Mutagenetix > Incidental Mutation

Incidental Mutation 'R6226:Pitx2'

504323

Institutional Source

Beutler Lab

Gene Symbol

Pitx2

Ensembl Gene

ENSMUSG00000028023

Gene Name

paired-like homeodomain transcription factor 2

Synonyms

solurshin, Brx1, Pitx2c, Otlx2, Munc30, Ptx2, Pitx2a, Brx1b, Brx1a, Rieg, Pitx2b

MMRRC Submission

044397-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6226 (G1)

Quality Score

164.009

Status

Not validated

Chromosome

Chromosomal Location

128993527-129013240 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 129009491 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Tryptophan at position 130 (R130W)

Ref Sequence

ENSEMBL: ENSMUSP00000133756 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029657] [ENSMUST00000042587] [ENSMUST00000106382] [ENSMUST00000172645] [ENSMUST00000174623] [ENSMUST00000174661]

AlphaFold

P97474

Predicted Effect

probably benign
Transcript: ENSMUST00000029657

Predicted Effect

probably damaging
Transcript: ENSMUST00000042587
AA Change: R137W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000047359
Gene: ENSMUSG00000028023
AA Change: R137W

Domain	Start	End	E-Value	Type
HOX	92	154	6.5e-26	SMART
low complexity region	213	236	N/A	INTRINSIC
low complexity region	244	262	N/A	INTRINSIC
low complexity region	263	280	N/A	INTRINSIC
Pfam:OAR	282	300	4.9e-11	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000106382
AA Change: R84W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000101990
Gene: ENSMUSG00000028023
AA Change: R84W

Domain	Start	End	E-Value	Type
HOX	39	101	6.5e-26	SMART
low complexity region	160	183	N/A	INTRINSIC
low complexity region	191	209	N/A	INTRINSIC
low complexity region	210	227	N/A	INTRINSIC
Pfam:OAR	228	248	2.9e-12	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000172645
AA Change: R117W

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

SMART Domains

Protein: ENSMUSP00000134692
Gene: ENSMUSG00000028023
AA Change: R117W

Domain	Start	End	E-Value	Type
HOX	72	134	6.5e-26	SMART
low complexity region	193	216	N/A	INTRINSIC
low complexity region	224	242	N/A	INTRINSIC
low complexity region	243	260	N/A	INTRINSIC
Pfam:OAR	262	280	9.5e-12	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000174623
AA Change: R137W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000139328
Gene: ENSMUSG00000028023
AA Change: R137W

Domain	Start	End	E-Value	Type
HOX	92	151	1.37e-10	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000174661
AA Change: R130W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000133756
Gene: ENSMUSG00000028023
AA Change: R130W

Domain	Start	End	E-Value	Type
HOX	85	147	6.5e-26	SMART
low complexity region	206	229	N/A	INTRINSIC
low complexity region	237	255	N/A	INTRINSIC
low complexity region	256	273	N/A	INTRINSIC
Pfam:OAR	274	294	1.8e-12	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184283

