Mutagenetix > Incidental Mutation

Incidental Mutation 'R6189:Pitx2'

502364

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

044329-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6189 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

128993527-129013240 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 129012118 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 130 (Y130H)

Ref Sequence

ENSEMBL: ENSMUSP00000101990 (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: Y183H

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

SMART Domains

Protein: ENSMUSP00000047359
Gene: ENSMUSG00000028023
AA Change: Y183H

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: Y130H

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

SMART Domains

Protein: ENSMUSP00000101990
Gene: ENSMUSG00000028023
AA Change: Y130H

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: Y163H

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

SMART Domains

Protein: ENSMUSP00000134692
Gene: ENSMUSG00000028023
AA Change: Y163H

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 benign
Transcript: ENSMUST00000174623

SMART Domains

Protein: ENSMUSP00000139328
Gene: ENSMUSG00000028023

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000174661
AA Change: Y176H

PolyPhen 2 Score 0.693 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000133756
Gene: ENSMUSG00000028023
AA Change: Y176H

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: ENSMUST00000187145

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000199637

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.5%

Validation Efficiency

97% (74/76)

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A530064D06Rik	A	G	17: 48,474,222 (GRCm39)		probably benign	Het
Abca8a	T	C	11: 109,921,710 (GRCm39)	D1448G	probably damaging	Het
Actn2	C	T	13: 12,291,326 (GRCm39)	D693N	probably damaging	Het
Adam3	A	C	8: 25,201,352 (GRCm39)	I267R	probably benign	Het
Aldh1l2	A	G	10: 83,343,877 (GRCm39)		probably null	Het
C4bp	T	C	1: 130,564,556 (GRCm39)	Y376C	probably damaging	Het
Cacna1h	A	G	17: 25,616,818 (GRCm39)	W101R	probably damaging	Het
Ccdc97	T	A	7: 25,415,523 (GRCm39)	T47S	probably benign	Het
Cenatac	G	A	9: 44,321,618 (GRCm39)	R328C	probably benign	Het
Cnot6l	G	A	5: 96,246,136 (GRCm39)	T171I	probably benign	Het
Cntnap2	T	A	6: 47,248,232 (GRCm39)	S1213T	probably damaging	Het
Cxcl10	A	T	5: 92,495,972 (GRCm39)	L55Q	probably benign	Het
Cyp1a1	T	C	9: 57,607,966 (GRCm39)	V198A	probably damaging	Het
Dclre1b	A	G	3: 103,710,849 (GRCm39)	V354A	probably damaging	Het
Dmxl1	C	T	18: 50,026,402 (GRCm39)	H1837Y	probably benign	Het
Dnajc13	G	C	9: 104,091,085 (GRCm39)	D665E	probably benign	Het
Dnmbp	T	C	19: 43,878,748 (GRCm39)	T108A	probably benign	Het
Dnmbp	T	A	19: 43,889,950 (GRCm39)	T606S	probably benign	Het
Dok5	T	A	2: 170,642,771 (GRCm39)	I23N	probably damaging	Het
Eml2	G	A	7: 18,935,088 (GRCm39)	V432I	probably damaging	Het
Epha5	A	T	5: 84,385,399 (GRCm39)	F311I	probably damaging	Het
Erbb4	T	A	1: 68,083,075 (GRCm39)	M1059L	probably benign	Het
Fbxo40	A	G	16: 36,786,526 (GRCm39)	I681T	probably benign	Het
Flg2	T	A	3: 93,127,381 (GRCm39)	C2098S	unknown	Het
Gpr87	T	A	3: 59,086,650 (GRCm39)	D285V	probably damaging	Het
Hrh1	T	A	6: 114,456,959 (GRCm39)	V80D	probably damaging	Het
Hunk	G	A	16: 90,284,769 (GRCm39)	R351K	probably benign	Het
Ifna12	A	G	4: 88,521,248 (GRCm39)	W100R	probably damaging	Het
