Mutagenetix > Incidental Mutation

Incidental Mutation 'A9681:Pakap'

Institutional Source

Beutler Lab

Gene Symbol

Pakap

Ensembl Gene

ENSMUSG00000089945

Gene Name

paralemmin A kinase anchor protein

Synonyms

Palm2-Akap2, Akap2, AKAP-KL, Palm2Akap2, Gm20459, AF064781, B230340M18Rik, 53-H12, pEN70, Palm2

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.128) question?

Stock #

A9681 (G3) of strain atchoum

Quality Score

Status

Validated

Chromosome

Chromosomal Location

57434475-57896984 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 57855358 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 270 (Q270R)

Ref Sequence

ENSEMBL: ENSMUSP00000103226 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000043456] [ENSMUST00000098064] [ENSMUST00000098066] [ENSMUST00000102902] [ENSMUST00000102903] [ENSMUST00000107598] [ENSMUST00000107600] [ENSMUST00000132497] [ENSMUST00000124581] [ENSMUST00000126465]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000043456
AA Change: Q229R

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000048678
Gene: ENSMUSG00000038729
AA Change: Q229R

Domain	Start	End	E-Value	Type
low complexity region	152	163	N/A	INTRINSIC
low complexity region	213	227	N/A	INTRINSIC
coiled coil region	256	314	N/A	INTRINSIC
Pfam:AKAP2_C	568	885	2.5e-17	PFAM
Pfam:RII_binding_1	585	602	1.6e-5	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000098064
AA Change: Q229R

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000095672
Gene: ENSMUSG00000038729
AA Change: Q229R

Domain	Start	End	E-Value	Type
low complexity region	152	163	N/A	INTRINSIC
low complexity region	213	227	N/A	INTRINSIC
coiled coil region	256	314	N/A	INTRINSIC
Pfam:AKAP2_C	569	872	4e-13	PFAM
Pfam:RII_binding_1	585	602	2.9e-5	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000098065

Predicted Effect

probably benign
Transcript: ENSMUST00000098066

SMART Domains

Protein: ENSMUSP00000095674
Gene: ENSMUSG00000089945

Domain	Start	End	E-Value	Type
Pfam:Paralemmin	67	138	6.3e-23	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000102902
AA Change: Q229R

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000099966
Gene: ENSMUSG00000038729
AA Change: Q229R

Domain	Start	End	E-Value	Type
low complexity region	152	163	N/A	INTRINSIC
low complexity region	213	227	N/A	INTRINSIC
coiled coil region	256	314	N/A	INTRINSIC
Pfam:RII_binding_1	585	602	3.5e-5	PFAM
coiled coil region	730	766	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000102903
AA Change: Q229R

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000099967
Gene: ENSMUSG00000038729
AA Change: Q229R

Domain	Start	End	E-Value	Type
low complexity region	152	163	N/A	INTRINSIC
low complexity region	213	227	N/A	INTRINSIC
coiled coil region	256	314	N/A	INTRINSIC
Pfam:RII_binding_1	585	602	3.5e-5	PFAM
coiled coil region	730	766	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000107598
AA Change: Q229R

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000103224
Gene: ENSMUSG00000038729
AA Change: Q229R

Domain	Start	End	E-Value	Type
low complexity region	152	163	N/A	INTRINSIC
low complexity region	213	227	N/A	INTRINSIC
coiled coil region	256	314	N/A	INTRINSIC
Pfam:AKAP2_C	569	872	4e-13	PFAM
Pfam:RII_binding_1	585	602	2.9e-5	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000107600
AA Change: Q270R

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000103226
Gene: ENSMUSG00000038729
AA Change: Q270R

Domain	Start	End	E-Value	Type
low complexity region	193	204	N/A	INTRINSIC
low complexity region	254	268	N/A	INTRINSIC
coiled coil region	297	355	N/A	INTRINSIC
Pfam:AKAP2_C	636	913	2.8e-12	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000150412
AA Change: Q472R

SMART Domains

Protein: ENSMUSP00000117466
Gene: ENSMUSG00000089945
AA Change: Q472R

Domain	Start	End	E-Value	Type
low complexity region	15	28	N/A	INTRINSIC
low complexity region	35	59	N/A	INTRINSIC
Pfam:Paralemmin	115	269	6.5e-23	PFAM
low complexity region	396	407	N/A	INTRINSIC
low complexity region	457	471	N/A	INTRINSIC
coiled coil region	499	557	N/A	INTRINSIC
Pfam:AKAP2_C	847	1129	1.9e-17	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000132497

Predicted Effect

probably benign
Transcript: ENSMUST00000124581

SMART Domains

Protein: ENSMUSP00000119742
Gene: ENSMUSG00000038729

Domain	Start	End	E-Value	Type
low complexity region	152	163	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000126465

