Incidental Mutation 'R2209:Nkx2-1'
ID 239272
Institutional Source Beutler Lab
Gene Symbol Nkx2-1
Ensembl Gene ENSMUSG00000001496
Gene Name NK2 homeobox 1
Synonyms Titf1, thyroid transcription factor-1, thyroid-specific enhancer-binding protein, tinman, T/EBP, Ttf-1
MMRRC Submission 040211-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2209 (G1)
Quality Score 225
Status Not validated
Chromosome 12
Chromosomal Location 56578741-56583570 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 56580293 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Leucine at position 216 (M216L)
Ref Sequence ENSEMBL: ENSMUSP00000136103 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001536] [ENSMUST00000178477]
AlphaFold P50220
Predicted Effect probably benign
Transcript: ENSMUST00000001536
AA Change: M216L

PolyPhen 2 Score 0.147 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000001536
Gene: ENSMUSG00000001496
AA Change: M216L

DomainStartEndE-ValueType
low complexity region 39 69 N/A INTRINSIC
low complexity region 133 147 N/A INTRINSIC
HOX 161 223 9.05e-25 SMART
low complexity region 224 254 N/A INTRINSIC
low complexity region 273 323 N/A INTRINSIC
low complexity region 346 356 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000178477
AA Change: M216L

PolyPhen 2 Score 0.147 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000136103
Gene: ENSMUSG00000001496
AA Change: M216L

