Incidental Mutation 'F0336:Adcy8'
ID 53
Institutional Source Beutler Lab
Gene Symbol Adcy8
Ensembl Gene ENSMUSG00000022376
Gene Name adenylate cyclase 8
Synonyms AC8
Accession Numbers
Essential gene? Probably non essential (E-score: 0.082) question?
Stock # F0336 of strain 468
Quality Score
Status Validated
Chromosome 15
Chromosomal Location 64570884-64794145 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 64694083 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Arginine at position 398 (H398R)
Ref Sequence ENSEMBL: ENSMUSP00000023007 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000023007] [ENSMUST00000180105] [ENSMUST00000228014]
AlphaFold P97490
Predicted Effect probably benign
Transcript: ENSMUST00000023007
AA Change: H398R

PolyPhen 2 Score 0.380 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000023007
Gene: ENSMUSG00000022376
AA Change: H398R

DomainStartEndE-ValueType
low complexity region 52 61 N/A INTRINSIC
low complexity region 111 123 N/A INTRINSIC
low complexity region 185 201 N/A INTRINSIC
low complexity region 255 271 N/A INTRINSIC
CYCc 363 565 3.16e-63 SMART
Pfam:DUF1053 615 710 1.3e-30 PFAM
transmembrane domain 741 759 N/A INTRINSIC
transmembrane domain 780 802 N/A INTRINSIC
transmembrane domain 833 852 N/A INTRINSIC
transmembrane domain 857 879 N/A INTRINSIC
low complexity region 900 911 N/A INTRINSIC
CYCc 940 1155 2.19e-48 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000180105
SMART Domains Protein: ENSMUSP00000136962
Gene: ENSMUSG00000094296

DomainStartEndE-ValueType
low complexity region 60 87 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000228014
AA Change: H398R

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000228109
Meta Mutation Damage Score 0.0664 question?
Coding Region Coverage
  • 1x: 87.7%
  • 3x: 71.5%
Validation Efficiency 92% (54/59)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. The enzymatic activity is under the control of several hormones, and different polypeptides participate in the transduction of the signal from the receptor to the catalytic moiety. Stimulatory or inhibitory receptors (Rs and Ri) interact with G proteins (Gs and Gi) that exhibit GTPase activity and they modulate the activity of the catalytic subunit of the adenylyl cyclase [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutation of this gene results in reduced body size (in female animals only), reduced anxiety, and impaired long term depression (LTD). [provided by MGI curators]
Allele List at MGI

All alleles(1) : Targeted, knock-out(1)