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000187145

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.3%
20x: 95.3%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted mutations show failed ventral body wall closure, right pulmonary isomerism, septal and valve defects, absent ocular muscles, arrested pituitary and tooth development, optic nerve, mandible and maxilla defects, and embryonic death. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 70 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actn2	T	C	13: 12,293,853 (GRCm39)	T62A	probably benign	Het
Adam33	G	A	2: 130,897,530 (GRCm39)	T265I	probably damaging	Het
Afap1l2	T	C	19: 56,904,560 (GRCm39)	T654A	probably benign	Het
Agrn	A	G	4: 156,258,066 (GRCm39)	S992P	probably damaging	Het
Anapc1	A	G	2: 128,492,292 (GRCm39)	F939L	probably damaging	Het
Anks1	G	A	17: 28,276,304 (GRCm39)	V1016I	probably benign	Het
Ankzf1	A	G	1: 75,173,238 (GRCm39)	T401A	probably benign	Het
Atad1	G	T	19: 32,678,987 (GRCm39)	D105E	probably benign	Het
Carmil2	A	G	8: 106,415,664 (GRCm39)	T313A	possibly damaging	Het
Cdk15	T	C	1: 59,304,792 (GRCm39)	V131A	probably damaging	Het
Cldnd1	A	T	16: 58,551,663 (GRCm39)		probably null	Het
Col16a1	A	T	4: 129,948,882 (GRCm39)		probably benign	Het
Cts3	T	A	13: 61,716,535 (GRCm39)	I34L	probably benign	Het
Dnah7b	A	C	1: 46,165,828 (GRCm39)	K498Q	probably benign	Het
Dnase2b	A	G	3: 146,290,318 (GRCm39)	Y218H	probably benign	Het
Dsg2	T	A	18: 20,712,506 (GRCm39)	V170D	probably damaging	Het
Dst	T	C	1: 34,309,955 (GRCm39)	V1543A	probably damaging	Het
Ell3	A	T	2: 121,272,258 (GRCm39)	I72K	probably damaging	Het
Fank1	A	G	7: 133,463,927 (GRCm39)	Y41C	probably benign	Het
Foxd3	T	C	4: 99,545,261 (GRCm39)	Y134H	probably damaging	Het
Frmd6	A	G	12: 70,910,685 (GRCm39)		probably benign	Het
Gale	A	G	4: 135,692,916 (GRCm39)	E53G	possibly damaging	Het
Glis3	A	G	19: 28,294,702 (GRCm39)	S699P	probably damaging	Het
Gm12830	T	A	4: 114,702,246 (GRCm39)	M136K	unknown	Het
Grik3	T	C	4: 125,553,582 (GRCm39)	V438A	probably benign	Het
Gsap	A	G	5: 21,422,429 (GRCm39)	N133D	probably damaging	Het
Gsg1	T	A	6: 135,217,110 (GRCm39)	D239V	probably damaging	Het
H2-T10	A	T	17: 36,431,975 (GRCm39)	W23R	probably damaging	Het
Itgae	A	G	11: 73,031,583 (GRCm39)	T1100A	probably benign	Het
Kcnh7	A	T	2: 62,607,903 (GRCm39)	F559L	probably damaging	Het
Kdm5b	G	T	1: 134,536,616 (GRCm39)	R612L	probably damaging	Het
Lrrc74a	T	A	12: 86,795,231 (GRCm39)	N253K	possibly damaging	Het
Mcm3ap	A	G	10: 76,351,540 (GRCm39)	H1961R	possibly damaging	Het
Ncam1	C	T	9: 49,476,304 (GRCm39)	E262K	probably benign	Het
Nckap1	A	G	2: 80,339,125 (GRCm39)	S968P	possibly damaging	Het
Nkapd1	T	C	9: 50,519,070 (GRCm39)	T181A	possibly damaging	Het
Nr2f2	T	G	7: 70,009,744 (GRCm39)	S112R	probably benign	Het
Nup93	T	C	8: 95,013,165 (GRCm39)	W137R	probably damaging	Het
Or10ag53	A	G	2: 87,082,736 (GRCm39)	S152G	probably benign	Het
Or2t26	A	G	11: 49,039,660 (GRCm39)	D192G	possibly damaging	Het
Or4a78	A	T	2: 89,497,333 (GRCm39)	L299H	probably damaging	Het
Or52n1	A	T	7: 104,383,243 (GRCm39)	F109L	probably damaging	Het
Or8b12	T	A	9: 37,657,433 (GRCm39)	M1K	probably null	Het
Or8b55	T	C	9: 38,727,666 (GRCm39)	I289T	probably damaging	Het
Otogl	A	T	10: 107,607,067 (GRCm39)	Y2105*	probably null	Het
Pibf1	A	G	14: 99,338,555 (GRCm39)	S24G	probably damaging	Het
Pkd1l1	T	C	11: 8,851,287 (GRCm39)	N715S	probably benign	Het
Pou6f2	A	T	13: 18,303,739 (GRCm39)	I123N	possibly damaging	Het
Prss29	T	A	17: 25,539,513 (GRCm39)	H35Q	possibly damaging	Het
Ptpn21	A	G	12: 98,646,375 (GRCm39)	F1028L	probably benign	Het
Ptpn21	A	T	12: 98,681,431 (GRCm39)	Y68N	probably damaging	Het
Ptprk	A	G	10: 28,440,099 (GRCm39)	T856A	probably benign	Het
Rnd2	C	T	11: 101,359,825 (GRCm39)	L57F	probably damaging	Het
Rpl22l1	A	G	3: 28,860,676 (GRCm39)	T13A	possibly damaging	Het
Rptn	C	G	3: 93,305,437 (GRCm39)	H923Q	possibly damaging	Het
Sec14l5	G	A	16: 4,994,429 (GRCm39)	V408I	probably damaging	Het
Serpina5	T	C	12: 104,068,037 (GRCm39)	S33P	possibly damaging	Het
Sgip1	A	G	4: 102,823,392 (GRCm39)	N524S	probably damaging	Het
Shkbp1	C	A	7: 27,051,405 (GRCm39)	R218M	probably null	Het
Sorcs1	T	A	19: 50,169,852 (GRCm39)	I970F	probably damaging	Het
Spg11	A	G	2: 121,918,743 (GRCm39)	V962A	possibly damaging	Het
Sptbn1	A	G	11: 30,086,054 (GRCm39)	M1205T	probably damaging	Het
Sufu	G	A	19: 46,462,093 (GRCm39)	V369M	probably damaging	Het
Tmem98	T	C	11: 80,712,220 (GRCm39)	F219S	probably benign	Het
Trim27	T	C	13: 21,365,086 (GRCm39)		probably benign	Het
Trim43b	T	C	9: 88,973,328 (GRCm39)	E135G	possibly damaging	Het
Ube2m	A	G	7: 12,769,815 (GRCm39)	V110A	probably damaging	Het
Ugt2b36	A	G	5: 87,239,989 (GRCm39)	V132A	probably damaging	Het
Usp36	A	T	11: 118,168,100 (GRCm39)	S86T	probably damaging	Het
Zfp941	A	T	7: 140,392,398 (GRCm39)	D320E	probably benign	Het

