCm39) |
missense |
probably damaging |
0.96 |
R2050:Sptan1
|
UTSW |
2 |
29,892,250 (GRCm39) |
missense |
probably benign |
|
R2103:Sptan1
|
UTSW |
2 |
29,920,483 (GRCm39) |
missense |
probably damaging |
1.00 |
R2162:Sptan1
|
UTSW |
2 |
29,908,588 (GRCm39) |
splice site |
probably benign |
|
R2931:Sptan1
|
UTSW |
2 |
29,908,500 (GRCm39) |
missense |
probably benign |
|
R3726:Sptan1
|
UTSW |
2 |
29,908,431 (GRCm39) |
missense |
possibly damaging |
0.59 |
R4170:Sptan1
|
UTSW |
2 |
29,920,037 (GRCm39) |
missense |
possibly damaging |
0.93 |
R4235:Sptan1
|
UTSW |
2 |
29,916,600 (GRCm39) |
missense |
probably damaging |
1.00 |
R4378:Sptan1
|
UTSW |
2 |
29,915,581 (GRCm39) |
missense |
probably damaging |
1.00 |
R4424:Sptan1
|
UTSW |
2 |
29,919,721 (GRCm39) |
intron |
probably benign |
|
R4718:Sptan1
|
UTSW |
2 |
29,921,074 (GRCm39) |
missense |
probably damaging |
1.00 |
R4777:Sptan1
|
UTSW |
2 |
29,886,447 (GRCm39) |
missense |
probably damaging |
0.98 |
R4849:Sptan1
|
UTSW |
2 |
29,901,054 (GRCm39) |
missense |
probably damaging |
1.00 |
R5158:Sptan1
|
UTSW |
2 |
29,868,455 (GRCm39) |
missense |
probably damaging |
1.00 |
R5180:Sptan1
|
UTSW |
2 |
29,883,736 (GRCm39) |
intron |
probably benign |
|
R5181:Sptan1
|
UTSW |
2 |
29,883,736 (GRCm39) |
intron |
probably benign |
|
R5383:Sptan1
|
UTSW |
2 |
29,901,340 (GRCm39) |
missense |
probably damaging |
1.00 |
R5573:Sptan1
|
UTSW |
2 |
29,876,504 (GRCm39) |
nonsense |
probably null |
|
R5592:Sptan1
|
UTSW |
2 |
29,876,731 (GRCm39) |
intron |
probably benign |
|
R5639:Sptan1
|
UTSW |
2 |
29,881,005 (GRCm39) |
nonsense |
probably null |
|
R5801:Sptan1
|
UTSW |
2 |
29,920,613 (GRCm39) |
splice site |
probably null |
|
R5947:Sptan1
|
UTSW |
2 |
29,884,379 (GRCm39) |
critical splice donor site |
probably null |
|
R6056:Sptan1
|
UTSW |
2 |
29,886,794 (GRCm39) |
missense |
probably benign |
0.36 |
R6090:Sptan1
|
UTSW |
2 |
29,883,899 (GRCm39) |
missense |
probably damaging |
1.00 |
R6146:Sptan1
|
UTSW |
2 |
29,894,535 (GRCm39) |
missense |
probably benign |
0.01 |
R6254:Sptan1
|
UTSW |
2 |
29,897,561 (GRCm39) |
missense |
possibly damaging |
0.93 |
R6366:Sptan1
|
UTSW |
2 |
29,910,467 (GRCm39) |
missense |
possibly damaging |
0.47 |
R6378:Sptan1
|
UTSW |
2 |
29,908,527 (GRCm39) |
missense |
probably damaging |
1.00 |
R6521:Sptan1
|
UTSW |
2 |
29,910,467 (GRCm39) |
missense |
possibly damaging |
0.47 |
R6877:Sptan1
|
UTSW |
2 |
29,920,985 (GRCm39) |
missense |
probably damaging |
0.99 |
R7173:Sptan1
|
UTSW |
2 |
29,873,221 (GRCm39) |
missense |
probably benign |
0.02 |
R7248:Sptan1
|
UTSW |
2 |
29,892,311 (GRCm39) |
missense |
probably benign |
0.10 |
R7282:Sptan1
|
UTSW |
2 |
29,876,941 (GRCm39) |
missense |
probably damaging |
1.00 |
R7527:Sptan1
|
UTSW |
2 |
29,870,209 (GRCm39) |
missense |
probably damaging |
1.00 |
R7585:Sptan1
|
UTSW |
2 |
29,890,068 (GRCm39) |
missense |
probably benign |
0.06 |
R7779:Sptan1
|
UTSW |
2 |
29,911,319 (GRCm39) |
missense |
probably damaging |
1.00 |
R8051:Sptan1
|
UTSW |
2 |
29,920,171 (GRCm39) |
missense |
probably damaging |
1.00 |
R8055:Sptan1
|
UTSW |
2 |
29,884,351 (GRCm39) |
missense |
probably benign |
0.22 |