Other mutations in Adcy8
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00589:Adcy8 APN 15 64,659,216 (GRCm39) missense probably damaging 1.00
IGL00690:Adcy8 APN 15 64,571,151 (GRCm39) missense probably damaging 1.00
IGL00990:Adcy8 APN 15 64,694,162 (GRCm39) missense probably benign 0.07
IGL01083:Adcy8 APN 15 64,659,191 (GRCm39) missense probably benign 0.21
IGL01296:Adcy8 APN 15 64,655,628 (GRCm39) missense probably damaging 0.98
IGL01433:Adcy8 APN 15 64,609,263 (GRCm39) missense possibly damaging 0.63
IGL01584:Adcy8 APN 15 64,687,170 (GRCm39) missense probably damaging 1.00
IGL01729:Adcy8 APN 15 64,678,511 (GRCm39) missense probably damaging 1.00
IGL02023:Adcy8 APN 15 64,694,069 (GRCm39) missense probably damaging 1.00
IGL02420:Adcy8 APN 15 64,659,303 (GRCm39) missense probably damaging 1.00
IGL02613:Adcy8 APN 15 64,655,833 (GRCm39) missense possibly damaging 0.82
IGL02662:Adcy8 APN 15 64,618,744 (GRCm39) critical splice donor site probably null
IGL03180:Adcy8 APN 15 64,655,799 (GRCm39) missense possibly damaging 0.77
IGL03327:Adcy8 APN 15 64,792,116 (GRCm39) missense probably damaging 1.00
revolutionary UTSW 15 64,571,236 (GRCm39) missense probably damaging 1.00
whirligig UTSW 15 64,571,134 (GRCm39) missense probably damaging 1.00
K7894:Adcy8 UTSW 15 64,694,083 (GRCm39) missense probably benign 0.38
PIT4581001:Adcy8 UTSW 15 64,626,666 (GRCm39) missense probably damaging 1.00
R0035:Adcy8 UTSW 15 64,571,217 (GRCm39) missense probably benign 0.29
R0119:Adcy8 UTSW 15 64,588,015 (GRCm39) missense probably damaging 1.00
R0129:Adcy8 UTSW 15 64,618,862 (GRCm39) missense probably benign 0.18
R0299:Adcy8 UTSW 15 64,588,015 (GRCm39) missense probably damaging 1.00
R0573:Adcy8 UTSW 15 64,694,044 (GRCm39) missense probably damaging 1.00
R0961:Adcy8 UTSW 15 64,626,711 (GRCm39) missense possibly damaging 0.91
R1203:Adcy8 UTSW 15 64,618,780 (GRCm39) missense probably damaging 1.00
R1239:Adcy8 UTSW 15 64,587,911 (GRCm39) missense probably damaging 0.98
R1615:Adcy8 UTSW 15 64,743,625 (GRCm39) missense probably benign 0.25
R1881:Adcy8 UTSW 15 64,678,503 (GRCm39) missense probably damaging 0.96
R2013:Adcy8 UTSW 15 64,639,727 (GRCm39) missense probably benign 0.00
R2014:Adcy8 UTSW 15 64,639,727 (GRCm39) missense probably benign 0.00
R2015:Adcy8 UTSW 15 64,639,727 (GRCm39) missense probably benign 0.00
R2164:Adcy8 UTSW 15 64,792,783 (GRCm39) missense probably benign
R2228:Adcy8 UTSW 15 64,694,056 (GRCm39) missense possibly damaging 0.58
R2229:Adcy8 UTSW 15 64,694,056 (GRCm39) missense possibly damaging 0.58
R2241:Adcy8 UTSW 15 64,571,230 (GRCm39) missense possibly damaging 0.78
R3177:Adcy8 UTSW 15 64,571,008 (GRCm39) missense probably benign 0.10
R3277:Adcy8 UTSW 15 64,571,008 (GRCm39) missense probably benign 0.10
R3404:Adcy8 UTSW 15 64,571,449 (GRCm39) missense probably damaging 1.00
R3688:Adcy8 UTSW 15 64,743,556 (GRCm39) missense probably damaging 0.99
R3709:Adcy8 UTSW 15 64,597,384 (GRCm39) splice site probably benign
R3710:Adcy8 UTSW 15 64,597,384 (GRCm39) splice site probably benign
R3778:Adcy8 UTSW 15 64,618,846 (GRCm39) missense probably damaging 1.00
R4037:Adcy8 UTSW 15 64,597,319 (GRCm39) missense probably benign 0.06
R4685:Adcy8 UTSW 15 64,609,287 (GRCm39) missense probably benign 0.09
R4731:Adcy8 UTSW 15 64,626,711 (GRCm39) missense possibly damaging 0.91
R4732:Adcy8 UTSW 15 64,626,711 (GRCm39) missense possibly damaging 0.91
R4733:Adcy8 UTSW 15 64,626,711 (GRCm39) missense possibly damaging 0.91
R5071:Adcy8 UTSW 15 64,659,207 (GRCm39) missense probably damaging 1.00
R5073:Adcy8 UTSW 15 64,659,207 (GRCm39) missense probably damaging 1.00
R5074:Adcy8 UTSW 15 64,659,207 (GRCm39) missense probably damaging 1.00
R5091:Adcy8 UTSW 15 64,678,553 (GRCm39) missense probably damaging 1.00
R5285:Adcy8 UTSW 15 64,639,706 (GRCm39) missense possibly damaging 0.68
R5287:Adcy8 UTSW 15 64,588,001 (GRCm39) missense probably benign 0.04
R5403:Adcy8 UTSW 15 64,588,001 (GRCm39) missense probably benign 0.04
R5521:Adcy8 UTSW 15 64,687,199 (GRCm39) missense probably damaging 1.00
R5633:Adcy8 UTSW 15 64,571,134 (GRCm39) missense probably damaging 1.00
