Incidental Mutation 'R4494:Chrna4'
ID 330869
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 041582-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.172) question?
Stock # R4494 (G1)
Quality Score 225
Status Not validated
Chromosome 2
Chromosomal Location 180664104-180685339 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 180670281 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 492 (I492F)
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: I492F

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000066338
Gene: ENSMUSG00000027577
AA Change: I492F

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000108851
AA Change: I492F

PolyPhen 2 Score 0.142 (Sensitivity: 0.92; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000104479
Gene: ENSMUSG00000027577
AA Change: I492F

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
signal peptide 1 30 N/A INTRINSIC
Pfam:Neur_chan_LBD 39 130 9.2e-37 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000198922
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 95.1%
Validation Efficiency
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Atf7ip T A 6: 136,540,747 (GRCm39) probably null Het
Cacna1b T C 2: 24,542,950 (GRCm39) T1301A probably damaging Het
Calcr A T 6: 3,708,484 (GRCm39) probably null Het
Camsap1 T C 2: 25,842,770 (GRCm39) D262G probably damaging Het
Ccdc141 A G 2: 76,962,641 (GRCm39) V101A probably damaging Het
Ccdc170 T C 10: 4,464,128 (GRCm39) Y36H probably damaging Het
Cd177 A T 7: 24,451,428 (GRCm39) S492T probably benign Het
Cit T C 5: 116,012,043 (GRCm39) Y217H probably damaging Het
Cnbd1 T A 4: 19,098,150 (GRCm39) D90V probably benign Het
Cryba2 A G 1: 74,929,789 (GRCm39) F116S probably damaging Het
Ctbp1 T C 5: 33,408,213 (GRCm39) T240A possibly damaging Het
D130043K22Rik C T 13: 25,055,339 (GRCm39) S501L probably benign Het
Ddhd2 A G 8: 26,228,261 (GRCm39) F553S probably benign Het
Ddr2 C A 1: 169,815,983 (GRCm39) G575W probably damaging Het
Dip2c T C 13: 9,621,098 (GRCm39) V537A possibly damaging Het
Dnah12 C T 14: 26,593,812 (GRCm39) A752V probably damaging Het
Dnah7a T C 1: 53,488,197 (GRCm39) D3260G probably benign Het
Efemp2 T A 19: 5,530,339 (GRCm39) C309S probably damaging Het
Gse1 G A 8: 121,297,553 (GRCm39) probably benign Het
Hspa4l T C 3: 40,707,636 (GRCm39) S53P possibly damaging Het
Ighv5-4 T C 12: 113,561,204 (GRCm39) D72G probably benign Het
Igkv15-103 A G 6: 68,414,780 (GRCm39) N73S probably benign Het
Igsf11 T G 16: 38,831,703 (GRCm39) N183K possibly damaging Het
Kcnh8 GAGACCAACGAGCAGCTGATGCTTCAGA GAGA 17: 53,032,934 (GRCm39) 74 probably benign Het
Kcnk18 T C 19: 59,223,263 (GRCm39) V136A probably damaging Het
Krt75 A T 15: 101,480,136 (GRCm39) Y240* probably null Het
Lyst G A 13: 13,809,968 (GRCm39) R546H probably damaging Het
Man2a2 C T 7: 80,009,023 (GRCm39) probably null Het
Mme A G 3: 63,254,613 (GRCm39) N491S probably benign Het
Mrc2 G A 11: 105,239,257 (GRCm39) probably null Het
Msi2 T C 11: 88,608,185 (GRCm39) D39G possibly damaging Het
Naa60 T A 16: 3,718,585 (GRCm39) C122* probably null Het
Nes A G 3: 87,884,120 (GRCm39) E793G probably damaging Het
Nfkb2 A G 19: 46,296,878 (GRCm39) D316G probably damaging Het
Nme6 C T 9: 109,671,122 (GRCm39) L121F probably damaging Het
Or4k47 T A 2: 111,451,493 (GRCm39) K309* probably null Het
Otud1 C T 2: 19,664,146 (GRCm39) T425I probably damaging Het
Pimreg T C 11: 71,935,964 (GRCm39) V149A probably benign Het
Plbd1 T C 6: 136,590,856 (GRCm39) I437V probably damaging Het
Prlhr A T 19: 60,455,519 (GRCm39) M349K probably benign Het
Slc1a3 G A 15: 8,668,579 (GRCm39) T462I probably damaging Het
Slc25a26 A G 6: 94,575,384 (GRCm39) T198A probably damaging Het
Stkld1 A G 2: 26,836,638 (GRCm39) N268S probably benign Het
Svop T C 5: 114,183,688 (GRCm39) T195A probably damaging Het
Syt6 A G 3: 103,492,946 (GRCm39) E66G probably damaging Het
Tas2r129 A G 6: 132,928,317 (GRCm39) I85V probably benign Het
Tent5a A G 9: 85,207,100 (GRCm39) S233P probably damaging Het
Tprn T C 2: 25,158,904 (GRCm39) S643P probably damaging Het
Ush2a C T 1: 188,285,473 (GRCm39) T2003I possibly damaging Het
Vmn2r17 T A 5: 109,576,335 (GRCm39) V402E probably damaging Het
Vmn2r3 C G 3: 64,182,692 (GRCm39) G336R probably damaging Het
Wdr89 A T 12: 75,679,521 (GRCm39) D244E probably damaging Het
Other mutations in Chrna4
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R5889:Chrna4 UTSW 2 180,670,451 (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'- TACTGGACGCCTTCTACTGC -3'
(R):5'- TCCCTGACTTGAAGACATCAG -3'

Sequencing Primer
(F):5'- TCTACTGCCCGTGTCAGG -3'
(R):5'- CCTGACTTGAAGACATCAGAGGTTG -3'
Posted On 2015-07-21