DomainStartEndE-ValueType
low complexity region 39 69 N/A INTRINSIC
low complexity region 133 147 N/A INTRINSIC
HOX 161 223 9.05e-25 SMART
low complexity region 224 254 N/A INTRINSIC
low complexity region 273 323 N/A INTRINSIC
low complexity region 346 356 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000182105
Predicted Effect noncoding transcript
Transcript: ENSMUST00000182733
Predicted Effect noncoding transcript
Transcript: ENSMUST00000183231
Predicted Effect noncoding transcript
Transcript: ENSMUST00000218376
Predicted Effect noncoding transcript
Transcript: ENSMUST00000220379
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 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 protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygotes for a targeted mutation have profoundly abnormal lungs and ventral forebrain defects, lack thyroids, pituitary gland, and tracheoesophageal septation, and die at birth from respiratory failure. Carriers show incoordination and high TSH. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 58 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
6430548M08Rik A G 8: 120,884,227 (GRCm39) E330G possibly damaging Het
Apob A C 12: 8,057,752 (GRCm39) D2078A probably benign Het
Arhgap21 T A 2: 20,854,331 (GRCm39) Q1681L probably damaging Het
Arsb A G 13: 93,998,609 (GRCm39) T306A probably benign Het
Brpf3 G A 17: 29,047,394 (GRCm39) D1053N probably damaging Het
Cenpf A T 1: 189,384,795 (GRCm39) I2495N probably benign Het
Col12a1 T C 9: 79,599,634 (GRCm39) K840E possibly damaging Het
Cry1 A G 10: 84,982,619 (GRCm39) L269P probably damaging Het
Cyp21a1 C A 17: 35,021,701 (GRCm39) E289* probably null Het
Dcp2 A T 18: 44,538,581 (GRCm39) K215* probably null Het
Dnaaf11 A G 15: 66,321,400 (GRCm39) I247T probably benign Het
Ecm2 A G 13: 49,683,632 (GRCm39) N537D probably damaging Het
Emid1 G A 11: 5,085,407 (GRCm39) T113M probably benign Het
Exoc8 C T 8: 125,622,918 (GRCm39) W483* probably null Het
Fes A T 7: 80,030,031 (GRCm39) N582K probably damaging Het
Flnb G T 14: 7,905,507 (GRCm38) E1086* probably null Het
Flnc T A 6: 29,455,844 (GRCm39) D2058E possibly damaging Het
Gatb G A 3: 85,561,112 (GRCm39) D543N probably benign Het
Gm14412 A G 2: 177,009,229 (GRCm39) V9A probably damaging Het
Gm4884 T C 7: 40,692,745 (GRCm39) V238A possibly damaging Het
Igfbp5 A G 1: 72,913,096 (GRCm39) V68A possibly damaging Het
Igflr1 T A 7: 30,267,222 (GRCm39) I330N probably damaging Het
Il1r2 A G 1: 40,154,298 (GRCm39) T222A probably benign Het
Krt87 T C 15: 101,330,989 (GRCm39) E419G probably benign Het
Lman2 A G 13: 55,499,315 (GRCm39) S187P probably damaging Het
Mrpl38 T C 11: 116,029,288 (GRCm39) E76G possibly damaging Het
Mtx3 A G 13: 92,984,112 (GRCm39) I130V probably benign Het
Naf1 T G 8: 67,313,188 (GRCm39) probably benign Het
Notch1 C A 2: 26,350,019 (GRCm39) V2374L probably benign Het
Nrxn2 A G 19: 6,543,037 (GRCm39) D1087G probably benign Het
Nudt8 T C 19: 4,051,902 (GRCm39) F171S probably damaging Het
Or5an1 T G 19: 12,261,224 (GRCm39) F271V probably benign Het
Pds5a A T 5: 65,785,357 (GRCm39) C916* probably null Het
Phyhip A T 14: 70,699,334 (GRCm39) N46Y probably damaging Het
Pomt1 A G 2: 32,140,874 (GRCm39) Y502C possibly damaging Het
Prkcg A C 7: 3,352,097 (GRCm39) probably benign Het
Prl8a6 C T 13: 27,619,369 (GRCm39) E118K probably benign Het
Prpf39 T C 12: 65,104,689 (GRCm39) probably null Het
Ptprb A G 10: 116,205,262 (GRCm39) H2159R probably damaging Het
Ripor2 A T 13: 24,885,595 (GRCm39) D571V probably damaging Het
Rps19 C T 7: 24,584,552 (GRCm39) L34F probably benign Het
Rusc1 A G 3: 88,996,128 (GRCm39) S145P probably damaging Het
Scn4a T A 11: 106,230,051 (GRCm39) T586S probably damaging Het
Slc7a12 A G 3: 14,546,124 (GRCm39) S90G possibly damaging Het
Specc1l A G 10: 75,082,410 (GRCm39) D619G probably damaging Het
Src A G 2: 157,304,710 (GRCm39) D143G probably benign Het
Sst T C 16: 23,708,558 (GRCm39) N91S probably benign Het
Stxbp5l T A 16: 37,036,398 (GRCm39) I406F probably damaging Het
Thsd1 T A 8: 22,748,887 (GRCm39) I525N probably damaging Het
Ticam2 A T 18: 46,693,467 (GRCm39) F207I probably damaging Het
Tsc22d1 C A 14: 76,656,180 (GRCm39) N31K probably damaging Het
Tspan10 T C 11: 120,336,989 (GRCm39) V253A probably benign Het
Ttc33 A G 15: 5,237,924 (GRCm39) K99R possibly damaging Het
Vmn1r63 T A 7: 5,806,212 (GRCm39) N140I probably damaging Het
Yju2b C T 8: 84,990,498 (GRCm39) V45I probably benign Het
Zbtb25 A G 12: 76,395,903 (GRCm39) *440Q probably null Het
Zfhx4 T A 3: 5,461,978 (GRCm39) C1218S probably damaging Het
Zfp84 T A 7: 29,476,607 (GRCm39) I433N probably damaging Het
Other mutations in Nkx2-1
AlleleSourceChrCoordTypePredicted EffectPPH Score
R0617:Nkx2-1 UTSW 12 56,581,640 (GRCm39) missense possibly damaging 0.75
R1745:Nkx2-1 UTSW 12 56,580,529 (GRCm39) missense probably benign 0.00
R2230:Nkx2-1 UTSW 12 56,580,071 (GRCm39) nonsense probably null
R4691:Nkx2-1 UTSW 12 56,580,350 (GRCm39) missense probably benign 0.01
R4990:Nkx2-1 UTSW 12 56,581,724 (GRCm39) missense possibly damaging 0.72
R4991:Nkx2-1 UTSW 12 56,581,724 (GRCm39) missense possibly damaging 0.72
R7216:Nkx2-1 UTSW 12 56,581,587 (GRCm39) missense probably damaging 1.00
R7316:Nkx2-1 UTSW 12 56,581,583 (GRCm39) missense probably benign 0.18
R8401:Nkx2-1 UTSW 12 56,579,841 (GRCm39) missense probably damaging 0.99
R8854:Nkx2-1 UTSW 12 56,580,206 (GRCm39) missense probably benign 0.21
R9172:Nkx2-1 UTSW 12 56,581,752 (GRCm39) missense probably damaging 0.97
R9655:Nkx2-1 UTSW 12 56,581,802 (GRCm39) missense probably damaging 1.00
RF006:Nkx2-1 UTSW 12 56,580,332 (GRCm39) missense probably damaging 1.00
Z1176:Nkx2-1 UTSW 12 56,581,749 (GRCm39) missense probably damaging 0.97
Z1176:Nkx2-1 UTSW 12 56,580,469 (GRCm39) missense probably benign 0.00
Predicted Primers PCR Primer
(F):5'- CAGGGTTTGCCGTCTTTGAC -3'
(R):5'- CCCTTAAGTAGTTCGACGGCAC -3'

Sequencing Primer
(F):5'- TCTTTGACTAGGACCGGCAC -3'
(R):5'- TCTTTTGGGAAAGAGCACTAGGC -3'
Posted On 2014-10-15