Incidental Mutation 'R7575:Pitx2'
ID 586311
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 045632-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7575 (G1)
Quality Score 225.009
Status Not validated
Chromosome 3
Chromosomal Location 128993527-129013240 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 129009375 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Leucine at position 98 (H98L)
Ref Sequence ENSEMBL: ENSMUSP00000047359 (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: H98L

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000047359
Gene: ENSMUSG00000028023
AA Change: H98L

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000106382
AA Change: H45L

PolyPhen 2 Score 0.875 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000101990
Gene: ENSMUSG00000028023
AA Change: H45L

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000172645
AA Change: H78L

PolyPhen 2 Score 0.863 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000134692
Gene: ENSMUSG00000028023
AA Change: H78L

DomainStartEndE-ValueType
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: H98L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000139328
Gene: ENSMUSG00000028023
AA Change: H98L

DomainStartEndE-ValueType
HOX 92 151 1.37e-10 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000174661
AA Change: H91L

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000133756
Gene: ENSMUSG00000028023
AA Change: H91L

DomainStartEndE-ValueType
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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.0%
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: 91 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
3425401B19Rik C T 14: 32,384,589 (GRCm39) V459I probably benign Het
4921539E11Rik T C 4: 103,088,192 (GRCm39) D439G probably damaging Het
Adam18 T C 8: 25,115,873 (GRCm39) N607S possibly damaging Het
Adamtsl3 A T 7: 82,223,756 (GRCm39) N1179I possibly damaging Het
Adarb1 A G 10: 77,139,129 (GRCm39) F552S probably damaging Het
Ago1 T C 4: 126,347,701 (GRCm39) E394G probably benign Het
Alb G A 5: 90,613,788 (GRCm39) C224Y probably damaging Het
Alms1 T A 6: 85,599,141 (GRCm39) H1322Q possibly damaging Het
Arhgef18 T G 8: 3,501,635 (GRCm39) V643G probably damaging Het
Asah2 T C 19: 31,994,103 (GRCm39) Q414R probably benign Het
Atpsckmt C T 15: 31,606,186 (GRCm39) A48V probably damaging Het
Bbc3 G A 7: 16,046,292 (GRCm39) R76H possibly damaging Het
Bub1b T A 2: 118,471,639 (GRCm39) S1000T possibly damaging Het
Bud23 A T 5: 135,089,982 (GRCm39) Y70* probably null Het
C1d A G 11: 17,212,694 (GRCm39) E13G probably damaging Het
Camk1 T A 6: 113,315,325 (GRCm39) I158F probably damaging Het
Ccr2 A C 9: 123,905,843 (GRCm39) D41A probably benign Het
Cdh18 G T 15: 23,400,683 (GRCm39) E348* probably null Het
Col6a3 A G 1: 90,738,321 (GRCm39) L1066P possibly damaging Het
Cyp11b1 T A 15: 74,711,162 (GRCm39) D172V probably benign Het
Cyp2j8 A G 4: 96,358,785 (GRCm39) I378T possibly damaging Het
Cys1 T A 12: 24,718,647 (GRCm39) K69* probably null Het
Dip2c A G 13: 9,678,048 (GRCm39) K1165E probably damaging Het
Drd3 A T 16: 43,637,496 (GRCm39) I232F probably benign Het
Dusp7 T C 9: 106,250,876 (GRCm39) C334R probably damaging Het
Eppk1 A G 15: 75,995,442 (GRCm39) S480P not run Het
Erc1 G T 6: 119,801,721 (GRCm39) P99T possibly damaging Het
Fam170b C T 14: 32,558,155 (GRCm39) P330L unknown Het
Fasn G T 11: 120,703,513 (GRCm39) T1573K possibly damaging Het
Fras1 A T 5: 96,691,173 (GRCm39) T130S probably benign Het
Fzd4 A G 7: 89,056,918 (GRCm39) I322V possibly damaging Het
Gbp10 G A 5: 105,384,015 (GRCm39) probably benign Het
Gdpd4 A T 7: 97,647,448 (GRCm39) H365L probably benign Het
Gfy A G 7: 44,827,524 (GRCm39) S191P probably benign Het
Ghr A T 15: 3,349,994 (GRCm39) S395T probably damaging Het
