Mutagenetix > Incidental Mutation

Incidental Mutation 'R0015:Adcy3'

8273

Institutional Source

Beutler Lab

Gene Symbol

Adcy3

Ensembl Gene

ENSMUSG00000020654

Gene Name

adenylate cyclase 3

Synonyms

AC3, ACIII

MMRRC Submission

038310-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.859) question?

Stock #

R0015 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

4183397-4263525 bp(+) (GRCm39)

Type of Mutation

critical splice donor site (1 bp from exon)

DNA Base Change (assembly)

G to A at 4245260 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000115644 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020984] [ENSMUST00000111169] [ENSMUST00000124505] [ENSMUST00000127756] [ENSMUST00000127756] [ENSMUST00000152065]

AlphaFold

Q8VHH7

Predicted Effect

probably null
Transcript: ENSMUST00000020984

SMART Domains

Protein: ENSMUSP00000020984
Gene: ENSMUSG00000020654

Domain	Start	End	E-Value	Type
low complexity region	11	21	N/A	INTRINSIC
transmembrane domain	78	100	N/A	INTRINSIC
transmembrane domain	105	125	N/A	INTRINSIC
transmembrane domain	138	160	N/A	INTRINSIC
transmembrane domain	170	187	N/A	INTRINSIC
transmembrane domain	189	211	N/A	INTRINSIC
transmembrane domain	226	245	N/A	INTRINSIC
CYCc	270	472	2.17e-61	SMART
low complexity region	516	526	N/A	INTRINSIC
low complexity region	535	554	N/A	INTRINSIC
coiled coil region	567	600	N/A	INTRINSIC
transmembrane domain	631	650	N/A	INTRINSIC
transmembrane domain	660	682	N/A	INTRINSIC
transmembrane domain	710	732	N/A	INTRINSIC
transmembrane domain	752	771	N/A	INTRINSIC
transmembrane domain	776	798	N/A	INTRINSIC
transmembrane domain	841	858	N/A	INTRINSIC
CYCc	884	1103	2.02e-70	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000111169

SMART Domains

Protein: ENSMUSP00000106799
Gene: ENSMUSG00000020652

Domain	Start	End	E-Value	Type
coiled coil region	39	74	N/A	INTRINSIC
Pfam:CENP-O	118	195	2.1e-19	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000124505

SMART Domains

Protein: ENSMUSP00000122073
Gene: ENSMUSG00000020654

Domain	Start	End	E-Value	Type
low complexity region	11	21	N/A	INTRINSIC
transmembrane domain	78	100	N/A	INTRINSIC
transmembrane domain	105	125	N/A	INTRINSIC
transmembrane domain	138	160	N/A	INTRINSIC
transmembrane domain	170	187	N/A	INTRINSIC
transmembrane domain	189	211	N/A	INTRINSIC
transmembrane domain	226	245	N/A	INTRINSIC
CYCc	270	472	2.17e-61	SMART
low complexity region	516	526	N/A	INTRINSIC
low complexity region	535	554	N/A	INTRINSIC
coiled coil region	567	600	N/A	INTRINSIC
transmembrane domain	631	650	N/A	INTRINSIC
transmembrane domain	660	682	N/A	INTRINSIC
transmembrane domain	710	732	N/A	INTRINSIC
transmembrane domain	752	771	N/A	INTRINSIC
transmembrane domain	776	798	N/A	INTRINSIC
transmembrane domain	840	857	N/A	INTRINSIC
CYCc	883	1102	2.02e-70	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000127756

SMART Domains

Protein: ENSMUSP00000115406
Gene: ENSMUSG00000020654

Domain	Start	End	E-Value	Type
low complexity region	11	21	N/A	INTRINSIC
low complexity region	78	88	N/A	INTRINSIC
low complexity region	183	197	N/A	INTRINSIC
CYCc	270	472	2.17e-61	SMART
low complexity region	516	526	N/A	INTRINSIC
low complexity region	535	554	N/A	INTRINSIC
coiled coil region	567	600	N/A	INTRINSIC
transmembrane domain	631	650	N/A	INTRINSIC
transmembrane domain	660	682	N/A	INTRINSIC
transmembrane domain	710	732	N/A	INTRINSIC
transmembrane domain	752	771	N/A	INTRINSIC
transmembrane domain	776	798	N/A	INTRINSIC
transmembrane domain	841	858	N/A	INTRINSIC
CYCc	884	1103	2.02e-70	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000127756

