Incidental Mutation 'R5150:C9orf72'
| ID |
395293 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
C9orf72
|
| Ensembl Gene |
ENSMUSG00000028300 |
| Gene Name |
C9orf72, member of C9orf72-SMCR8 complex |
| Synonyms |
Dennd9, 3110043O21Rik |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R5150 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
4 |
| Chromosomal Location |
35191285-35226153 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 35193270 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Proline
at position 228
(S228P)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000103761
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000084724]
[ENSMUST00000108126]
[ENSMUST00000108127]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000084724
AA Change: S392P
PolyPhen 2
Score 0.891 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000081775
Gene: ENSMUSG00000028300
AA Change: S392P
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:C9orf72-like
|
60 |
325 |
6.8e-90 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000108126
AA Change: S228P
PolyPhen 2
Score 0.918 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000103761
Gene: ENSMUSG00000028300
AA Change: S228P
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:C9orf72-like
|
1 |
161 |
2e-56 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000108127
AA Change: S392P
PolyPhen 2
Score 0.891 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000103762
Gene: ENSMUSG00000028300
AA Change: S392P
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:C9orf72-like
|
61 |
324 |
1.9e-99 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000142628
|
| Meta Mutation Damage Score |
0.1529 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.8%
- 20x: 93.9%
|
| Validation Efficiency |
93% (57/61) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]
PHENOTYPE: Nullizygous mice show splenomegaly and lymphadenopathy. Homozygotes for one allele show reduced body weight, hematocrit and hemoglobin content, lymphopenia, neutrophilia, social interaction deficits and premature death. Homozygotes for another allele show altered macrophage and microglia physiology. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 51 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam33 |
T |
C |
2: 130,895,117 (GRCm39) |
|
probably benign |
Het |
| Ahnak |
T |
C |
19: 8,988,268 (GRCm39) |
V3184A |
possibly damaging |
Het |
| Aoc1 |
A |
G |
6: 48,883,084 (GRCm39) |
N320S |
possibly damaging |
Het |
| Bin2 |
T |
C |
15: 100,543,244 (GRCm39) |
E313G |
probably damaging |
Het |
| Brd10 |
C |
A |
19: 29,782,950 (GRCm39) |
A109S |
probably damaging |
Het |
| Ccdc47 |
T |
C |
11: 106,096,265 (GRCm39) |
D253G |
possibly damaging |
Het |
| Ccdc73 |
A |
G |
2: 104,822,384 (GRCm39) |
T778A |
probably benign |
Het |
| Cops3 |
C |
A |
11: 59,710,839 (GRCm39) |
D377Y |
probably damaging |
Het |
| Cyp4a14 |
A |
C |
4: 115,350,806 (GRCm39) |
V156G |
probably damaging |
Het |
| D6Ertd527e |
C |
G |
6: 87,088,506 (GRCm39) |
T223S |
unknown |
Het |
| Disp1 |
C |
A |
1: 182,871,063 (GRCm39) |
M452I |
probably damaging |
Het |
| Fam210b |
T |
C |
2: 172,193,468 (GRCm39) |
Y94H |
probably damaging |
Het |
| Fbxo45 |
C |
A |
16: 32,065,524 (GRCm39) |
|
probably benign |
Het |
| Flrt2 |
T |
A |
12: 95,745,977 (GRCm39) |
M105K |
possibly damaging |
Het |
| Gm26558 |
G |
A |
2: 70,491,656 (GRCm39) |
|
probably benign |
Het |
| Gpr83 |
T |
G |
9: 14,772,101 (GRCm39) |
L91R |
probably damaging |
Het |
| Greb1l |
TTTAATAACTT |
TTT |
18: 10,555,950 (GRCm39) |
|
probably null |
Het |
| Hmces |
T |
A |
6: 87,910,217 (GRCm39) |
|
probably null |
Het |
| Itgb4 |
C |
T |
11: 115,874,983 (GRCm39) |
R447W |
probably benign |
Het |
| Ksr2 |
A |
C |
5: 117,693,074 (GRCm39) |
E174A |
probably damaging |
Het |
| Lats1 |
A |
G |
10: 7,588,415 (GRCm39) |
T1011A |
probably benign |
Het |
| Lrrc46 |
T |
C |
11: 96,926,957 (GRCm39) |
D120G |
probably damaging |
Het |
| Ncstn |
C |
A |
1: 171,895,151 (GRCm39) |
|
probably benign |
Het |
| Neb |
T |
C |
2: 52,059,130 (GRCm39) |
T6118A |
probably benign |
Het |
| Nipsnap2 |
A |
C |
5: 129,834,175 (GRCm39) |
M272L |
probably benign |
Het |
| Nlgn2 |
C |
T |
11: 69,716,216 (GRCm39) |
R775H |
probably damaging |
Het |
| Or13c7c |
A |
G |
4: 43,836,301 (GRCm39) |
L63P |
probably damaging |
Het |
| Or2n1c |
A |
C |