Git2 C T 5: 114,904,550 (GRCm39) R123H probably damaging Het
Htt A G 5: 35,062,987 (GRCm39) D2873G probably damaging Het
Idua A T 5: 108,829,565 (GRCm39) D476V probably damaging Het
Inppl1 G A 7: 101,477,689 (GRCm39) R683W probably damaging Het
Ipp T C 4: 116,389,841 (GRCm39) S466P probably benign Het
Iqgap2 A G 13: 95,798,131 (GRCm39) V1058A probably damaging Het
Jmy A T 13: 93,601,103 (GRCm39) Y434* probably null Het
Kmt2d CTGCTGCTG CTGCTGCTGATGCTGCTG 15: 98,747,492 (GRCm39) probably benign Het
Mogs T G 6: 83,092,816 (GRCm39) S85R probably damaging Het
Mroh2b A T 15: 4,964,087 (GRCm39) D863V probably damaging Het
Mtmr10 A T 7: 63,947,213 (GRCm39) I43F probably damaging Het
Mtr T C 13: 12,213,963 (GRCm39) D903G probably benign Het
Ncor1 A G 11: 62,274,082 (GRCm39) V186A probably benign Het
Notch3 C T 17: 32,373,793 (GRCm39) D472N possibly damaging Het
Or4k44 A T 2: 111,368,597 (GRCm39) F12L probably damaging Het
Or6c68 T C 10: 129,157,728 (GRCm39) F79L probably damaging Het
Or8j3c A G 2: 86,253,582 (GRCm39) F146S probably benign Het
Or9i1 T C 19: 13,839,381 (GRCm39) S75P probably damaging Het
Oxr1 T G 15: 41,686,758 (GRCm39) L547V possibly damaging Het
Pappa2 A T 1: 158,642,100 (GRCm39) C1319S probably damaging Het
Papss1 A C 3: 131,348,857 (GRCm39) K623N probably damaging Het
Parp4 T C 14: 56,875,375 (GRCm39) F1198S probably benign Het
Pcare T A 17: 72,057,850 (GRCm39) Q609L probably damaging Het
Pcnt A T 10: 76,225,086 (GRCm39) V1806D probably benign Het
Polq C A 16: 36,911,496 (GRCm39) D2410E probably benign Het
Prdm9 C T 17: 15,764,890 (GRCm39) C630Y probably damaging Het
Preb A T 5: 31,115,839 (GRCm39) D201E probably damaging Het
Rasa3 A T 8: 13,645,887 (GRCm39) I151N possibly damaging Het
Rasgrp2 T A 19: 6,454,397 (GRCm39) S147T probably damaging Het
Rev3l A G 10: 39,697,441 (GRCm39) D646G possibly damaging Het
Sdc1 A G 12: 8,840,619 (GRCm39) E128G probably damaging Het
Slamf7 A C 1: 171,466,762 (GRCm39) C148G probably damaging Het
Slc19a2 T C 1: 164,084,691 (GRCm39) S194P probably damaging Het
Spata31 C T 13: 65,070,726 (GRCm39) P958L unknown Het
Sprr2b CTGAGCCTTGTCCTCCTCCAAAGTGCCCTGAGCCTTGTCCTCCCCCAGTATGCTGTGAGCCTTGTCCTCCTCCAAAGTGCCCTGAGCCTTGTCCTCCCCCAGTATGCTGTGAGCCTTGTCCTCC CTGAGCCTTGTCCTCCTCCAAAGTGCCCTGAGCCTTGTCCTCCCCCAGTATGCTGTGAGCCTTGTCCTCC 3: 92,224,826 (GRCm39) probably benign Het
Stradb A G 1: 59,027,739 (GRCm39) I90V probably benign Het
Tas2r134 A G 2: 51,518,166 (GRCm39) D215G probably damaging Het
Tbc1d4 T C 14: 101,685,025 (GRCm39) K1209E probably damaging Het
Thbs1 A G 2: 117,953,409 (GRCm39) D942G probably damaging Het
Tmem107 C T 11: 68,963,633 (GRCm39) P139S probably benign Het
Tmem216 A T 19: 10,529,266 (GRCm39) M40K probably benign Het
Tpte A G 8: 22,845,498 (GRCm39) Y516C probably damaging Het
Trim54 G A 5: 31,291,431 (GRCm39) G184D possibly damaging Het
Try5 A T 6: 41,288,748 (GRCm39) L157Q probably benign Het
Ubqlnl G A 7: 103,797,697 (GRCm39) A600V probably damaging Het
Uhrf2 C A 19: 30,048,768 (GRCm39) P258Q probably damaging Het
Ush2a A T 1: 188,554,885 (GRCm39) E3554D possibly damaging Het
Usp40 A C 1: 87,877,682 (GRCm39) L1158W probably damaging Het
Vmn1r121 T A 7: 20,832,198 (GRCm39) R81* probably null Het
Vmn1r203 C A 13: 22,708,588 (GRCm39) T123K probably benign Het
Vmn2r101 T C 17: 19,831,654 (GRCm39) V550A probably benign Het
Wdr49 A T 3: 75,358,193 (GRCm39) M184K probably damaging Het
Wipi2 A G 5: 142,643,987 (GRCm39) N123S probably damaging Het
Zbtb14 T C 17: 69,694,442 (GRCm39) F47L probably damaging Het
Zc3h7b C A 15: 81,662,086 (GRCm39) S385* probably null Het
Zhx2 T A 15: 57,686,658 (GRCm39) F676I probably damaging Het
Other mutations in Pitx2
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- AATAAAACGTGCGGCGCTG -3'
(R):5'- CAGGCTCTGATTCTTGGCAAGG -3'

Sequencing Primer
(F):5'- TGCCGAGCACAGACCTTTC -3'
(R):5'- TTCTTCGCGAGTGGACAT -3'
Posted On 2019-10-24