SMART Domains

Protein: ENSMUSP00000115406
Gene: ENSMUSG00000020654

Domain	Start	End	E-Value	Type
low complexity region	11	21	N/A	INTRINSIC
low complexity region	78	88	N/A	INTRINSIC
low complexity region	183	197	N/A	INTRINSIC
CYCc	270	472	2.17e-61	SMART
low complexity region	516	526	N/A	INTRINSIC
low complexity region	535	554	N/A	INTRINSIC
coiled coil region	567	600	N/A	INTRINSIC
transmembrane domain	631	650	N/A	INTRINSIC
transmembrane domain	660	682	N/A	INTRINSIC
transmembrane domain	710	732	N/A	INTRINSIC
transmembrane domain	752	771	N/A	INTRINSIC
transmembrane domain	776	798	N/A	INTRINSIC
transmembrane domain	841	858	N/A	INTRINSIC
CYCc	884	1103	2.02e-70	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000146261

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150944

Predicted Effect

probably null
Transcript: ENSMUST00000152065

SMART Domains

Protein: ENSMUSP00000115644
Gene: ENSMUSG00000020654

Domain	Start	End	E-Value	Type
low complexity region	11	21	N/A	INTRINSIC
transmembrane domain	78	100	N/A	INTRINSIC
transmembrane domain	105	125	N/A	INTRINSIC
transmembrane domain	138	160	N/A	INTRINSIC
transmembrane domain	170	187	N/A	INTRINSIC
transmembrane domain	189	211	N/A	INTRINSIC
transmembrane domain	226	245	N/A	INTRINSIC
CYCc	270	472	2.17e-61	SMART
low complexity region	516	526	N/A	INTRINSIC
low complexity region	535	554	N/A	INTRINSIC
coiled coil region	567	600	N/A	INTRINSIC
transmembrane domain	631	650	N/A	INTRINSIC
transmembrane domain	660	682	N/A	INTRINSIC
transmembrane domain	710	732	N/A	INTRINSIC
transmembrane domain	752	771	N/A	INTRINSIC
transmembrane domain	776	798	N/A	INTRINSIC
transmembrane domain	840	857	N/A	INTRINSIC
CYCc	883	1102	2.02e-70	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000152792

Meta Mutation Damage Score

0.9586

Coding Region Coverage

1x: 80.5%
3x: 72.2%
10x: 49.0%
20x: 28.4%

Validation Efficiency

90% (88/98)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
PHENOTYPE: Mice homozygous for one mutation of this gene display impaired olfaction and disorganization of glomeruli in the main olfactory bulb. Mutant animals also appear to be sterile as homozygous matings failed to produce litters. Mice with another mutant allele fail to survive beyond weaning. [provided by MGI curators]

Allele List at MGI

All alleles(9) : Targeted(4) Gene trapped(5)