R8103:Sptan1
|
UTSW |
2 |
29,910,055 (GRCm39) |
missense |
probably damaging |
1.00 |
R8283:Sptan1
|
UTSW |
2 |
29,870,212 (GRCm39) |
missense |
probably damaging |
1.00 |
R8507:Sptan1
|
UTSW |
2 |
29,916,596 (GRCm39) |
missense |
probably damaging |
1.00 |
R8963:Sptan1
|
UTSW |
2 |
29,873,744 (GRCm39) |
missense |
possibly damaging |
0.92 |
R9126:Sptan1
|
UTSW |
2 |
29,920,597 (GRCm39) |
missense |
probably damaging |
0.99 |
R9206:Sptan1
|
UTSW |
2 |
29,920,724 (GRCm39) |
missense |
possibly damaging |
0.90 |
R9273:Sptan1
|
UTSW |
2 |
29,880,977 (GRCm39) |
missense |
possibly damaging |
0.88 |
X0028:Sptan1
|
UTSW |
2 |
29,910,042 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Protein Function and Prediction |
Sptan1 encodes αII-spectrin (also named α-fodrin), a component of the cytoskeletal spectrin scaffold located under the lipid bilayer. Spectrins are long, flexible proteins composed of two subunits, α and β, that intertwine to form α/β heterodimers. Within the membrane skeleton, the α/β heterodimers self-associate to form (α/β)2 tetramers (1;2). The nodes of (α/β)2 tetramers are subsequently cross-linked by actin filaments (3). The spectrin subunits are composed of a succession of triple helical repeats. αII-spectrin is ubiquitously expressed and is the major α-spectrin expressed in nonerythroid cells (4). αII-spectrin is unique to erythroid αI-spectrin in that it has a region of 36 amino acids in the middle part of the protein near an SH3 domain that has protease cleavage sites and a binding site for calmodulin (5). The αII/β heterodimer has been shown to have several functions including, but not limited to: formation of specialized plasma membrane domains defining apical-basolateral and planar polarity in epithelial cells, muscle, and neurons (6); a scaffold upon which calcium-mediated and tyrosine kinase-phosphatases signal transduction pathways meet (7;8); a tumor suppressor that regulates TGF-β–SMAD (9); a cargo selection mechanism in the secretory and endocytic pathways (10); a tether that links trafficking vesicles to microtubules (11); and a nuclear scaffold organizer (12). Mutations in SPTAN1 have been linked to early infantile epileptic encephalopathy [OMIM: 613477; (13;14)]. Sptan1tm1.1Gnic/tm1.1Gnic; MGI:3714925
either: (involves: 129/Sv) or (involves: 129/Sv * C57BL/6)
Homozygotes are phenotypically normal (4). Sptan1Gt(RRQ171)Byg/ Gt(RRQ171)Byg; MGI: 4330132
B6.129P2-Sptan1Gt(RRQ171)Byg
Homozygotes exhibit partial embryonic lethality during organogenesis and complete lethality throughout fetal growth and development (between E12.5 and E16.5) (15). Homozygotes display abnormal nervous system, heart and craniofacial morphology (15). Sptan1Gt(RRQ171)Byg/ Gt(RRQ171)Byg; MGI: 4330132
involves: 129P2/OlaHsd
In this genetic background, homozgyotes exhibit disrupted axon initial segment morphology (16).
|
References |
2. Leto, T. L., Fortugno-Erikson, D., Barton, D., Yang-Feng, T. L., Francke, U., Harris, A. S., Morrow, J. S., Marchesi, V. T., and Benz, E. J.,Jr. (1988) Comparison of Nonerythroid Alpha-Spectrin Genes Reveals Strict Homology among Diverse Species. Mol Cell Biol. 8, 1-9.