R5712:Adcy8 UTSW 15 64,626,715 (GRCm39) missense probably damaging 1.00
R5745:Adcy8 UTSW 15 64,792,320 (GRCm39) missense possibly damaging 0.91
R5787:Adcy8 UTSW 15 64,576,067 (GRCm39) missense probably damaging 0.98
R5839:Adcy8 UTSW 15 64,588,031 (GRCm39) missense probably damaging 1.00
R5890:Adcy8 UTSW 15 64,687,266 (GRCm39) missense probably damaging 1.00
R6156:Adcy8 UTSW 15 64,689,488 (GRCm39) splice site probably null
R6338:Adcy8 UTSW 15 64,792,466 (GRCm39) missense possibly damaging 0.94
R6516:Adcy8 UTSW 15 64,571,236 (GRCm39) missense probably damaging 1.00
R6525:Adcy8 UTSW 15 64,609,243 (GRCm39) nonsense probably null
R6636:Adcy8 UTSW 15 64,659,251 (GRCm39) missense probably damaging 1.00
R6823:Adcy8 UTSW 15 64,626,735 (GRCm39) critical splice acceptor site probably null
R7007:Adcy8 UTSW 15 64,576,565 (GRCm39) missense possibly damaging 0.88
R7070:Adcy8 UTSW 15 64,792,404 (GRCm39) missense probably damaging 1.00
R7092:Adcy8 UTSW 15 64,743,619 (GRCm39) missense possibly damaging 0.93
R7371:Adcy8 UTSW 15 64,571,067 (GRCm39) missense probably benign 0.19
R7457:Adcy8 UTSW 15 64,792,529 (GRCm39) missense possibly damaging 0.79
R7611:Adcy8 UTSW 15 64,792,882 (GRCm39) missense probably benign
R7644:Adcy8 UTSW 15 64,571,218 (GRCm39) missense possibly damaging 0.77
R7697:Adcy8 UTSW 15 64,618,850 (GRCm39) missense probably benign
R7735:Adcy8 UTSW 15 64,655,629 (GRCm39) missense probably benign 0.10
R7789:Adcy8 UTSW 15 64,743,623 (GRCm39) nonsense probably null
R7860:Adcy8 UTSW 15 64,571,322 (GRCm39) missense probably damaging 0.97
R7894:Adcy8 UTSW 15 64,792,054 (GRCm39) missense possibly damaging 0.60
R7948:Adcy8 UTSW 15 64,687,199 (GRCm39) missense possibly damaging 0.80
R7966:Adcy8 UTSW 15 64,573,939 (GRCm39) missense probably damaging 1.00
R8024:Adcy8 UTSW 15 64,792,095 (GRCm39) missense probably damaging 1.00
R8097:Adcy8 UTSW 15 64,743,711 (GRCm39) splice site probably null
R8158:Adcy8 UTSW 15 64,655,655 (GRCm39) missense probably benign 0.32
R8463:Adcy8 UTSW 15 64,792,874 (GRCm39) missense probably benign
R8474:Adcy8 UTSW 15 64,576,638 (GRCm39) missense probably damaging 0.98
R8696:Adcy8 UTSW 15 64,687,235 (GRCm39) missense probably benign 0.30
R8955:Adcy8 UTSW 15 64,576,554 (GRCm39) missense possibly damaging 0.92
R8973:Adcy8 UTSW 15 64,570,984 (GRCm39) makesense probably null
R9015:Adcy8 UTSW 15 64,597,206 (GRCm39) intron probably benign
R9041:Adcy8 UTSW 15 64,609,287 (GRCm39) missense probably benign 0.31
R9052:Adcy8 UTSW 15 64,792,764 (GRCm39) missense probably benign 0.00
R9074:Adcy8 UTSW 15 64,573,940 (GRCm39) missense probably damaging 0.96
R9183:Adcy8 UTSW 15 64,694,116 (GRCm39) missense probably damaging 0.98
R9259:Adcy8 UTSW 15 64,576,604 (GRCm39) missense probably damaging 1.00
R9498:Adcy8 UTSW 15 64,792,045 (GRCm39) missense possibly damaging 0.88
R9522:Adcy8 UTSW 15 64,792,560 (GRCm39) missense probably damaging 0.99
R9800:Adcy8 UTSW 15 64,571,095 (GRCm39) missense probably benign 0.19
Z1176:Adcy8 UTSW 15 64,597,367 (GRCm39) missense probably benign 0.16
Z1177:Adcy8 UTSW 15 64,571,026 (GRCm39) missense probably benign
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 2384 of the Adcy8 transcript, in exon 3 of 18 total exons. The mutated nucleotide causes a histidine to arginine substitution at amino acid 398 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
Adcy8 encodes the 1249 amino acid adenylate cyclase 8 (ADCY8) with evidence at the transcript level. ADCY8 is a twelve-pass membrane protein containing two guanylate cyclase domains that belongs to the adenylyl cyclase class-4/guanylyl cyclase family. These proteins are membrane-bound calcium stimulable adenylyl cyclases that may be involved in learning, memory, and drug dependence. The N- and C-termini of ADCY8 are located in the cytoplasm (Uniprot P97490). A targeted knockout of Adcy8 in mice results in reduced body size (in female animals only), reduced anxiety, and impaired long term depression (LTD).
 
The H398G change is located in the middle cytoplasmic domain of ADCY8, and is predicted to be benign by the PolyPhen program.
Posted On 2009-11-12