Other mutations in Pitx2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01409:Pitx2	APN	3	129,008,413 (GRCm39)	missense	probably damaging	0.99
IGL02110:Pitx2	APN	3	129,012,466 (GRCm39)	missense	probably damaging	0.99
Chihuahua	UTSW	3	129,009,489 (GRCm39)	missense	probably damaging	1.00
milly	UTSW	3	129,012,223 (GRCm39)	missense	probably damaging	1.00
R0014:Pitx2	UTSW	3	129,012,148 (GRCm39)	missense	possibly damaging	0.70
R1083:Pitx2	UTSW	3	129,012,418 (GRCm39)	missense	probably damaging	1.00
R1474:Pitx2	UTSW	3	129,012,488 (GRCm39)	missense	probably damaging	1.00
R1789:Pitx2	UTSW	3	129,012,403 (GRCm39)	missense	probably damaging	1.00
R1945:Pitx2	UTSW	3	129,012,185 (GRCm39)	missense	probably damaging	1.00
R5305:Pitx2	UTSW	3	129,009,489 (GRCm39)	missense	probably damaging	1.00
R5950:Pitx2	UTSW	3	129,012,169 (GRCm39)	missense	probably damaging	1.00
R6114:Pitx2	UTSW	3	128,998,062 (GRCm39)	splice site	probably null
R6189:Pitx2	UTSW	3	129,012,118 (GRCm39)	missense	probably damaging	1.00
R6192:Pitx2	UTSW	3	129,009,521 (GRCm39)	missense	probably benign	0.09
R6526:Pitx2	UTSW	3	129,008,432 (GRCm39)	critical splice donor site	probably null
R6778:Pitx2	UTSW	3	129,012,392 (GRCm39)	missense	probably damaging	1.00
R6885:Pitx2	UTSW	3	129,012,257 (GRCm39)	missense	probably damaging	1.00
R7575:Pitx2	UTSW	3	129,009,375 (GRCm39)	missense	probably damaging	1.00
R8390:Pitx2	UTSW	3	129,012,507 (GRCm39)	missense	probably damaging	0.96
R8766:Pitx2	UTSW	3	129,012,223 (GRCm39)	missense	probably damaging	1.00
R9021:Pitx2	UTSW	3	129,008,432 (GRCm39)	critical splice donor site	probably null
R9236:Pitx2	UTSW	3	129,009,345 (GRCm39)	missense	probably damaging	1.00
R9744:Pitx2	UTSW	3	129,009,467 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GGGAGTCTGACCCGAAACTATG -3'
(R):5'- CACAATGCCCTTTGCTGAGG -3'

Sequencing Primer
(F):5'- TGCTTTTTCAGAGAAAGATAAGGGCC -3'
(R):5'- AATGCCCTTTGCTGAGGAATGC -3'

Posted On

2018-02-28