4. Meary, F., Metral, S., Ferreira, C., Eladari, D., Colin, Y., Lecomte, M. C., and Nicolas, G. (2007) A Mutant alphaII-Spectrin Designed to Resist Calpain and Caspase Cleavage Questions the Functional Importance of this Process in Vivo. J Biol Chem. 282, 14226-14237.
5. Rotter, B., Kroviarski, Y., Nicolas, G., Dhermy, D., and Lecomte, M. C. (2004) AlphaII-Spectrin is an in Vitro Target for Caspase-2, and its Cleavage is Regulated by Calmodulin Binding. Biochem J. 378, 161-168.
7. Nicolas, G., Fournier, C. M., Galand, C., Malbert-Colas, L., Bournier, O., Kroviarski, Y., Bourgeois, M., Camonis, J. H., Dhermy, D., Grandchamp, B., and Lecomte, M. C. (2002) Tyrosine Phosphorylation Regulates Alpha II Spectrin Cleavage by Calpain. Mol Cell Biol. 22, 3527-3536.
9. Tang, Y., Katuri, V., Dillner, A., Mishra, B., Deng, C. X., and Mishra, L. (2003) Disruption of Transforming Growth Factor-Beta Signaling in ELF Beta-Spectrin-Deficient Mice. Science. 299, 574-577.
11. Muresan, V., Stankewich, M. C., Steffen, W., Morrow, J. S., Holzbaur, E. L., and Schnapp, B. J. (2001) Dynactin-Dependent, Dynein-Driven Vesicle Transport in the Absence of Membrane Proteins: A Role for Spectrin and Acidic Phospholipids. Mol Cell. 7, 173-183.
13. Saitsu, H., Tohyama, J., Kumada, T., Egawa, K., Hamada, K., Okada, I., Mizuguchi, T., Osaka, H., Miyata, R., Furukawa, T., Haginoya, K., Hoshino, H., Goto, T., Hachiya, Y., Yamagata, T., Saitoh, S., Nagai, T., Nishiyama, K., Nishimura, A., Miyake, N., Komada, M., Hayashi, K., Hirai, S., Ogata, K., Kato, M., Fukuda, A., and Matsumoto, N. (2010) Dominant-Negative Mutations in Alpha-II Spectrin Cause West Syndrome with Severe Cerebral Hypomyelination, Spastic Quadriplegia, and Developmental Delay. Am J Hum Genet. 86, 881-891.
14. Hamdan, F. F., Saitsu, H., Nishiyama, K., Gauthier, J., Dobrzeniecka, S., Spiegelman, D., Lacaille, J. C., Decarie, J. C., Matsumoto, N., Rouleau, G. A., and Michaud, J. L. (2012) Identification of a Novel in-Frame De Novo Mutation in SPTAN1 in Intellectual Disability and Pontocerebellar Atrophy. Eur J Hum Genet. 20, 796-800.
15. Stankewich, M. C., Cianci, C. D., Stabach, P. R., Ji, L., Nath, A., and Morrow, J. S. (2011) Cell Organization, Growth, and Neural and Cardiac Development Require alphaII-Spectrin. J Cell Sci. 124, 3956-3966.
16. Galiano, M. R., Jha, S., Ho, T. S., Zhang, C., Ogawa, Y., Chang, K. J., Stankewich, M. C., Mohler, P. J., and Rasband, M. N. (2012) A Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly. Cell. 149, 1125-1139.
|
Posted On |
2013-01-20 |
Science Writer |
Anne Murray |