17: 38,519,208 (GRCm39) |
E24A |
possibly damaging |
Het |
| Or4f15 |
T |
A |
2: 111,814,366 (GRCm39) |
T18S |
probably benign |
Het |
| Or4f61 |
T |
A |
2: 111,922,880 (GRCm39) |
L55F |
possibly damaging |
Het |
| Or4g17 |
T |
A |
2: 111,209,598 (GRCm39) |
D84E |
probably damaging |
Het |
| Or5b118 |
A |
T |
19: 13,448,794 (GRCm39) |
Q153H |
probably benign |
Het |
| Pold1 |
A |
G |
7: 44,185,256 (GRCm39) |
V750A |
possibly damaging |
Het |
| Prdm11 |
C |
T |
2: 92,805,817 (GRCm39) |
E378K |
probably damaging |
Het |
| Ptpn9 |
A |
G |
9: 56,943,954 (GRCm39) |
D276G |
probably benign |
Het |
| Rlf |
A |
T |
4: 121,005,369 (GRCm39) |
F1204I |
probably damaging |
Het |
| Robo1 |
C |
A |
16: 72,769,192 (GRCm39) |
T537K |
possibly damaging |
Het |
| Sec31b |
T |
A |
19: 44,508,970 (GRCm39) |
M670L |
probably benign |
Het |
| Sephs1 |
T |
A |
2: 4,904,321 (GRCm39) |
V233E |
possibly damaging |
Het |
| Serpinb2 |
T |
C |
1: 107,450,939 (GRCm39) |
|
probably null |
Het |
| Sf3b3 |
T |
C |
8: 111,550,008 (GRCm39) |
Q670R |
possibly damaging |
Het |
| Slc8a2 |
A |
C |
7: 15,879,101 (GRCm39) |
D529A |
possibly damaging |
Het |
| Sva |
A |
G |
6: 42,019,093 (GRCm39) |
N88D |
probably benign |
Het |
| Tcf15 |
G |
T |
2: 151,986,051 (GRCm39) |
R169L |
probably damaging |
Het |
| Tfr2 |
A |
G |
5: 137,572,752 (GRCm39) |
T188A |
probably benign |
Het |
| Tshz1 |
T |
A |
18: 84,031,340 (GRCm39) |
K1023* |
probably null |
Het |
| Ttc28 |
A |
G |
5: 111,373,555 (GRCm39) |
N966S |
probably damaging |
Het |
| Unc5c |
T |
A |
3: 141,463,554 (GRCm39) |
I225N |
probably damaging |
Het |
| Ush2a |
T |
C |
1: 188,184,067 (GRCm39) |
L1457S |
possibly damaging |
Het |
| Zbtb34 |
G |
T |
2: 33,301,133 (GRCm39) |
H469Q |
probably damaging |
Het |
| Zfp692 |
T |
C |
11: 58,198,413 (GRCm39) |
M1T |
probably null |
Het |
|
| Other mutations in C9orf72 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00473:C9orf72
|
APN |
4 |
35,213,616 (GRCm39) |
missense |
possibly damaging |
0.57 |
|
IGL00718:C9orf72
|
APN |
4 |
35,213,015 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01284:C9orf72
|
APN |
4 |
35,218,808 (GRCm39) |
missense |
probably damaging |
0.96 |
|
IGL01998:C9orf72
|
APN |
4 |
35,194,179 (GRCm39) |
missense |
probably benign |
0.30 |
|
IGL02185:C9orf72
|
APN |
4 |
35,197,046 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02403:C9orf72
|
APN |
4 |
35,205,887 (GRCm39) |
splice site |
probably benign |
|
|
IGL02823:C9orf72
|
APN |
4 |
35,213,031 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0194:C9orf72
|
UTSW |
4 |
35,197,207 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0471:C9orf72
|
UTSW |
4 |
35,193,257 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1172:C9orf72
|
UTSW |
4 |
35,218,630 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1175:C9orf72
|
UTSW |
4 |
35,218,630 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1765:C9orf72
|
UTSW |
4 |
35,197,098 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4326:C9orf72
|
UTSW |
4 |
35,225,985 (GRCm39) |
unclassified |
probably benign |
|
|
R4327:C9orf72
|
UTSW |
4 |
35,225,985 (GRCm39) |
unclassified |
probably benign |
|
|
R4328:C9orf72
|
UTSW |
4 |
35,225,985 (GRCm39) |
unclassified |
probably benign |
|
|
R4679:C9orf72
|
UTSW |
4 |
35,226,033 (GRCm39) |
unclassified |
probably benign |
|
|
R4844:C9orf72
|
UTSW |
4 |
35,213,565 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
R5528:C9orf72
|
UTSW |
4 |
35,213,556 (GRCm39) |
missense |
probably benign |
0.18 |
|
R5789:C9orf72
|
UTSW |
4 |
35,226,112 (GRCm39) |
unclassified |
probably benign |
|
|
R7790:C9orf72
|
UTSW |
4 |
35,192,997 (GRCm39) |
missense |
unknown |
|
|
R7805:C9orf72
|
UTSW |
4 |
35,194,170 (GRCm39) |
missense |
|
|
|
R8115:C9orf72
|
UTSW |
4 |
35,218,763 (GRCm39) |
missense |
|
|
|
R9049:C9orf72
|
UTSW |
4 |
35,192,964 (GRCm39) |
missense |
unknown |
|
|
R9327:C9orf72
|
UTSW |
4 |
35,205,883 (GRCm39) |
missense |
|
|
|
R9373:C9orf72
|
UTSW |
4 |
35,196,985 (GRCm39) |
missense |
|
|
|
R9590:C9orf72
|
UTSW |
4 |
35,218,557 (GRCm39) |
missense |
|
|
|
R9591:C9orf72
|
UTSW |
4 |
35,218,557 (GRCm39) |
missense |
|
|
|
| Predicted Primers |
PCR Primer
(F):5'- TTCCGAAGAGACTTAAAGGGC -3'
(R):5'- AGCTGAAAAGTCCCCTCCTC -3'
Sequencing Primer
(F):5'- CGAAGAGACTTAAAGGGCTTTTTCCC -3'
(R):5'- CAAGATCTAAGTGCATTAAACTAGGG -3'
|
| Posted On |
2016-06-21 |
Incidental Mutation