Incidental Mutation 'R5889:Chrna4'
| ID |
456206 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Chrna4
|
| Ensembl Gene |
ENSMUSG00000027577 |
| Gene Name |
cholinergic receptor, nicotinic, alpha polypeptide 4 |
| Synonyms |
a4 nicotinic receptor, Acra-4, alpha4-nAChR, Acra4, alpha4 nAChR |
| MMRRC Submission |
044090-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.178)
|
| Stock # |
R5889 (G1)
|
| Quality Score |
84 |
|
Status
|
Validated
|
| Chromosome |
2 |
| Chromosomal Location |
180664104-180685339 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to C
at 180670451 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Tryptophan
at position 435
(L435W)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000066338
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000067120]
[ENSMUST00000108851]
|
| AlphaFold |
O70174 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000067120
AA Change: L435W
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000066338
Gene: ENSMUSG00000027577
AA Change: L435W
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
30 |
N/A |
INTRINSIC |
|
Pfam:Neur_chan_LBD
|
39 |
245 |
1.4e-76 |
PFAM |
|
Pfam:Neur_chan_memb
|
252 |
620 |
1.9e-107 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000108851
AA Change: L435W
PolyPhen 2
Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000104479
Gene: ENSMUSG00000027577
AA Change: L435W
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
30 |
N/A |
INTRINSIC |
|
Pfam:Neur_chan_LBD
|
39 |
245 |
8.4e-79 |
PFAM |
|
Pfam:Neur_chan_memb
|
252 |
620 |
3.3e-112 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000135766
|
| SMART Domains |
Protein: ENSMUSP00000125724
Gene: ENSMUSG00000027577
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
30 |
N/A |
INTRINSIC |
|
Pfam:Neur_chan_LBD
|
39 |
130 |
9.2e-37 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000198922
|
| Meta Mutation Damage Score |
0.6467 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.6%
- 20x: 92.3%
|
| Validation Efficiency |
100% (63/63) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
PHENOTYPE: Nullizygous mice may show reduced chemically-elicited analgesia, susceptibility to seizures, increased anxiety, and altered behavioral responses to nicotine or a new environment. Homozygotes for any of several knock-in alleles exhibit altered nervous system physiology and/or sensitivity to nicotine. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 57 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930568D16Rik |
T |
C |
2: 35,244,461 (GRCm39) |
E297G |
probably damaging |
Het |
| Astn1 |
C |
T |
1: 158,427,950 (GRCm39) |
P707L |
possibly damaging |
Het |
| Cep290 |
T |
C |
10: 100,334,936 (GRCm39) |
S319P |
possibly damaging |
Het |
| Cilp |
C |
A |
9: 65,187,625 (GRCm39) |
A1240D |
possibly damaging |
Het |
| Col17a1 |
A |
G |
19: 47,637,511 (GRCm39) |
F1249S |
possibly damaging |
Het |
| Creb3l3 |
T |
C |
10: 80,928,367 (GRCm39) |
|
probably benign |
Het |
| Cyp4f40 |
C |
A |
17: 32,894,731 (GRCm39) |
T432N |
probably benign |
Het |
| Dsg1c |
T |
G |
18: 20,416,658 (GRCm39) |
I853R |
possibly damaging |
Het |
| Ebna1bp2 |
T |
A |
4: 118,478,620 (GRCm39) |
D34E |
probably damaging |
Het |
| Edc4 |
C |
T |
8: 106,614,654 (GRCm39) |
T112I |
possibly damaging |
Het |
| Enpep |
T |
A |
3: 129,106,227 (GRCm39) |
Y333F |
probably damaging |
