Mutagenetix > Incidental Mutation

Incidental Mutation 'D4186:Pde11a'

137

Institutional Source

Beutler Lab

Gene Symbol

Pde11a

Ensembl Gene

ENSMUSG00000075270

Gene Name

phosphodiesterase 11A

Synonyms

A630086N24Rik, 6330414F14Rik

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.135) question?

Stock #

D4186 (G3) of strain 521

Quality Score

Status

Validated

Chromosome

Chromosomal Location

75819485-76169118 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 76121634 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 316 (T316A)

Ref Sequence

ENSEMBL: ENSMUSP00000097572 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000099992]

AlphaFold

P0C1Q2

Predicted Effect

probably damaging
Transcript: ENSMUST00000099992
AA Change: T316A

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000097572
Gene: ENSMUSG00000075270
AA Change: T316A

Domain	Start	End	E-Value	Type
low complexity region	68	82	N/A	INTRINSIC
low complexity region	149	164	N/A	INTRINSIC
GAF	217	380	1.79e-30	SMART
GAF	402	568	2.34e-25	SMART
HDc	661	830	7.75e-6	SMART

Meta Mutation Damage Score

0.3392

Coding Region Coverage

1x: 85.3%
3x: 59.3%

Validation Efficiency

77% (85/111)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele have enlarged lateral ventricles and exhibit abnormal behavior. [provided by MGI curators]

Allele List at MGI

All alleles(2) : Targeted, knock-out(1) Gene trapped(1)

Other mutations in this stock

Total: 6 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ampd2	C	A	3: 107,988,427 (GRCm39)	A11S	probably benign	Het
Clp1	T	C	2: 84,555,979 (GRCm39)	Y167C	probably benign	Homo
Fsip2	T	A	2: 82,818,756 (GRCm39)	S4830T	probably benign	Homo
Patj	T	A	4: 98,526,999 (GRCm39)	S181R	probably benign	Homo
Tango2	G	A	16: 18,130,530 (GRCm39)	R80W	possibly damaging	Het
Ugt2a3	T	C	5: 87,329,613 (GRCm38)	L309R	probably damaging	Het

