Mutagenetix > Incidental Mutation

Incidental Mutation 'R0591:Appl2'

55988

Institutional Source

Beutler Lab

Gene Symbol

Appl2

Ensembl Gene

ENSMUSG00000020263

Gene Name

adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2

Synonyms

Dip3b

MMRRC Submission

038781-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0591 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

83435897-83484602 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 83460509 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Lysine at position 116 (I116K)

Ref Sequence

ENSEMBL: ENSMUSP00000020500 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020500] [ENSMUST00000146876] [ENSMUST00000150685] [ENSMUST00000176294]

AlphaFold

Q8K3G9

Predicted Effect

possibly damaging
Transcript: ENSMUST00000020500
AA Change: I116K

PolyPhen 2 Score 0.936 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000020500
Gene: ENSMUSG00000020263
AA Change: I116K

Domain	Start	End	E-Value	Type
Pfam:BAR_3	7	248	6.4e-69	PFAM
PH	278	377	1.2e-7	SMART
Pfam:PTB	491	613	6e-7	PFAM
Pfam:PID	492	611	1.6e-8	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133719

Predicted Effect

possibly damaging
Transcript: ENSMUST00000146876
AA Change: I116K

PolyPhen 2 Score 0.881 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000121336
Gene: ENSMUSG00000020263
AA Change: I116K

Domain	Start	End	E-Value	Type
PDB:4H8S\|D	2	209	1e-141	PDB

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147118

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147582

Predicted Effect

probably benign
Transcript: ENSMUST00000150685

SMART Domains

Protein: ENSMUSP00000115903
Gene: ENSMUSG00000020263

Domain	Start	End	E-Value	Type
PDB:4H8S\|D	2	95	4e-59	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000176294

SMART Domains

Protein: ENSMUSP00000135645
Gene: ENSMUSG00000020263

Domain	Start	End	E-Value	Type
PDB:4H8S\|D	2	95	1e-53	PDB

Meta Mutation Damage Score

0.2118

Coding Region Coverage

1x: 99.7%
3x: 99.2%
10x: 97.7%
20x: 95.3%

Validation Efficiency

100% (62/62)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is one of two effectors of the small GTPase RAB5A/Rab5, which are involved in a signal transduction pathway. Both effectors contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain, and they bind the Rab5 through the BAR domain. They are associated with endosomal membranes and can be translocated to the nucleus in response to the EGF stimulus. They interact with the NuRD/MeCP1 complex (nucleosome remodeling and deacetylase /methyl-CpG-binding protein 1 complex) and are required for efficient cell proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3) involving this gene and the PSAP2 gene results in 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome. [provided by RefSeq, Oct 2011]
PHENOTYPE: Mice homozygous for a null allele display altered red blood cell physiology. Mutant MEFs exhibit defects in HGF-induced Akt activation, migration, and invasion. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	G	T	3: 137,774,704 (GRCm39)	E1298*	probably null	Het
Aadacl2fm2	C	A	3: 59,659,550 (GRCm39)	Y334*	probably null	Het
Adam19	T	C	11: 46,012,238 (GRCm39)		probably benign	Het
Agt	A	T	8: 125,283,678 (GRCm39)	S480R	possibly damaging	Het
Anapc1	G	T	2: 128,461,252 (GRCm39)	D1769E	probably benign	Het
Aox4	T	C	1: 58,278,261 (GRCm39)		probably benign	Het
Apol9b	G	A	15: 77,619,830 (GRCm39)	V209I	possibly damaging	Het
BC051665	A	G	13: 60,932,422 (GRCm39)		probably benign	Het
Cactin	G	T	10: 81,159,837 (GRCm39)	E89*	probably null	Het
Carf	G	T	1: 60,165,073 (GRCm39)		probably benign	Het
Ccdc167	A	G	17: 29,924,235 (GRCm39)		probably benign	Het
Ceacam3	G	A	7: 16,885,808 (GRCm39)		probably null	Het
Clca4b	T	A	3: 144,621,353 (GRCm39)	K574*	probably null	Het
Crabp1	T	A	9: 54,672,887 (GRCm39)	I64N	probably damaging	Het
Dgkd	T	A	1: 87,842,826 (GRCm39)	I118N	probably damaging	Het
Dglucy	T	C	12: 100,825,777 (GRCm39)		probably benign	Het
Dock10	C	T	1: 80,518,936 (GRCm39)		probably benign	Het
Ednrb	A	T	14: 104,060,710 (GRCm39)		probably null	Het
Ercc6	T	C	14: 32,279,973 (GRCm39)		probably benign	Het
Golga3	A	C	5: 110,336,609 (GRCm39)	Q416P	probably damaging	Het
Gpr12	A	G	5: 146,520,445 (GRCm39)	V159A	probably benign	Het
Heatr5a	A	T	12: 51,956,884 (GRCm39)		probably benign	Het
Helz2	A	G	2: 180,873,909 (GRCm39)	I2195T	probably damaging	Het
Hikeshi	A	T	7: 89,569,295 (GRCm39)	N76K	possibly damaging	Het
Hsd11b1	T	C	1: 192,911,984 (GRCm39)		probably benign	Het
Iftap	A	T	2: 101,406,462 (GRCm39)	D155E	probably benign	Het
Inhba	A	T	13: 16,201,405 (GRCm39)	K322N	probably damaging	Het
Katnal1	A	T	5: 148,829,326 (GRCm39)	F291L	probably damaging	Het
Kcnj9	T	C	1: 172,150,665 (GRCm39)	E316G	probably damaging	Het
Lrsam1	A	G	2: 32,823,935 (GRCm39)		probably benign	Het
Mcf2l	T	G	8: 13,068,751 (GRCm39)	S1075A	probably benign	Het
Mios	T	C	6: 8,215,470 (GRCm39)	V222A	possibly damaging	Het
Mycbp2	A	T	14: 103,433,827 (GRCm39)		probably benign	Het
Nars1	A	T	18: 64,633,638 (GRCm39)	I544N	probably damaging	Het
Or5ak23	A	G	2: 85,245,034 (GRCm39)	L63P	possibly damaging	Het
Pbrm1	A	G	14: 30,768,387 (GRCm39)		probably benign	Het
Plcb4	A	G	2: 135,796,932 (GRCm39)		probably benign	Het
Pnliprp1	A	G	19: 58,723,138 (GRCm39)	D213G	probably damaging	Het
Psap	A	G	10: 60,136,634 (GRCm39)	N538D	possibly damaging	Het
Ptdss1	A	G	13: 67,120,714 (GRCm39)		probably benign	Het
Rap1b	G	A	10: 117,654,522 (GRCm39)		probably benign	Het
Rhcg	T	A	7: 79,244,520 (GRCm39)		probably benign	Het
Ryr1	G	A	7: 28,804,220 (GRCm39)	T550I	possibly damaging	Het
Samm50	G	A	15: 84,095,369 (GRCm39)	G452R	probably benign	Het
Scin	A	G	12: 40,130,929 (GRCm39)		probably null	Het
Sesn3	T	C	9: 14,219,854 (GRCm39)	L81S	probably damaging	Het
Skint6	A	C	4: 112,715,366 (GRCm39)		probably benign	Het
Slc30a4	A	T	2: 122,527,160 (GRCm39)	L411H	probably damaging	Het
Slc44a5	C	T	3: 153,939,782 (GRCm39)		probably benign	Het
Slc4a3	C	T	1: 75,525,665 (GRCm39)	A255V	probably damaging	Het
Slc9b1	A	G	3: 135,088,593 (GRCm39)	N318S	possibly damaging	Het
Tcp11l2	A	T	10: 84,440,458 (GRCm39)	H287L	probably benign	Het
Tex10	C	T	4: 48,456,800 (GRCm39)	R637Q	probably benign	Het
Tnks2	T	A	19: 36,849,962 (GRCm39)	Y605N	probably damaging	Het
Topbp1	T	A	9: 103,227,037 (GRCm39)	N1490K	probably benign	Het
Ube4b	T	G	4: 149,442,034 (GRCm39)		probably benign	Het
Usp4	G	A	9: 108,225,228 (GRCm39)		probably benign	Het
Vezf1	A	T	11: 88,068,435 (GRCm38)		probably benign	Het
Vmn1r184	A	T	7: 25,966,500 (GRCm39)	D82V	probably damaging	Het

