Incidental Mutation 'R4428:Chrna4'
ID 328262
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 041698-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.172) question?
Stock # R4428 (G1)
Quality Score 219
Status Validated
Chromosome 2
Chromosomal Location 180664104-180685339 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 180670413 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 448 (S448P)
Ref Sequence ENSEMBL: ENSMUSP00000104479 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000067120] [ENSMUST00000108851]
AlphaFold O70174
Predicted Effect probably damaging
Transcript: ENSMUST00000067120
AA Change: S448P

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000066338
Gene: ENSMUSG00000027577
AA Change: S448P

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 damaging
Transcript: ENSMUST00000108851
AA Change: S448P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000104479
Gene: ENSMUSG00000027577
AA Change: S448P

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
Meta Mutation Damage Score 0.1237 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 20x: 95.5%
Validation Efficiency 100% (46/46)
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
0610040J01Rik G T 5: 64,056,182 (GRCm39) probably benign Het
Abcc1 T A 16: 14,263,164 (GRCm39) V708E probably damaging Het
Bag4 C T 8: 26,259,516 (GRCm39) A228T probably benign Het
Ccdc18 A G 5: 108,283,943 (GRCm39) Y82C probably benign Het
Cd82 T C 2: 93,250,214 (GRCm39) Y266C probably damaging Het
Cldn8 A C 16: 88,359,619 (GRCm39) M102R probably damaging Het
Cmpk1 T C 4: 114,820,559 (GRCm39) E180G probably benign Het
Dock8 T C 19: 25,177,863 (GRCm39) I2066T probably damaging Het
Dock8 T C 19: 25,042,754 (GRCm39) V112A probably benign Het
Fgf3 T C 7: 144,394,444 (GRCm39) V86A probably damaging Het
Frem2 A G 3: 53,561,759 (GRCm39) I916T probably benign Het
Gsk3b T A 16: 38,014,298 (GRCm39) L252Q probably damaging Het
Kif18a A G 2: 109,118,466 (GRCm39) T94A probably damaging Het
Klhdc1 T A 12: 69,315,000 (GRCm39) probably benign Het
Klhl25 T A 7: 75,515,162 (GRCm39) F23I probably damaging Het
Mapk7 T C 11: 61,380,055 (GRCm39) D701G possibly damaging Het
Mbd5 A T 2: 49,169,776 (GRCm39) Q47L possibly damaging Het
Nrcam A G 12: 44,623,558 (GRCm39) D1049G possibly damaging Het
Olfml2a G T 2: 38,831,755 (GRCm39) M111I probably damaging Het
Or3a1c T C 11: 74,046,025 (GRCm39) F15S probably damaging Het
Pld2 A T 11: 70,432,160 (GRCm39) H93L probably damaging Het
Pomgnt2 T C 9: 121,811,320 (GRCm39) E487G possibly damaging Het
Psg17 G T 7: 18,550,717 (GRCm39) N379K probably benign Het
Rfk T A 19: 17,375,959 (GRCm39) H84Q possibly damaging Het
Scn8a A G 15: 100,881,784 (GRCm39) Y617C probably damaging Het
Sema3d T C 5: 12,498,087 (GRCm39) F31S probably benign Het
Shq1 T C 6: 100,647,889 (GRCm39) Y45C probably damaging Het
Siglecg C T 7: 43,067,350 (GRCm39) P639L possibly damaging Het
Skp2 A T 15: 9,117,034 (GRCm39) N325K probably benign Het
Sost G A 11: 101,857,670 (GRCm39) P44S probably damaging Het
Sp8 T A 12: 118,812,938 (GRCm39) S264R possibly damaging Het
Sun1 T C 5: 139,220,230 (GRCm39) probably benign Het
Tardbp A G 4: 148,709,659 (GRCm39) V54A possibly damaging Het
Tert T A 13: 73,775,594 (GRCm39) F115Y probably damaging Het
Tmem181a T A 17: 6,346,061 (GRCm39) L185H probably damaging Het
Tmem68 A T 4: 3,569,534 (GRCm39) I52K probably benign Het
Trhde A T 10: 114,339,028 (GRCm39) L594Q probably damaging Het
Umps A C 16: 33,781,956 (GRCm39) V322G probably damaging Het
Vmn2r109 T C 17: 20,773,286 (GRCm39) D445G probably benign Het
Vmn2r22 T C 6: 123,614,817 (GRCm39) T258A possibly damaging Het
Vmn2r4 C T 3: 64,322,590 (GRCm39) G43E 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
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
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'- CTTGCTCTCAGTCAGGGAAG -3'
(R):5'- CGAATCCATGCACAAGATGG -3'

Sequencing Primer
(F):5'- TCAGGGAAGCAGCTCCATCTTG -3'
(R):5'- TGCACAAGATGGCCAACG -3'
Posted On 2015-07-07