SMART Domains

Protein: ENSMUSP00000130230
Gene: ENSMUSG00000089945

Domain	Start	End	E-Value	Type
Pfam:Paralemmin	67	138	6.3e-23	PFAM

Meta Mutation Damage Score

0.1092

Coding Region Coverage

1x: 85.7%
3x: 64.9%

Validation Efficiency

85% (88/103)

MGI Phenotype

FUNCTION: This locus represents naturally occurring readthrough transcription between the neighboring Palm2 (paralemmin 2) and Akap2 (A kinase (PRKA) anchor protein 2) genes on chromosome 4. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. Similar readthrough transcription has also been observed in human, as described in PMID: 11478809. [provided by RefSeq, Feb 2015]

Allele List at MGI

Other mutations in this stock

Total: 5 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ablim1	A	G	19: 57,161,755 (GRCm39)		probably null	Homo
Gm9943	T	A	17: 16,235,254 (GRCm39)			Het
Ints1	T	C	5: 139,755,894 (GRCm39)	E538G	possibly damaging	Homo
Or52n1	T	C	7: 104,383,610 (GRCm39)		probably benign	Het
Pld1	C	A	3: 28,139,981 (GRCm39)	H600Q	probably benign	Homo

Other mutations in Pakap

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01123:Pakap	APN	4	57,757,627 (GRCm39)	nonsense	probably null
IGL01371:Pakap	APN	4	57,856,325 (GRCm39)	missense	probably benign	0.03
IGL01647:Pakap	APN	4	57,688,477 (GRCm39)	missense	possibly damaging	0.82
IGL01733:Pakap	APN	4	57,856,488 (GRCm39)	missense	probably benign	0.01
IGL02677:Pakap	APN	4	57,856,263 (GRCm39)	missense	probably benign	0.01
IGL02696:Pakap	APN	4	57,854,663 (GRCm39)	missense	probably damaging	0.97
IGL02736:Pakap	APN	4	57,709,721 (GRCm39)	missense	probably damaging	0.96
IGL03067:Pakap	APN	4	57,648,038 (GRCm39)	missense	probably benign	0.02
IGL03343:Pakap	APN	4	57,688,502 (GRCm39)	missense	probably damaging	1.00
IGL02835:Pakap	UTSW	4	57,883,044 (GRCm39)	missense	probably damaging	1.00
PIT4305001:Pakap	UTSW	4	57,638,029 (GRCm39)	missense	possibly damaging	0.94
R0158:Pakap	UTSW	4	57,709,649 (GRCm39)	missense	possibly damaging	0.96
R0244:Pakap	UTSW	4	57,710,177 (GRCm39)	missense	possibly damaging	0.74
R0284:Pakap	UTSW	4	57,855,207 (GRCm39)	missense	probably damaging	1.00
R0356:Pakap	UTSW	4	57,855,628 (GRCm39)	missense	possibly damaging	0.48
R0594:Pakap	UTSW	4	57,856,752 (GRCm39)	missense	probably benign	0.00
R0614:Pakap	UTSW	4	57,856,720 (GRCm39)	missense	probably benign	0.41
R0617:Pakap	UTSW	4	57,829,434 (GRCm39)	intron	probably benign
R0763:Pakap	UTSW	4	57,688,441 (GRCm39)	missense	probably damaging	1.00
R0800:Pakap	UTSW	4	57,709,650 (GRCm39)	missense	probably benign	0.06
R1228:Pakap	UTSW	4	57,856,909 (GRCm39)	missense	probably damaging	1.00
R1861:Pakap	UTSW	4	57,709,468 (GRCm39)	missense	probably damaging	0.97
R1895:Pakap	UTSW	4	57,638,068 (GRCm39)	missense	probably benign	0.01
R1913:Pakap	UTSW	4	57,892,963 (GRCm39)	missense	probably damaging	1.00
R2081:Pakap	UTSW	4	57,855,927 (GRCm39)	missense	possibly damaging	0.49
R2128:Pakap	UTSW	4	57,854,890 (GRCm39)	missense	probably benign	0.40
R2339:Pakap	UTSW	4	57,883,180 (GRCm39)	missense	probably damaging	1.00
R4600:Pakap	UTSW	4	57,709,954 (GRCm39)	missense	probably benign	0.26
R4667:Pakap	UTSW	4	57,855,655 (GRCm39)	missense	possibly damaging	0.80
R4804:Pakap	UTSW	4	57,854,688 (GRCm39)	missense	probably benign	0.05
R4989:Pakap	UTSW	4	57,856,552 (GRCm39)	missense	probably benign
R5135:Pakap	UTSW	4	57,855,912 (GRCm39)	missense	probably benign	0.00
R5292:Pakap	UTSW	4	57,855,356 (GRCm39)	missense	probably damaging	0.98
R5420:Pakap	UTSW	4	57,856,434 (GRCm39)	missense	probably damaging	1.00
R5420:Pakap	UTSW	4	57,856,062 (GRCm39)	missense	probably benign	0.08
