Mutagenetix > Incidental Mutation

Incidental Mutation 'R4691:Nkx2-1'

354934

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

041942-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4691 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

56578741-56583570 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 56580350 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Leucine at position 197 (M197L)

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: M197L

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000001536
Gene: ENSMUSG00000001496
AA Change: M197L

Domain	Start	End	E-Value	Type
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: M197L

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000136103
Gene: ENSMUSG00000001496
AA Change: M197L

Domain	Start	End	E-Value	Type
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

Meta Mutation Damage Score

0.0968

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.1%
20x: 95.0%

Validation Efficiency

97% (70/72)

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: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca13	A	T	11: 9,384,195 (GRCm39)	R3882S	probably damaging	Het
Adamts2	G	T	11: 50,647,523 (GRCm39)	V299F	probably damaging	Het
Ankrd50	A	G	3: 38,537,159 (GRCm39)	S65P	probably benign	Het
Ap4e1	T	C	2: 126,903,791 (GRCm39)	C898R	probably benign	Het
Arel1	A	T	12: 84,977,023 (GRCm39)		probably null	Het
Bag6	T	A	17: 35,358,224 (GRCm39)	V164D	probably damaging	Het
C2cd5	A	G	6: 142,975,874 (GRCm39)	S769P	possibly damaging	Het
Cables1	C	T	18: 11,973,580 (GRCm39)	Q240*	probably null	Het
Ccnb1-ps	T	A	7: 41,755,516 (GRCm39)		noncoding transcript	Het
Ccz1	A	T	5: 143,928,380 (GRCm39)	I390N	possibly damaging	Het
Ceacam23	T	A	7: 17,642,891 (GRCm39)	S434T	possibly damaging	Het
Ces1a	T	C	8: 93,759,287 (GRCm39)	H283R	probably benign	Het
Clca3b	G	A	3: 144,544,853 (GRCm39)	T378I	probably benign	Het
Cpne2	A	T	8: 95,284,849 (GRCm39)	I342F	probably damaging	Het
Cyp2d9	A	G	15: 82,340,033 (GRCm39)	D141G	probably damaging	Het
Ddias	T	A	7: 92,508,024 (GRCm39)	K630N	probably damaging	Het
Dennd4b	A	G	3: 90,179,619 (GRCm39)	T626A	probably damaging	Het
Disc1	T	C	8: 125,875,186 (GRCm39)	V554A	possibly damaging	Het
Dnah10	A	G	5: 124,852,581 (GRCm39)	T1880A	probably damaging	Het
Dnase1l1	C	T	X: 73,320,644 (GRCm39)		probably null	Het
Epop	C	T	11: 97,519,719 (GRCm39)	G130D	possibly damaging	Het
Erap1	T	C	13: 74,821,811 (GRCm39)	L722P	probably damaging	Het
Eya4	T	A	10: 23,015,966 (GRCm39)	T334S	probably benign	Het
Ezr	T	C	17: 7,026,961 (GRCm39)	I5V	probably benign	Het
Fam53c	A	C	18: 34,901,743 (GRCm39)	E220A	probably damaging	Het
Galnt12	T	C	4: 47,104,143 (GRCm39)	S134P	probably damaging	Het
Gcfc2	T	A	6: 81,918,408 (GRCm39)	L366*	probably null	Het
