Mutagenetix > Incidental Mutation

Incidental Mutation 'R1498:Hnf1a'

169022

Institutional Source

Beutler Lab

Gene Symbol

Hnf1a

Ensembl Gene

ENSMUSG00000029556

Gene Name

HNF1 homeobox A

Synonyms

hepatocyte nuclear factor 1, Tcf1, HNF1, HNF1[a], Hnf-1, HNF1-alpha, LFB1, Hnf1alpha

MMRRC Submission

039549-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.865) question?

Stock #

R1498 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

115087039-115109121 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 115108596 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 103 (V103A)

Ref Sequence

ENSEMBL: ENSMUSP00000031535 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000031535] [ENSMUST00000176550] [ENSMUST00000176911]

AlphaFold

P22361

PDB Structure

CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE DIMERIZATION DOMAIN OF HNF-1 ALPHA AND THE COACTIVATOR DCOH [X-RAY DIFFRACTION]
HNF-1ALPHA DIMERIZATION DOMAIN, WITH SELENOMETHIONINE SUBSTITUED AT LEU 12 [X-RAY DIFFRACTION]
DIMERIZATION DOMAIN OF HNF-1ALPHA WITH A LEU 13 SELENOMETHIONINE SUBSTITUTION [X-RAY DIFFRACTION]
WILD-TYPE HNF-1ALPHA DIMERIZATION DOMAIN [X-RAY DIFFRACTION]
Crystal Structure of Dimerization Domain (1-33) of HNF-1alpha [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000031535
AA Change: V103A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000031535
Gene: ENSMUSG00000029556
AA Change: V103A

Domain	Start	End	E-Value	Type
Pfam:HNF-1_N	8	168	4e-57	PFAM
HOX	199	282	1.85e-7	SMART
low complexity region	288	297	N/A	INTRINSIC
Blast:HOX	394	439	7e-20	BLAST
Pfam:HNF-1A_C	540	627	3.4e-38	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125010

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129609

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000131845

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000138108

Predicted Effect

possibly damaging
Transcript: ENSMUST00000176550
AA Change: V103A

PolyPhen 2 Score 0.901 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000135678
Gene: ENSMUSG00000029556
AA Change: V103A

Domain	Start	End	E-Value	Type
Pfam:HNF-1_N	1	176	4e-86	PFAM
Blast:HOX	199	238	2e-20	BLAST
SCOP:d1lfb__	203	238	2e-18	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000176911
AA Change: V103A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000135539
Gene: ENSMUSG00000029556
AA Change: V103A

Domain	Start	End	E-Value	Type
Pfam:HNF-1_N	1	118	6.4e-32	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000202592

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184027

Meta Mutation Damage Score

0.0944

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.2%
20x: 92.6%

Validation Efficiency

97% (83/86)

