Mutagenetix > Incidental Mutation

Incidental Mutation 'R4990:Nkx2-1'

386150

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

042584-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4990 (G1)

Quality Score

109

Status

Not 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: 99.3%
3x: 98.6%
10x: 97.0%
20x: 94.4%

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca12	T	C	1: 71,334,098 (GRCm39)	I1135V	possibly damaging	Het
Abca14	G	A	7: 119,911,388 (GRCm39)	R1324K	probably benign	Het
Amer3	A	C	1: 34,627,822 (GRCm39)	D687A	probably benign	Het
Aplnr	G	A	2: 84,967,721 (GRCm39)	V249M	probably damaging	Het
Atg16l1	A	G	1: 87,717,091 (GRCm39)	K471R	probably benign	Het
Cacna1b	A	G	2: 24,568,886 (GRCm39)		probably null	Het
Catspere2	A	C	1: 177,925,987 (GRCm39)	I218L	probably benign	Het
Ccdc152	A	G	15: 3,330,639 (GRCm39)	I12T	probably benign	Het
Cds1	A	G	5: 101,946,245 (GRCm39)	Y148C	probably damaging	Het
Cenpe	T	A	3: 134,962,401 (GRCm39)	L1989Q	probably damaging	Het
Cep295	T	C	9: 15,243,434 (GRCm39)	Q1674R	probably damaging	Het
D930020B18Rik	C	G	10: 121,490,666 (GRCm39)	P89A	probably damaging	Het
D930020B18Rik	C	T	10: 121,490,667 (GRCm39)	P89L	probably damaging	Het
Dock2	T	C	11: 34,586,078 (GRCm39)	M535V	probably damaging	Het
Dscam	A	G	16: 96,626,715 (GRCm39)	V398A	probably benign	Het
Elmo1	T	C	13: 20,526,689 (GRCm39)	F413S	probably damaging	Het
Emb	T	A	13: 117,401,046 (GRCm39)	N198K	probably damaging	Het
Eno3	A	G	11: 70,549,473 (GRCm39)	D98G	probably damaging	Het
Fbp1	C	T	13: 63,012,888 (GRCm39)	V102I	probably benign	Het
Fbxw18	T	C	9: 109,517,461 (GRCm39)	E414G	probably damaging	Het
Grem2	A	G	1: 174,664,379 (GRCm39)	C157R	probably damaging	Het
Hnrnpr	G	A	4: 136,063,609 (GRCm39)	V239I	probably damaging	Het
Hnrnpr	A	G	4: 136,056,690 (GRCm39)	E230G	probably damaging	Het
Ipo11	A	T	13: 106,997,395 (GRCm39)	I688K	probably benign	Het
Irx4	G	T	13: 73,413,626 (GRCm39)	R32L	probably benign	Het
Kcnh7	T	C	2: 62,564,632 (GRCm39)	N876D	probably benign	Het
Klk1b26	T	A	7: 43,665,673 (GRCm39)		probably null	Het
Lrp2	G	T	2: 69,311,732 (GRCm39)	T2582K	probably benign	Het
Lrriq1	A	G	10: 103,036,420 (GRCm39)	I911T	probably damaging	Het
Megf6	A	G	4: 154,351,683 (GRCm39)	E1132G	possibly damaging	Het
Mesp1	A	G	7: 79,442,669 (GRCm39)	Y203H	probably damaging	Het
Ms4a4a	T	C	19: 11,356,201 (GRCm39)	S29P	probably benign	Het
Nbeal2	A	C	9: 110,463,871 (GRCm39)	C1174G	probably benign	Het
Neb	C	T	2: 52,145,558 (GRCm39)	V2989I	probably benign	Het
Nrxn3	T	A	12: 89,227,244 (GRCm39)	I293N	probably damaging	Het
Nt5e	A	G	9: 88,237,646 (GRCm39)	N192S	probably benign	Het
Ntng1	A	T	3: 110,042,577 (GRCm39)		probably null	Het
Or13a17	G	A	7: 140,271,360 (GRCm39)	E181K	probably damaging	Het
Or3a1d	A	G	11: 74,238,023 (GRCm39)	I129T	probably damaging	Het
Or4c110	A	T	2: 88,831,816 (GRCm39)	I272K	probably damaging	Het
Or4c15b	A	T	2: 89,113,671 (GRCm39)		probably null	Het
Panx1	A	G	9: 14,921,513 (GRCm39)	Y121H	probably damaging	Het
Pcsk4	A	G	10: 80,161,215 (GRCm39)	I233T	possibly damaging	Het
Pgm3	T	A	9: 86,440,465 (GRCm39)	I409F	probably damaging	Het
Plg	T	C	17: 12,630,397 (GRCm39)	Y645H	probably benign	Het
Pon3	T	C	6: 5,221,619 (GRCm39)	H337R	probably benign	Het
Rasa2	A	G	9: 96,474,042 (GRCm39)	I162T	probably benign	Het
Ror1	A	G	4: 100,299,161 (GRCm39)	I845V	probably benign	Het
Rpl4	T	C	9: 64,082,167 (GRCm39)	V22A	probably benign	Het
Ryr3	T	C	2: 112,740,318 (GRCm39)	N531S	probably damaging	Het
Ryr3	G	T	2: 112,466,122 (GRCm39)	Q4746K	probably damaging	Het
Sbno1	A	T	5: 124,538,228 (GRCm39)	F571I	probably damaging	Het
Scarf1	T	C	11: 75,416,841 (GRCm39)	V761A	probably benign	Het
Sec22b	T	G	3: 97,828,427 (GRCm39)		probably null	Het
Slc45a2	A	G	15: 11,001,236 (GRCm39)	M112V	probably benign	Het
Snai3	G	A	8: 123,183,071 (GRCm39)	T158M	possibly damaging	Het
Spata31d1a	T	C	13: 59,850,965 (GRCm39)	N388D	probably benign	Het
Speer1e	A	T	5: 11,236,381 (GRCm39)	E138V	probably 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
Trappc11	A	T	8: 47,943,930 (GRCm39)	D1127E	probably benign	Het
Triobp	C	A	15: 78,851,205 (GRCm39)	A453D	probably benign	Het
Tubd1	T	C	11: 86,448,665 (GRCm39)	L295P	probably damaging	Het
Ulk4	C	T	9: 121,021,852 (GRCm39)	V620I	probably benign	Het
Vmn2r39	A	G	7: 9,026,675 (GRCm39)	I442T	probably benign	Het
Wwc1	T	C	11: 35,767,393 (GRCm39)	T413A	probably benign	Het
Zfp131	A	C	13: 120,244,449 (GRCm39)	V77G	probably damaging	Het
Zfyve26	T	C	12: 79,334,607 (GRCm39)	D137G	probably damaging	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
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'- CACTCCTACACAAGGCTGTTC -3'
(R):5'- ATCGGCGTTAAGGTAACACC -3'

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

Posted On

2016-05-10