Other mutations in Appl2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01681:Appl2	APN	10	83,450,165 (GRCm39)	missense	possibly damaging	0.95
IGL01794:Appl2	APN	10	83,450,158 (GRCm39)	missense	probably benign
IGL01887:Appl2	APN	10	83,457,386 (GRCm39)	unclassified	probably benign
IGL03071:Appl2	APN	10	83,476,970 (GRCm39)	critical splice acceptor site	probably null
IGL03077:Appl2	APN	10	83,457,623 (GRCm39)	unclassified	probably benign
R0006:Appl2	UTSW	10	83,438,762 (GRCm39)	missense	probably damaging	1.00
R0006:Appl2	UTSW	10	83,438,762 (GRCm39)	missense	probably damaging	1.00
R1695:Appl2	UTSW	10	83,457,446 (GRCm39)	missense	probably damaging	0.99
R2217:Appl2	UTSW	10	83,444,601 (GRCm39)	missense	possibly damaging	0.47
R2218:Appl2	UTSW	10	83,444,601 (GRCm39)	missense	possibly damaging	0.47
R4782:Appl2	UTSW	10	83,436,855 (GRCm39)	missense	probably damaging	1.00
R4889:Appl2	UTSW	10	83,476,922 (GRCm39)	missense	probably damaging	1.00
R5109:Appl2	UTSW	10	83,436,871 (GRCm39)	missense	probably benign	0.06
R5460:Appl2	UTSW	10	83,438,696 (GRCm39)	missense	probably benign	0.00
R5512:Appl2	UTSW	10	83,441,682 (GRCm39)	missense	probably damaging	1.00
R6023:Appl2	UTSW	10	83,484,393 (GRCm39)	missense	probably null	0.00
R6047:Appl2	UTSW	10	83,448,765 (GRCm39)	critical splice acceptor site	probably null
R7403:Appl2	UTSW	10	83,450,059 (GRCm39)	missense	probably benign	0.00
R7537:Appl2	UTSW	10	83,453,292 (GRCm39)	missense	possibly damaging	0.69
R8488:Appl2	UTSW	10	83,446,866 (GRCm39)	missense	probably benign	0.02
R9203:Appl2	UTSW	10	83,476,879 (GRCm39)	nonsense	probably null
X0027:Appl2	UTSW	10	83,457,418 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CACTAAGCATGGGCTTCACAGGAC -3'
(R):5'- AGCCTCACTGATACTACAGTCGGG -3'

Sequencing Primer
(F):5'- CCTCTGTTGAACCAGGAACG -3'
(R):5'- CGTGTGTTGAGGACATCCAG -3'

Posted On

2013-07-11