Mutagenetix > Incidental Mutation

Incidental Mutation 'R0094:Sptan1'

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) question?

Stock #

R0094 (G1)

Quality Score

Status

Validated

Chromosome

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)].

Sptan1^{tm1.1Gnic/tm1.1Gnic}; MGI:3714925

either: (involves: 129/Sv) or (involves: 129/Sv * C57BL/6)

Homozygotes are phenotypically normal (4).

Sptan1^{Gt(RRQ171)Byg/ Gt(RRQ171)Byg}; MGI: 4330132

B6.129P2-Sptan1^{Gt(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).

Sptan1^{Gt(RRQ171)Byg/ Gt(RRQ171)Byg}; MGI: 4330132

involves: 129P2/OlaHsd

In this genetic background, homozgyotes exhibit disrupted axon initial segment morphology (16).

References

1. Byers, T. J., and Branton, D. (1985) Visualization of the Protein Associations in the Erythrocyte Membrane Skeleton. Proc Natl Acad Sci U S A. 82, 6153-6157.

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.

3. Mohandas, N., and An, X. (2006) New Insights into Function of Red Cell Membrane Proteins and their Interaction with Spectrin-Based Membrane Skeleton. Transfus Clin Biol. 13, 29-30.

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.

6. Bennett, V., and Baines, A. J. (2001) Spectrin and Ankyrin-Based Pathways: Metazoan Inventions for Integrating Cells into Tissues. Physiol Rev. 81, 1353-1392.

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.

8. Nedrelow, J. H., Cianci, C. D., and Morrow, J. S. (2003) C-Src Binds Alpha II Spectrin's Src Homology 3 (SH3) Domain and Blocks Calpain Susceptibility by Phosphorylating Tyr1176. J Biol Chem. 278, 7735-7741.