Het |
| Exoc6 |
A |
G |
19: 37,570,693 (GRCm39) |
H291R |
probably damaging |
Het |
| Fbln5 |
G |
T |
12: 101,731,485 (GRCm39) |
N236K |
probably damaging |
Het |
| Fndc8 |
A |
T |
11: 82,789,555 (GRCm39) |
T238S |
probably damaging |
Het |
| Frem3 |
T |
C |
8: 81,340,917 (GRCm39) |
V1070A |
probably damaging |
Het |
| Gabra4 |
A |
T |
5: 71,729,234 (GRCm39) |
N515K |
possibly damaging |
Het |
| Gemin5 |
A |
G |
11: 58,013,181 (GRCm39) |
V1422A |
possibly damaging |
Het |
| Gm10118 |
A |
G |
10: 63,762,890 (GRCm39) |
|
probably benign |
Het |
| Grm5 |
A |
G |
7: 87,252,281 (GRCm39) |
D177G |
probably damaging |
Het |
| Gtf2h4 |
G |
A |
17: 35,981,792 (GRCm39) |
P147L |
possibly damaging |
Het |
| Hgsnat |
T |
C |
8: 26,453,395 (GRCm39) |
D265G |
probably damaging |
Het |
| Hsd17b4 |
T |
A |
18: 50,310,276 (GRCm39) |
L513Q |
probably damaging |
Het |
| Hsd17b7 |
A |
T |
1: 169,783,487 (GRCm39) |
M307K |
probably benign |
Het |
| Hspa5 |
T |
C |
2: 34,664,629 (GRCm39) |
V361A |
probably damaging |
Het |
| Iqgap2 |
A |
G |
13: 95,768,550 (GRCm39) |
V1450A |
probably benign |
Het |
| Itpr3 |
A |
G |
17: 27,334,039 (GRCm39) |
E2037G |
probably damaging |
Het |
| Itprid2 |
T |
A |
2: 79,488,072 (GRCm39) |
D718E |
probably damaging |
Het |
| Lama5 |
T |
C |
2: 179,835,467 (GRCm39) |
|
probably benign |
Het |
| Manba |
G |
T |
3: 135,230,359 (GRCm39) |
G311* |
probably null |
Het |
| Mettl24 |
T |
A |
10: 40,622,486 (GRCm39) |
V236E |
probably benign |
Het |
| Myh3 |
A |
G |
11: 66,977,201 (GRCm39) |
D310G |
probably damaging |
Het |
| Ncoa4 |
A |
T |
14: 31,888,616 (GRCm39) |
|
probably benign |
Het |
| Nop56 |
G |
T |
2: 130,117,902 (GRCm39) |
R126L |
probably damaging |
Het |
| Nos3 |
C |
A |
5: 24,573,775 (GRCm39) |
|
probably benign |
Het |
| Or13c7b |
T |
C |
4: 43,820,492 (GRCm39) |
M290V |
possibly damaging |
Het |
| Pcdhga3 |
T |
A |
18: 37,809,662 (GRCm39) |
V705D |
probably damaging |
Het |
| Prom2 |
C |
T |
2: 127,371,331 (GRCm39) |
A776T |
possibly damaging |
Het |
| Prss48 |
A |
G |
3: 85,905,492 (GRCm39) |
I127T |
probably damaging |
Het |
| Rtca |
T |
C |
3: 116,293,232 (GRCm39) |
Y193C |
possibly damaging |
Het |
| Samd9l |
T |
C |
6: 3,376,460 (GRCm39) |
Y267C |
probably damaging |
Het |
| Scube3 |
A |
G |
17: 28,379,887 (GRCm39) |
R272G |
possibly damaging |
Het |
| Sprr1a |
G |
T |
3: 92,391,951 (GRCm39) |
H17N |
probably benign |
Het |
| Stard3 |
G |
C |
11: 98,266,361 (GRCm39) |
Q120H |
probably benign |
Het |
| Supt6 |
A |
G |
11: 78,103,574 (GRCm39) |
I1377T |
probably damaging |
Het |
| Svop |
A |
T |
5: 114,203,692 (GRCm39) |
S30T |
probably benign |
Het |
| Syne2 |
T |
A |
12: 76,119,026 (GRCm39) |
L5882* |
probably null |
Het |
| Tanc2 |
G |
T |
11: 105,812,633 (GRCm39) |
R1359L |
probably benign |
Het |
| Tmc7 |
A |
C |
7: 118,165,549 (GRCm39) |
L55R |
probably benign |
Het |
| Trappc11 |
G |
A |
8: 47,972,613 (GRCm39) |
A320V |
probably benign |
Het |
| Ttll8 |
G |
C |
15: 88,818,142 (GRCm39) |
P178A |
probably damaging |
Het |
| Ttn |
T |
C |
2: 76,560,993 (GRCm39) |
E20809G |
probably damaging |
Het |
| Tubb2a |
A |
T |
13: 34,259,451 (GRCm39) |
V113E |
possibly damaging |
Het |
| Ube2d1 |
A |
T |
10: 71,095,699 (GRCm39) |
|
probably benign |
Het |
| Usp48 |
T |
C |
4: 137,343,723 (GRCm39) |
V452A |
probably benign |
Het |
| Vldlr |
T |
A |
19: 27,217,064 (GRCm39) |
I39N |