Other mutations in this stock

Total: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A130050O07Rik	A	G	1: 137,856,394 (GRCm39)	Y23C	unknown	Het
Aadat	C	T	8: 60,987,605 (GRCm39)		probably benign	Het
Armc3	A	G	2: 19,301,132 (GRCm39)		probably null	Het
Astn2	T	G	4: 66,184,619 (GRCm39)		probably null	Het
Borcs8	T	C	8: 70,593,017 (GRCm39)		probably benign	Het
Cacna1d	G	A	14: 29,836,928 (GRCm39)	T804I	probably benign	Het
Card19	A	G	13: 49,361,532 (GRCm39)	L33P	probably benign	Het
Ccny	A	C	18: 9,316,682 (GRCm39)		probably benign	Het
Cdh5	C	T	8: 104,867,559 (GRCm39)	T612I	probably benign	Het
Cfap58	A	G	19: 48,017,539 (GRCm39)	M800V	probably benign	Het
Clrn1	A	T	3: 58,753,848 (GRCm39)	I171K	probably damaging	Het
Cnp	T	A	11: 100,469,734 (GRCm39)		probably null	Het
Col12a1	T	C	9: 79,558,667 (GRCm39)	T1933A	probably damaging	Het
Cplane1	G	A	15: 8,215,668 (GRCm39)	R408H	probably damaging	Het
Cwf19l2	A	G	9: 3,454,666 (GRCm39)	S660G	probably benign	Het
Dync1i2	C	A	2: 71,044,828 (GRCm39)	R13S	probably damaging	Het
Fat4	T	A	3: 39,036,652 (GRCm39)	S3435T	probably damaging	Het
Fchsd1	A	G	18: 38,096,012 (GRCm39)	C533R	probably benign	Het
Fstl5	G	A	3: 76,229,498 (GRCm39)	V100M	probably damaging	Het
Gria2	C	T	3: 80,615,074 (GRCm39)	G469S	probably damaging	Het
Hsf5	C	A	11: 87,548,161 (GRCm39)	H615N	probably benign	Het
Ints2	T	C	11: 86,140,113 (GRCm39)	T240A	probably damaging	Het
Kcnn3	A	C	3: 89,570,080 (GRCm39)	D631A	probably damaging	Het
Lama4	C	T	10: 38,951,432 (GRCm39)	T1059M	possibly damaging	Het
Lgals8	A	G	13: 12,462,179 (GRCm39)	L226P	probably damaging	Het
Lonp1	T	A	17: 56,925,406 (GRCm39)	Q462L	probably benign	Het
Mark2	A	T	19: 7,263,142 (GRCm39)	Y231*	probably null	Het
Mdh1b	T	C	1: 63,760,959 (GRCm39)		probably benign	Het
Myh7b	C	T	2: 155,464,206 (GRCm39)	P569L	probably damaging	Het
Myl3	A	C	9: 110,596,997 (GRCm39)	D119A	probably damaging	Het
Ncapd3	C	A	9: 26,963,105 (GRCm39)	A470E	probably damaging	Het
Ndrg2	A	G	14: 52,147,902 (GRCm39)		probably benign	Het
Nprl2	A	T	9: 107,421,618 (GRCm39)	I209F	probably damaging	Het
Pcf11	T	A	7: 92,307,525 (GRCm39)	H881L	probably benign	Het
Pde10a	A	G	17: 9,196,029 (GRCm39)	D640G	probably damaging	Het
Pdxdc1	A	T	16: 13,705,547 (GRCm39)		probably benign	Het
Polr2g	A	G	19: 8,771,016 (GRCm39)	I160T	probably damaging	Het
Pter	G	A	2: 13,005,811 (GRCm39)	G328D	probably damaging	Het
Rad51	T	A	2: 118,946,808 (GRCm39)	M5K	probably benign	Het
Rbm43	T	A	2: 51,815,679 (GRCm39)	I181F	probably benign	Het
Rgs12	T	C	5: 35,180,120 (GRCm39)		probably benign	Het
Slc20a2	C	A	8: 23,025,361 (GRCm39)	A21E	probably damaging	Het
Sybu	T	C	15: 44,536,896 (GRCm39)	R349G	probably damaging	Het
Tmem161b	C	A	13: 84,370,533 (GRCm39)		probably null	Het
Xirp2	C	A	2: 67,341,243 (GRCm39)	Y1161*	probably null	Het
Zfand4	C	A	6: 116,305,258 (GRCm39)	T705K	probably damaging	Het

