Mutagenetix > Incidental Mutation

Incidental Mutation 'R4991:Nkx2-1'

386209

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

042585-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4991 (G1)

Quality Score

120

Status

Validated

Chromosome

Chromosomal Location

56578741-56583570 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 56581724 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 41 (Y41C)

Ref Sequence

ENSEMBL: ENSMUSP00000136103 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000001536] [ENSMUST00000178477]

AlphaFold

P50220

Predicted Effect

possibly damaging
Transcript: ENSMUST00000001536
AA Change: Y41C

PolyPhen 2 Score 0.717 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000001536
Gene: ENSMUSG00000001496
AA Change: Y41C

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

possibly damaging
Transcript: ENSMUST00000178477
AA Change: Y41C

PolyPhen 2 Score 0.717 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000136103
Gene: ENSMUSG00000001496
AA Change: Y41C

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

Meta Mutation Damage Score

0.2152

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 95.7%
20x: 90.0%

Validation Efficiency

95% (73/77)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy4	G	T	14: 56,010,922 (GRCm39)	T665K	probably benign	Het
Adgrf3	C	T	5: 30,404,146 (GRCm39)	V369M	probably benign	Het
Als2	T	C	1: 59,246,927 (GRCm39)	K571E	probably benign	Het
Amer3	A	C	1: 34,627,822 (GRCm39)	D687A	probably benign	Het
Asb14	T	C	14: 26,637,015 (GRCm39)	S586P	probably damaging	Het
Catspere2	A	C	1: 177,925,987 (GRCm39)	I218L	probably benign	Het
Chmp4b	A	G	2: 154,534,545 (GRCm39)	E187G	probably benign	Het
Cox6b2	T	C	7: 4,755,160 (GRCm39)	D38G	probably damaging	Het
Cpm	G	A	10: 117,504,008 (GRCm39)	C138Y	probably damaging	Het
Csmd3	G	T	15: 47,864,874 (GRCm39)	P785Q	probably damaging	Het
Cstf1	A	G	2: 172,219,720 (GRCm39)	Y277C	probably damaging	Het
Cstf2t	T	A	19: 31,061,983 (GRCm39)	N506K	probably damaging	Het
Dmpk	C	G	7: 18,821,944 (GRCm39)	L301V	probably benign	Het
Ebf2	A	T	14: 67,627,106 (GRCm39)	T265S	possibly damaging	Het
Elmo1	T	C	13: 20,526,689 (GRCm39)	F413S	probably damaging	Het
Fbp1	C	T	13: 63,012,888 (GRCm39)	V102I	probably benign	Het
Gm19684	A	G	17: 36,438,364 (GRCm39)		probably benign	Het
Gm29106	T	C	1: 118,106,121 (GRCm39)	M37T	probably benign	Het
Grem2	A	G	1: 174,664,379 (GRCm39)	C157R	probably damaging	Het
Hdac5	T	A	11: 102,096,450 (GRCm39)	E252D	probably damaging	Het
Ifitm3	A	T	7: 140,590,372 (GRCm39)	F63I	probably damaging	Het
Igkv4-80	A	C	6: 68,993,649 (GRCm39)	S81A	probably benign	Het
Irx4	G	T	13: 73,413,626 (GRCm39)	R32L	probably benign	Het
Itgb1bp1	C	T	12: 21,324,849 (GRCm39)	G69D	probably damaging	Het
Kcnh3	A	G	15: 99,130,637 (GRCm39)	D418G	probably benign	Het
Kif1a	T	C	1: 93,006,530 (GRCm39)	T46A	probably benign	Het
Klk1b26	T	A	7: 43,665,673 (GRCm39)		probably null	Het
Lca5l	T	C	16: 95,960,932 (GRCm39)	E510G	possibly damaging	Het
Lrriq1	A	G	10: 103,036,420 (GRCm39)	I911T	probably damaging	Het
Mios	T	G	6: 8,215,847 (GRCm39)	S348A	probably benign	Het
Mog	T	C	17: 37,328,381 (GRCm39)		probably null	Het
Mtmr7	A	G	8: 41,007,386 (GRCm39)	S516P	probably damaging	Het
Nat8f4	T	C	6: 85,878,122 (GRCm39)	K134E	probably benign	Het
Nbeal2	C	T	9: 110,467,835 (GRCm39)	C451Y	probably damaging	Het
Nmnat1	G	A	4: 149,553,584 (GRCm39)	T176M	possibly damaging	Het
Nrxn3	T	A	12: 89,227,244 (GRCm39)	I293N	probably damaging	Het
Or5af2	T	C	11: 58,708,544 (GRCm39)	S237P	probably damaging	Het
Or5b97	T	G	19: 12,878,815 (GRCm39)	T110P	probably damaging	Het
Or5m8	A	G	2: 85,822,631 (GRCm39)	M157V	probably damaging	Het
Osgin1	A	G	8: 120,172,028 (GRCm39)	E274G	probably damaging	Het
Otof	G	A	5: 30,551,525 (GRCm39)	R343W	probably damaging	Het
Pcdha9	A	T	18: 37,131,398 (GRCm39)	I156F	probably damaging	Het
Pcsk4	A	G	10: 80,161,215 (GRCm39)	I233T	possibly damaging	Het
Pira12	T	G	7: 3,898,571 (GRCm39)	Q292H	probably benign	Het
Samd4	A	T	14: 47,311,467 (GRCm39)	S262C	probably damaging	Het
Snap91	T	C	9: 86,672,207 (GRCm39)		probably null	Het
Spata31d1a	T	C	13: 59,850,965 (GRCm39)	N388D	probably benign	Het
St3gal4	A	G	9: 34,964,432 (GRCm39)	V190A	possibly damaging	Het
Sv2b	T	C	7: 74,767,470 (GRCm39)	N642S	possibly damaging	Het
Svil	T	A	18: 5,056,810 (GRCm39)	I561K	probably benign	Het
Tmem201	A	T	4: 149,812,612 (GRCm39)	Y235N	possibly damaging	Het
Tpx2	T	C	2: 152,711,644 (GRCm39)	S60P	probably benign	Het
Trpa1	T	C	1: 14,980,970 (GRCm39)	Y144C	probably benign	Het
U90926	G	A	5: 92,357,879 (GRCm39)	P91S	probably benign	Het
Utp20	G	T	10: 88,582,796 (GRCm39)	H2780Q	probably benign	Het
Vmn1r215	T	G	13: 23,260,697 (GRCm39)	F246V	probably damaging	Het
Vmn2r72	A	G	7: 85,400,338 (GRCm39)	L237S	probably damaging	Het
Washc5	A	G	15: 59,215,929 (GRCm39)	S817P	probably damaging	Het
Zbtb24	A	G	10: 41,332,614 (GRCm39)		probably null	Het
Zfp212	G	A	6: 47,903,796 (GRCm39)	R127H	probably damaging	Het
Zfp268	C	A	4: 145,348,904 (GRCm39)	Q114K	probably benign	Het
Zfp740	G	T	15: 102,116,714 (GRCm39)		probably null	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
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
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'- CTCCTACACAAGGCTGTTCG -3'
(R):5'- CACCAGAATATTTGGCAAAGGG -3'

Sequencing Primer
(F):5'- TCACTTACTGGCGGGGAAG -3'
(R):5'- GGCTTCGCCTTCCCCCTC -3'

Posted On

2016-05-10