probably damaging |
Het |
| Wbp1l |
C |
T |
19: 46,642,619 (GRCm39) |
R191* |
probably null |
Het |
| Zyg11b |
C |
T |
4: 108,094,577 (GRCm39) |
W669* |
probably null |
Het |
|
| Other mutations in Chrna4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00815:Chrna4
|
APN |
2 |
180,671,184 (GRCm39) |
missense |
probably benign |
0.09 |
|
IGL00914:Chrna4
|
APN |
2 |
180,670,824 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01511:Chrna4
|
APN |
2 |
180,670,461 (GRCm39) |
missense |
probably benign |
0.13 |
|
IGL02517:Chrna4
|
APN |
2 |
180,670,926 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL02715:Chrna4
|
APN |
2 |
180,671,374 (GRCm39) |
unclassified |
probably benign |
|
|
R1168:Chrna4
|
UTSW |
2 |
180,675,931 (GRCm39) |
missense |
possibly damaging |
0.61 |
|
R1475:Chrna4
|
UTSW |
2 |
180,671,172 (GRCm39) |
missense |
probably benign |
0.44 |
|
R1572:Chrna4
|
UTSW |
2 |
180,671,100 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R4428:Chrna4
|
UTSW |
2 |
180,670,413 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4429:Chrna4
|
UTSW |
2 |
180,670,413 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4431:Chrna4
|
UTSW |
2 |
180,670,413 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4494:Chrna4
|
UTSW |
2 |
180,670,281 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4664:Chrna4
|
UTSW |
2 |
180,679,286 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4666:Chrna4
|
UTSW |
2 |
180,679,286 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4931:Chrna4
|
UTSW |
2 |
180,670,665 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5144:Chrna4
|
UTSW |
2 |
180,666,623 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5556:Chrna4
|
UTSW |
2 |
180,675,773 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R5633:Chrna4
|
UTSW |
2 |
180,671,253 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6056:Chrna4
|
UTSW |
2 |
180,671,235 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6120:Chrna4
|
UTSW |
2 |
180,666,599 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7030:Chrna4
|
UTSW |
2 |
180,671,334 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7352:Chrna4
|
UTSW |
2 |
180,679,267 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7694:Chrna4
|
UTSW |
2 |
180,660,386 (GRCm39) |
missense |
|
|
|
R7945:Chrna4
|
UTSW |
2 |
180,670,454 (GRCm39) |
missense |
probably benign |
0.04 |
|
R8075:Chrna4
|
UTSW |
2 |
180,680,859 (GRCm39) |
missense |
unknown |
|
|
R8706:Chrna4
|
UTSW |
2 |
180,679,307 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9091:Chrna4
|
UTSW |
2 |
180,670,643 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R9138:Chrna4
|
UTSW |
2 |
180,670,775 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R9154:Chrna4
|
UTSW |
2 |
180,670,602 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9270:Chrna4
|
UTSW |
2 |
180,670,643 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R9598:Chrna4
|
UTSW |
2 |
180,679,264 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1177:Chrna4
|
UTSW |
2 |
180,670,078 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
Z1177:Chrna4
|
UTSW |
2 |
180,666,606 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- CAGTACTGGATACTCCGAGACC -3'
(R):5'- GCCCATCTGTGGTCAAAGAC -3'
Sequencing Primer
(F):5'- GAGACCGGCAGCGGATG -3'
(R):5'- TGCCGGAGACTTATCGAATC -3'
|
| Posted On |
2017-02-15 |
Incidental Mutation