Other mutations in Adcy3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00427:Adcy3	APN	12	4,244,357 (GRCm39)	missense	probably damaging	1.00
IGL00985:Adcy3	APN	12	4,184,600 (GRCm39)	missense	probably damaging	0.98
IGL01735:Adcy3	APN	12	4,251,213 (GRCm39)	missense	probably benign	0.00
IGL02097:Adcy3	APN	12	4,262,118 (GRCm39)	missense	probably damaging	1.00
IGL02102:Adcy3	APN	12	4,184,699 (GRCm39)	missense	probably damaging	1.00
IGL02103:Adcy3	APN	12	4,184,390 (GRCm39)	missense	possibly damaging	0.69
IGL02155:Adcy3	APN	12	4,262,142 (GRCm39)	nonsense	probably null
IGL02376:Adcy3	APN	12	4,251,031 (GRCm39)	missense	possibly damaging	0.77
IGL02411:Adcy3	APN	12	4,259,407 (GRCm39)	splice site	probably null
IGL02465:Adcy3	APN	12	4,250,906 (GRCm39)	missense	probably benign	0.10
IGL02819:Adcy3	APN	12	4,256,986 (GRCm39)	splice site	probably benign
magnificent_frigatebird	UTSW	12	4,244,324 (GRCm39)	missense	probably damaging	1.00
R0015:Adcy3	UTSW	12	4,245,260 (GRCm39)	critical splice donor site	probably null
R0918:Adcy3	UTSW	12	4,248,360 (GRCm39)	missense	probably benign	0.05
R1480:Adcy3	UTSW	12	4,262,171 (GRCm39)	missense	probably damaging	1.00
R1736:Adcy3	UTSW	12	4,250,998 (GRCm39)	missense	possibly damaging	0.87
R1885:Adcy3	UTSW	12	4,184,951 (GRCm39)	missense	probably damaging	1.00
R1897:Adcy3	UTSW	12	4,223,450 (GRCm39)	splice site	probably benign
R1951:Adcy3	UTSW	12	4,258,624 (GRCm39)	missense	probably benign	0.29
R2083:Adcy3	UTSW	12	4,223,512 (GRCm39)	missense	probably damaging	1.00
R2417:Adcy3	UTSW	12	4,258,627 (GRCm39)	missense	probably benign	0.05
R4379:Adcy3	UTSW	12	4,184,558 (GRCm39)	missense	probably damaging	1.00
R4785:Adcy3	UTSW	12	4,256,542 (GRCm39)	missense	probably benign	0.00
R4960:Adcy3	UTSW	12	4,184,896 (GRCm39)	missense	probably benign	0.11
R5001:Adcy3	UTSW	12	4,248,434 (GRCm39)	missense	possibly damaging	0.56
R5166:Adcy3	UTSW	12	4,184,438 (GRCm39)	missense	probably damaging	1.00
R5375:Adcy3	UTSW	12	4,260,870 (GRCm39)	missense	probably damaging	1.00
R5416:Adcy3	UTSW	12	4,259,308 (GRCm39)	missense	probably damaging	1.00
R5998:Adcy3	UTSW	12	4,248,348 (GRCm39)	missense	probably damaging	1.00
R6248:Adcy3	UTSW	12	4,258,662 (GRCm39)	critical splice donor site	probably null
R6490:Adcy3	UTSW	12	4,262,150 (GRCm39)	missense	probably damaging	1.00
R6566:Adcy3	UTSW	12	4,244,324 (GRCm39)	missense	probably damaging	1.00
R7145:Adcy3	UTSW	12	4,250,992 (GRCm39)	missense	probably benign	0.20
R7283:Adcy3	UTSW	12	4,253,563 (GRCm39)	missense	not run
R7559:Adcy3	UTSW	12	4,248,440 (GRCm39)	missense	probably benign	0.06
R7691:Adcy3	UTSW	12	4,256,540 (GRCm39)	missense	probably benign	0.17
R7799:Adcy3	UTSW	12	4,254,762 (GRCm39)	missense	probably damaging	1.00
R8074:Adcy3	UTSW	12	4,184,420 (GRCm39)	missense	probably benign	0.00
R8283:Adcy3	UTSW	12	4,250,935 (GRCm39)	missense	probably damaging	1.00
R8298:Adcy3	UTSW	12	4,256,482 (GRCm39)	missense	probably damaging	1.00
R8515:Adcy3	UTSW	12	4,262,187 (GRCm39)	missense	probably damaging	1.00
R9145:Adcy3	UTSW	12	4,245,208 (GRCm39)	missense	probably damaging	0.99
R9361:Adcy3	UTSW	12	4,259,366 (GRCm39)	missense	possibly damaging	0.80
R9464:Adcy3	UTSW	12	4,256,939 (GRCm39)	missense	probably benign
R9643:Adcy3	UTSW	12	4,259,455 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

ADCY3 is an olfactory type cyclase that, in olfactory neurons, is activated through the G protein G_olf expressed in the olfactory epithelium (1-6); intracellular cAMP is increased. The increased cAMP levels subsequently activates the cyclic nucleotide gated channel (CNG) (7), which in turn causes membrane depolarization and generation of an action potential (4). It is proposed that the olfactory-like signaling pathway (including ADCY3) is involved in spermatogenesis and spermatozoa functions (3).