Other mutations in Pde11a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00839:Pde11a	APN	2	76,045,729 (GRCm39)	missense	probably damaging	1.00
IGL01528:Pde11a	APN	2	76,025,300 (GRCm39)	splice site	probably benign
IGL02117:Pde11a	APN	2	75,821,606 (GRCm39)	missense	probably damaging	1.00
IGL02428:Pde11a	APN	2	75,877,189 (GRCm39)	missense	possibly damaging	0.68
IGL02455:Pde11a	APN	2	75,988,737 (GRCm39)	missense	possibly damaging	0.58
IGL02731:Pde11a	APN	2	75,821,583 (GRCm39)	missense	probably benign	0.00
IGL03068:Pde11a	APN	2	75,848,208 (GRCm39)	missense	probably damaging	1.00
IGL03081:Pde11a	APN	2	75,906,274 (GRCm39)	splice site	probably benign
R0323:Pde11a	UTSW	2	75,877,118 (GRCm39)	splice site	probably null
R0433:Pde11a	UTSW	2	76,168,050 (GRCm39)	missense	possibly damaging	0.47
R1226:Pde11a	UTSW	2	75,988,698 (GRCm39)	missense	probably benign	0.10
R1542:Pde11a	UTSW	2	75,877,199 (GRCm39)	missense	probably benign	0.25
R1941:Pde11a	UTSW	2	76,121,594 (GRCm39)	missense	probably benign	0.10
R2107:Pde11a	UTSW	2	76,168,266 (GRCm39)	missense	probably damaging	1.00
R2394:Pde11a	UTSW	2	75,889,405 (GRCm39)	missense	probably benign	0.00
R3689:Pde11a	UTSW	2	76,121,510 (GRCm39)	missense	probably damaging	1.00
R3690:Pde11a	UTSW	2	76,121,510 (GRCm39)	missense	probably damaging	1.00
R3945:Pde11a	UTSW	2	75,906,275 (GRCm39)	splice site	probably benign
R4073:Pde11a	UTSW	2	76,168,242 (GRCm39)	missense	probably damaging	1.00
R4074:Pde11a	UTSW	2	76,168,242 (GRCm39)	missense	probably damaging	1.00
R4588:Pde11a	UTSW	2	75,859,647 (GRCm39)	missense	probably damaging	1.00
R4602:Pde11a	UTSW	2	75,988,677 (GRCm39)	missense	probably benign	0.05
R4604:Pde11a	UTSW	2	76,168,137 (GRCm39)	missense	possibly damaging	0.89
R4609:Pde11a	UTSW	2	76,121,585 (GRCm39)	missense	possibly damaging	0.94
R4610:Pde11a	UTSW	2	75,988,677 (GRCm39)	missense	probably benign	0.05
R5017:Pde11a	UTSW	2	75,966,711 (GRCm39)	missense	probably benign	0.05
R5519:Pde11a	UTSW	2	75,906,299 (GRCm39)	missense	probably damaging	1.00
R5930:Pde11a	UTSW	2	75,970,175 (GRCm39)	splice site	probably null
R6000:Pde11a	UTSW	2	75,848,204 (GRCm39)	missense	probably damaging	0.98
R6018:Pde11a	UTSW	2	75,848,194 (GRCm39)	missense	probably benign	0.00
R6913:Pde11a	UTSW	2	76,168,084 (GRCm39)	missense	probably damaging	1.00
R7117:Pde11a	UTSW	2	75,906,348 (GRCm39)	missense	probably damaging	1.00
R7258:Pde11a	UTSW	2	75,970,250 (GRCm39)	missense	possibly damaging	0.91
R7267:Pde11a	UTSW	2	76,168,189 (GRCm39)	missense	probably damaging	1.00
R7409:Pde11a	UTSW	2	75,836,328 (GRCm39)	missense
R7451:Pde11a	UTSW	2	75,853,117 (GRCm39)	missense	possibly damaging	0.89
R7452:Pde11a	UTSW	2	75,966,758 (GRCm39)	missense	probably damaging	1.00
R7598:Pde11a	UTSW	2	75,966,767 (GRCm39)	missense	probably damaging	1.00
R7671:Pde11a	UTSW	2	76,045,697 (GRCm39)	missense	possibly damaging	0.81
R7886:Pde11a	UTSW	2	76,121,547 (GRCm39)	missense	probably benign
R8045:Pde11a	UTSW	2	75,853,072 (GRCm39)	missense	probably damaging	0.99
R8137:Pde11a	UTSW	2	76,041,383 (GRCm39)	missense	possibly damaging	0.91
R8420:Pde11a	UTSW	2	75,889,354 (GRCm39)	missense	probably damaging	1.00
R8716:Pde11a	UTSW	2	75,848,238 (GRCm39)	missense	probably damaging	0.97
R8730:Pde11a	UTSW	2	75,889,334 (GRCm39)	missense	probably damaging	1.00
R8816:Pde11a	UTSW	2	76,121,577 (GRCm39)	missense	probably benign	0.00
R8869:Pde11a	UTSW	2	76,041,434 (GRCm39)	missense	probably benign	0.02
R9023:Pde11a	UTSW	2	75,966,803 (GRCm39)	missense	probably damaging	1.00
R9202:Pde11a	UTSW	2	75,853,077 (GRCm39)	nonsense	probably null
R9301:Pde11a	UTSW	2	75,848,217 (GRCm39)	missense	probably damaging	1.00
R9470:Pde11a	UTSW	2	75,821,612 (GRCm39)	missense	probably benign
R9570:Pde11a	UTSW	2	75,877,157 (GRCm39)	missense	probably damaging	1.00
R9728:Pde11a	UTSW	2	76,121,608 (GRCm39)	missense	probably damaging	1.00
Z1176:Pde11a	UTSW	2	76,025,249 (GRCm39)	missense	probably benign	0.01

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 992 of the Pde11a transcript in exon 2 of 20 total exons. Multiple transcripts of the Pde11a gene are displayed on Ensembl. The mutated nucleotide causes a threonine to alanine substitution at amino acid 316 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Pde11a gene encodes a 933 amino acid protein that is a dual 3',5'-cyclic-AMP and -GMP phosphodiesterase. PDE11A can catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provides a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene in humans are a cause of Cushing disease and adrenocortical hyperplasia.

The T316A change occurs in a domain that is found in cGMP phosphodiesterases (SMART), and is predicted to be probably damaging by the PolyPhen program.

Posted On

2010-03-19