Gins4	T	A	8: 23,727,075 (GRCm39)	D6V	probably benign	Het
Grid1	A	G	14: 35,291,514 (GRCm39)	H807R	probably benign	Het
H2-T22	GTTTT	GTTT	17: 36,352,462 (GRCm39)		probably null	Het
Ighv1-66	T	C	12: 115,556,929 (GRCm39)	Y51C	probably benign	Het
Inpp4b	A	T	8: 82,849,282 (GRCm39)	Y901F	probably damaging	Het
Irf2	T	A	8: 47,299,222 (GRCm39)	S339T	probably damaging	Het
Itgae	G	T	11: 73,010,345 (GRCm39)	G612*	probably null	Het
Kdr	T	C	5: 76,105,259 (GRCm39)	K1037R	possibly damaging	Het
Mro	A	T	18: 74,006,397 (GRCm39)	M115L	probably benign	Het
Myo5a	A	G	9: 75,087,438 (GRCm39)	E1098G	probably damaging	Het
Or7e165	T	C	9: 19,694,678 (GRCm39)	I83T	probably benign	Het
Pank2	T	A	2: 131,138,201 (GRCm39)	F430L	possibly damaging	Het
Pcx	T	A	19: 4,669,505 (GRCm39)	V794E	probably damaging	Het
Pdgfd	C	T	9: 6,288,556 (GRCm39)	P70L	probably damaging	Het
Pla2g4e	T	C	2: 120,004,781 (GRCm39)	Y521C	probably damaging	Het
Pou5f1	T	A	17: 35,817,028 (GRCm39)	F11Y	probably damaging	Het
Prdm9	A	G	17: 15,773,640 (GRCm39)	M252T	probably benign	Het
Ptk2b	C	T	14: 66,394,518 (GRCm39)	G859S	probably benign	Het
Rad51ap1	A	G	6: 126,904,516 (GRCm39)	S123P	probably benign	Het
Robo3	T	C	9: 37,336,514 (GRCm39)	E418G	probably damaging	Het
Sos2	C	T	12: 69,663,102 (GRCm39)	R631H	probably damaging	Het
Sp140l1	C	T	1: 85,066,521 (GRCm39)		probably benign	Het
St3gal2	C	T	8: 111,684,417 (GRCm39)	T25I	probably benign	Het
Stra6l	G	A	4: 45,882,851 (GRCm39)	A521T	probably benign	Het
Syt7	T	A	19: 10,403,845 (GRCm39)	L177Q	probably damaging	Het
Tet2	T	A	3: 133,191,844 (GRCm39)	Q863H	possibly damaging	Het
Tmem232	T	C	17: 65,572,237 (GRCm39)	K585E	possibly damaging	Het
Trpc6	A	C	9: 8,652,979 (GRCm39)	E595A	probably damaging	Het
Txnl1	A	G	18: 63,804,750 (GRCm39)	V248A	possibly damaging	Het
Vmn2r72	A	T	7: 85,387,119 (GRCm39)	L815*	probably null	Het
Vmn2r81	C	T	10: 79,129,211 (GRCm39)	Q701*	probably null	Het
Vps13c	T	C	9: 67,860,217 (GRCm39)	V2811A	possibly damaging	Het
Vsig10l2	T	C	9: 35,428,158 (GRCm39)	S106G	possibly damaging	Het
Zfp354a	A	G	11: 50,961,064 (GRCm39)	E425G	probably damaging	Het
Zfp617	A	T	8: 72,686,659 (GRCm39)	T330S	probably benign	Het
Zfp663	G	T	2: 165,201,050 (GRCm39)		probably benign	Het
Zfp84	T	C	7: 29,476,505 (GRCm39)	L399P	probably damaging	Het
Zfp869	A	T	8: 70,159,513 (GRCm39)	C353*	probably null	Het
Zscan22	C	T	7: 12,640,488 (GRCm39)	A85V	probably benign	Het

Other mutations in Nkx2-1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R2209:Nkx2-1	UTSW	12	56,580,293 (GRCm39)	missense	probably benign	0.15
R2230:Nkx2-1	UTSW	12	56,580,071 (GRCm39)	nonsense	probably null
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'- GTTTGCCGTCTTTGACTAGGACC -3'
(R):5'- TGAATATGAGTGGCATGGGC -3'

Sequencing Primer
(F):5'- TCTTTGACTAGGACCGGCAC -3'
(R):5'- TGAGCAAGAACATGGCC -3'

Posted On

2015-10-21