R5442:Pakap	UTSW	4	57,637,876 (GRCm39)	missense	probably null
R5517:Pakap	UTSW	4	57,855,987 (GRCm39)	missense	probably damaging	0.99
R5648:Pakap	UTSW	4	57,854,848 (GRCm39)	missense	probably damaging	1.00
R5886:Pakap	UTSW	4	57,856,295 (GRCm39)	missense	probably damaging	1.00
R5993:Pakap	UTSW	4	57,855,273 (GRCm39)	missense	possibly damaging	0.86
R6133:Pakap	UTSW	4	57,855,516 (GRCm39)	nonsense	probably null
R6189:Pakap	UTSW	4	57,855,928 (GRCm39)	missense	probably benign	0.00
R6221:Pakap	UTSW	4	57,855,618 (GRCm39)	nonsense	probably null
R6320:Pakap	UTSW	4	57,710,173 (GRCm39)	missense	probably damaging	1.00
R6365:Pakap	UTSW	4	57,709,675 (GRCm39)	nonsense	probably null
R6532:Pakap	UTSW	4	57,855,174 (GRCm39)	missense	probably benign	0.00
R6760:Pakap	UTSW	4	57,856,026 (GRCm39)	missense	probably damaging	1.00
R6792:Pakap	UTSW	4	57,855,880 (GRCm39)	missense	possibly damaging	0.90
R6983:Pakap	UTSW	4	57,709,973 (GRCm39)	missense	probably damaging	1.00
R7090:Pakap	UTSW	4	57,648,042 (GRCm39)	missense	probably benign	0.00
R7128:Pakap	UTSW	4	57,855,816 (GRCm39)	missense	probably benign	0.03
R7269:Pakap	UTSW	4	57,855,217 (GRCm39)	missense	probably damaging	1.00
R7726:Pakap	UTSW	4	57,709,876 (GRCm39)	missense	probably damaging	1.00
R7744:Pakap	UTSW	4	57,709,519 (GRCm39)	missense	probably damaging	0.97
R7837:Pakap	UTSW	4	57,855,262 (GRCm39)	missense	probably damaging	1.00
R7940:Pakap	UTSW	4	57,883,026 (GRCm39)	missense	probably damaging	0.98
R7946:Pakap	UTSW	4	57,710,045 (GRCm39)	missense	probably damaging	1.00
R8094:Pakap	UTSW	4	57,886,319 (GRCm39)	missense	possibly damaging	0.81
R8275:Pakap	UTSW	4	57,886,329 (GRCm39)	critical splice donor site	probably null
R8702:Pakap	UTSW	4	57,709,489 (GRCm39)	nonsense	probably null
R8836:Pakap	UTSW	4	57,709,916 (GRCm39)	missense	probably benign	0.01
R9010:Pakap	UTSW	4	57,883,192 (GRCm39)	missense	probably damaging	1.00
R9016:Pakap	UTSW	4	57,637,857 (GRCm39)	missense	unknown
R9060:Pakap	UTSW	4	57,855,412 (GRCm39)	missense	probably damaging	1.00
R9215:Pakap	UTSW	4	57,709,595 (GRCm39)	missense	probably damaging	0.97
R9652:Pakap	UTSW	4	57,710,125 (GRCm39)	missense	possibly damaging	0.51
X0065:Pakap	UTSW	4	57,709,805 (GRCm39)	missense	probably benign
Z1177:Pakap	UTSW	4	57,856,348 (GRCm39)	missense	probably damaging	1.00

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 1191 of the Akap2 isoform 1 transcript, in exon 1 of 4 total exons. Multiple transcripts of Akap2 exist on Ensembl with the longest isoform containing 5 total exons. The mutated nucleotide causes a glutamine to arginine substitution at amino acid 229 for all of the encoded isoforms. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Akap2 gene produces six different transcripts each encoding a distinct protein isoform collectively known as AKAP-KL proteins. Different isoforms predominate in different tissues. Isoform 1 is 893 amino acids long, and shares the same first 780 amino acids with the other isoforms. All AKAP-KL isoforms contain a 20-residue domain that strongly binds regulatory subunits (RII) of protein kinase AII and is highly homologous with the RII tethering site in neuronal AKAP75 (amino acids 586-605). AKAP-KL can interact with the actin cytoskeleton and is likely important for localizing the regulatory subunits of protein kinase AII. AKAP-KL proteins also contain two coiled coil domains, which may mediate protein interactions, at residues 246-316 and 729-766. The Q229R mutation is predicted to be possibly damaging by the PolyPhen program.

Posted On

2009-11-09