Ift57	G	A	16: 49,584,176 (GRCm39)	G310S	probably damaging	Het
Igf1r	T	A	7: 67,857,084 (GRCm39)	Y1015*	probably null	Het
Igkv14-130	T	C	6: 67,768,432 (GRCm39)	I96T	probably damaging	Het
Il34	C	T	8: 111,469,350 (GRCm39)	S155N	probably benign	Het
Itga7	T	C	10: 128,786,272 (GRCm39)	S938P	possibly damaging	Het
Itgam	A	G	7: 127,711,676 (GRCm39)	M764V	probably benign	Het
Lao1	T	A	4: 118,825,077 (GRCm39)	M299K	probably benign	Het
Lnpep	A	T	17: 17,787,001 (GRCm39)	S533T	possibly damaging	Het
Lrp4	T	C	2: 91,305,579 (GRCm39)	V283A	possibly damaging	Het
Magi3	G	T	3: 103,958,181 (GRCm39)	H635N	probably damaging	Het
Mecr	A	T	4: 131,592,565 (GRCm39)		probably null	Het
Mgrn1	T	C	16: 4,728,674 (GRCm39)		probably null	Het
Mical2	A	C	7: 112,012,087 (GRCm39)	N646H	probably damaging	Het
Mymk	C	T	2: 26,957,377 (GRCm39)	V39I	possibly damaging	Het
Nav3	T	C	10: 109,555,880 (GRCm39)	S1684G	probably damaging	Het
Ntn5	A	T	7: 45,342,644 (GRCm39)	D330V	probably benign	Het
Nup42	G	T	5: 24,380,452 (GRCm39)	G149V	probably damaging	Het
Nutm2	T	A	13: 50,623,774 (GRCm39)	V157D	possibly damaging	Het
Obscn	T	C	11: 58,960,760 (GRCm39)	I3460V	probably benign	Het
Or8u10	A	T	2: 85,915,257 (GRCm39)	M288K	possibly damaging	Het
Pakap	A	G	4: 57,855,928 (GRCm39)	E419G	probably benign	Het
Pcdh15	C	T	10: 74,178,483 (GRCm39)	A580V	probably null	Het
Pcdhb10	T	A	18: 37,545,456 (GRCm39)	H177Q	probably damaging	Het
Pmch	G	T	10: 87,927,248 (GRCm39)		probably null	Het
Pofut2	T	A	10: 77,104,420 (GRCm39)	I399N	probably damaging	Het
Prr36	C	A	8: 4,264,177 (GRCm39)		probably benign	Het
Ptprq	C	A	10: 107,353,748 (GRCm39)	C2256F	probably damaging	Het
Rassf5	G	A	1: 131,172,716 (GRCm39)	A51V	probably damaging	Het
Retnla	A	G	16: 48,663,258 (GRCm39)	I54V	probably benign	Het
Rimbp2	A	G	5: 128,880,961 (GRCm39)	L142P	probably benign	Het
Ripk1	A	G	13: 34,216,484 (GRCm39)	T564A	probably benign	Het
Robo4	G	A	9: 37,314,829 (GRCm39)	E228K	probably benign	Het
Rsf1	GGCG	GGCGACGGCTGCG	7: 97,229,113 (GRCm39)		probably benign	Homo
Rusc1	A	T	3: 88,996,319 (GRCm39)	L132Q	probably damaging	Het
Serpinb9h	A	T	13: 33,588,427 (GRCm39)	E337D	probably benign	Het
Setd1a	T	C	7: 127,377,455 (GRCm39)		probably null	Het
Slc38a6	A	T	12: 73,356,970 (GRCm39)	K122M	probably damaging	Het
Speer4a2	A	G	5: 26,290,691 (GRCm39)	I160T	probably benign	Het
Susd5	A	T	9: 113,924,726 (GRCm39)	D203V	probably damaging	Het
Trip4	G	A	9: 65,786,434 (GRCm39)	R110*	probably null	Het
Tuba4a	T	A	1: 75,193,518 (GRCm39)	I95F	probably benign	Het
Ube2q2	T	A	9: 55,070,267 (GRCm39)	S70T	probably benign	Het
Umodl1	A	G	17: 31,215,256 (GRCm39)	I1027V	possibly damaging	Het
Unc80	G	A	1: 66,716,630 (GRCm39)	V2917I	probably benign	Het
Vmn1r70	T	A	7: 10,367,598 (GRCm39)	C29S	probably benign	Het
Vmn2r94	A	T	17: 18,477,996 (GRCm39)	D138E	probably benign	Het
Wee2	C	T	6: 40,426,617 (GRCm39)	H129Y	probably damaging	Het
Zfp318	TGAAGAAGAAGAAGAAGAAGAAGAAGAAG	TGAAGAAGAAGAAGAAGAAGAAG	17: 46,723,440 (GRCm39)		probably benign	Het
Zfp872	A	T	9: 22,108,427 (GRCm39)	D42V	probably benign	Het
Zic5	T	G	14: 122,702,386 (GRCm39)	D115A	unknown	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
R6192:Pitx2	UTSW	3	129,009,521 (GRCm39)	missense	probably benign	0.09
R6226:Pitx2	UTSW	3	129,009,491 (GRCm39)	missense	probably damaging	1.00
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'- AAACTCATTGTCCCTGTGCC -3'
(R):5'- GGCTGCTCAGGTTGTTCAAG -3'

Sequencing Primer
(F):5'- ATTGTCCCTGTGCCCTCTG -3'
(R):5'- CTCAGGTTGTTCAAGTTATTCAGGC -3'

Posted On

2018-02-27