Expression/Localization

ADCY3 is ubiquitously expressed with highest expression in lung, testis, ovary, and colon and placenta, intermediate expression in brain, heart, kidney, and skeletal muscle, and lowest expression in liver and pancreas (8;9). Isolated pancreatic islet mRNA also showed high expression (8). In rat, AC3 mRNA is expressed in rat spermatids with the protein localized in the acrosomal region of spermatids (1;2).

Background

Adcy3^{tm1Drs/tm1Drs}; MGI:2661086

involves: 129X1/SvJ * C57BL/6

Homozygous animals are partially postnatal lethal and are initially smaller than wild-type littermates (5). These mice demonstrate anosmia (i.e., the inability to detect an odorant) toward both IP₃- and cAMP-generating odorants and fail olfactory-dependent behavioral assays (5). Homozygous matings do not produce litters (5) and have reduced fertility (3).

Adcy3^{tm1Dgen/tm1Dgen}; MGI:3604495

involves: 129P2/OlaHsd * C57BL/6

Homozygous animals fail to survive past weaning.

References

1. Gautier-Courteille, C., Salanova, M., and Conti, M. (1998) The Olfactory Adenylyl Cyclase III is Expressed in Rat Germ Cells during Spermiogenesis. Endocrinology. 139, 2588-2599.

2. Defer, N., Marinx, O., Poyard, M., Lienard, M. O., Jegou, B., and Hanoune, J. (1998) The Olfactory Adenylyl Cyclase Type 3 is Expressed in Male Germ Cells. FEBS Lett. 424, 216-220.

3. Livera, G., Xie, F., Garcia, M. A., Jaiswal, B., Chen, J., Law, E., Storm, D. R., and Conti, M. (2005) Inactivation of the Mouse Adenylyl Cyclase 3 Gene Disrupts Male Fertility and Spermatozoon Function. Mol Endocrinol. 19, 1277-1290.

4. Trinh, K., and Storm, D. R. (2003) Vomeronasal Organ Detects Odorants in Absence of Signaling through Main Olfactory Epithelium. Nat Neurosci. 6, 519-525.

5. Wong, S. T., Trinh, K., Hacker, B., Chan, G. C., Lowe, G., Gaggar, A., Xia, Z., Gold, G. H., and Storm, D. R. (2000) Disruption of the Type III Adenylyl Cyclase Gene Leads to Peripheral and Behavioral Anosmia in Transgenic Mice. Neuron. 27, 487-497.

6. Wei, J., Zhao, A. Z., Chan, G. C., Baker, L. P., Impey, S., Beavo, J. A., and Storm, D. R. (1998) Phosphorylation and Inhibition of Olfactory Adenylyl Cyclase by CaM Kinase II in Neurons: A Mechanism for Attenuation of Olfactory Signals. Neuron. 21, 495-504.

7. Dhallan, R. S., Yau, K. W., Schrader, K. A., and Reed, R. R. (1990) Primary Structure and Functional Expression of a Cyclic Nucleotide-Activated Channel from Olfactory Neurons. Nature. 347, 184-187.

8. Yang, B., He, B., Abdel-Halim, S. M., Tibell, A., Brendel, M. D., Bretzel, R. G., Efendic, S., and Hillert, J. (1999) Molecular Cloning of a Full-Length cDNA for Human Type 3 Adenylyl Cyclase and its Expression in Human Islets. Biochem Biophys Res Commun. 254, 548-551.

9. Ludwig, M. G., and Seuwen, K. (2002) Characterization of the Human Adenylyl Cyclase Gene Family: CDNA, Gene Structure, and Tissue Distribution of the Nine Isoforms. J Recept Signal Transduct Res. 22, 79-110.

Posted On

2012-11-21

Science Writer

Anne Murray