MGI Phenotype

FUNCTION: This gene encodes a hepatic transcription factor. The encoded protein is not a member of the T-cell factor family, and is distinct from T-cell specific transcription factor 7 which has also been referred to by the symbol Tcf1. [provided by RefSeq, Jul 2008]
PHENOTYPE: Most homozygous null mutants die at 3-6 weeks from progressive wasting syndrome, liver and renal dysfunction and type II diabetes. Mutants have little or no phenylalanine hydroxylase, albumin, alpha 1-antitrypsin and secreted insulin. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acly	A	G	11: 100,374,627 (GRCm39)	S799P	probably benign	Het
Acvr1b	T	C	15: 101,091,891 (GRCm39)	F57S	probably benign	Het
Adamts5	T	A	16: 85,696,990 (GRCm39)	T56S	possibly damaging	Het
Adrb2	T	C	18: 62,312,004 (GRCm39)	T274A	probably damaging	Het
Agr3	A	T	12: 35,984,379 (GRCm39)		probably null	Het
Ankrd6	A	G	4: 32,810,289 (GRCm39)	M405T	probably benign	Het
Aoc1l2	A	G	6: 48,908,305 (GRCm39)	H435R	probably benign	Het
Aqp5	T	C	15: 99,491,128 (GRCm39)	I60T	probably damaging	Het
Arf5	G	T	6: 28,426,153 (GRCm39)	R180L	probably benign	Het
Asap3	A	G	4: 135,966,505 (GRCm39)	N528D	probably benign	Het
Atmin	G	A	8: 117,681,540 (GRCm39)	E180K	probably benign	Het
Bcl11a	A	T	11: 24,114,005 (GRCm39)	E449D	probably damaging	Het
Cep128	A	T	12: 91,333,191 (GRCm39)	F25I	probably benign	Het
Cfp	GCAC	GC	X: 20,795,905 (GRCm39)		probably null	Het
Chpt1	T	A	10: 88,312,966 (GRCm39)	Y282F	possibly damaging	Het
Cul7	A	G	17: 46,966,636 (GRCm39)	D355G	probably benign	Het
Daxx	T	C	17: 34,131,227 (GRCm39)	Y385H	probably damaging	Het
Dnah2	A	C	11: 69,411,493 (GRCm39)		probably null	Het
Dscc1	CTGAATGAAT	CTGAAT	15: 54,943,572 (GRCm39)		probably benign	Het
Erc2	T	A	14: 28,024,855 (GRCm39)	M578K	probably benign	Het
Evc	T	A	5: 37,481,044 (GRCm39)	H267L	possibly damaging	Het
Exosc10	A	C	4: 148,666,243 (GRCm39)	Q837P	possibly damaging	Het
Fasn	G	A	11: 120,706,245 (GRCm39)	T1033I	probably damaging	Het
Fat1	C	A	8: 45,478,521 (GRCm39)	Y2522*	probably null	Het
Fbxw8	G	A	5: 118,203,850 (GRCm39)		probably benign	Het
Fyn	A	G	10: 39,408,120 (GRCm39)	D321G	possibly damaging	Het
Grm6	G	A	11: 50,748,083 (GRCm39)	V398M	probably damaging	Het
Gtpbp1	T	A	15: 79,603,222 (GRCm39)		probably null	Het
Hsp90aa1	A	T	12: 110,662,122 (GRCm39)		probably null	Het
Iqgap2	C	T	13: 95,783,313 (GRCm39)	V1288I	probably benign	Het
Irx5	A	G	8: 93,086,514 (GRCm39)	D199G	probably damaging	Het
Klrh1	A	G	6: 129,748,703 (GRCm39)	S105P	probably damaging	Het
Krt9	G	T	11: 100,079,195 (GRCm39)	C732*	probably null	Het
Lifr	T	C	15: 7,220,099 (GRCm39)	S910P	probably damaging	Het
Lrig1	G	A	6: 94,604,968 (GRCm39)	A209V	possibly damaging	Het
Lrrk1	T	A	7: 65,952,419 (GRCm39)	R506*	probably null	Het
Lyst	T	A	13: 13,824,960 (GRCm39)	I1525K	possibly damaging	Het
Mad2l1	C	T	6: 66,516,826 (GRCm39)	Q173*	probably null	Het
Mcoln1	T	A	8: 3,562,861 (GRCm39)	I524N	probably damaging	Het
Mmp3	A	T	9: 7,446,967 (GRCm39)	D49V	possibly damaging	Het
Morc3	A	T	16: 93,650,743 (GRCm39)	N321I	probably damaging	Het
Mrpl48	T	C	7: 100,195,695 (GRCm39)		probably benign	Het
Myo6	T	A	9: 80,214,961 (GRCm39)	D1231E	probably damaging	Het
Nlrc4	A	G	17: 74,753,408 (GRCm39)	I325T	probably benign	Het
Or1j19	A	T	2: 36,677,358 (GRCm39)	I274F	probably damaging	Het
Or2ag17	T	C	7: 106,389,623 (GRCm39)	Y195C	possibly damaging	Het
Or4f61	A	T	2: 111,922,938 (GRCm39)	M36K	probably benign	Het
Or8c16	C	G	9: 38,130,676 (GRCm39)	P183A	probably damaging	Het
Or8k32	A	G	2: 86,368,902 (GRCm39)	V117A	probably benign	Het
Parvg	T	A	15: 84,218,832 (GRCm39)	S230T	possibly damaging	Het
Pcca	T	C	14: 122,854,230 (GRCm39)	I118T	probably damaging	Het
Pde6a	A	G	18: 61,365,932 (GRCm39)	N219S	possibly damaging	Het
Phldb1	G	T	9: 44,612,915 (GRCm39)	P935Q	possibly damaging	Het
Plppr5	T	C	3: 117,456,261 (GRCm39)	S261P	probably damaging	Het
Ppl	T	C	16: 4,922,629 (GRCm39)	N260S	probably benign	Het
Ppp1r3e	A	T	14: 55,113,882 (GRCm39)	H263Q	probably benign	Het
Ppp3cb	T	C	14: 20,559,567 (GRCm39)		probably null	Het
Ppt2	A	T	17: 34,842,075 (GRCm39)	D185E	probably benign	Het
Prr27	A	T	5: 87,998,600 (GRCm39)		probably benign	Het
Ptcd3	A	T	6: 71,870,479 (GRCm39)	V327E	probably damaging	Het
Pwwp4a	G	T	X: 72,171,261 (GRCm39)	G218C	probably damaging	Het
Rsf1	GCG	GCGACG	7: 97,229,114 (GRCm39)		probably benign	Het
Rtp1	A	T	16: 23,249,970 (GRCm39)	M112L	probably benign	Het
Slc22a5	A	T	11: 53,760,140 (GRCm39)	L392Q	probably damaging	Het
Slc6a7	A	G	18: 61,129,764 (GRCm39)	I614T	probably benign	Het
Slu7	C	A	11: 43,329,044 (GRCm39)	P89T	possibly damaging	Het
Smarcc2	T	C	10: 128,318,061 (GRCm39)	V618A	probably benign	Het
Sorl1	C	T	9: 41,952,369 (GRCm39)	R729Q	probably damaging	Het
Sptbn2	T	C	19: 4,794,274 (GRCm39)	F1493L	possibly damaging	Het
Sulf1	C	T	1: 12,918,574 (GRCm39)	T66I	probably damaging	Het
Tgtp2	A	G	11: 48,950,165 (GRCm39)	Y136H	probably damaging	Het
Tmem117	T	C	15: 94,536,242 (GRCm39)	F92S	probably damaging	Het
Tmprss9	T	A	10: 80,730,934 (GRCm39)	V820E	probably benign	Het
Tpcn2	A	G	7: 144,822,648 (GRCm39)	Y266H	probably damaging	Het
Trat1	A	G	16: 48,555,304 (GRCm39)	S143P	probably benign	Het
Vmn1r49	T	A	6: 90,049,298 (GRCm39)	R235W	probably damaging	Het
Vmn1r71	A	T	7: 10,482,575 (GRCm39)	C38S	probably benign	Het
Vmn2r6	T	A	3: 64,463,890 (GRCm39)	T315S	probably damaging	Het
Wdr36	A	G	18: 32,986,021 (GRCm39)	D575G	possibly damaging	Het
Zfp292	G	T	4: 34,805,397 (GRCm39)	A2549E	possibly damaging	Het
Zfp354a	A	T	11: 50,961,073 (GRCm39)	H426L	probably damaging	Het
Zfp407	C	T	18: 84,577,898 (GRCm39)	A1072T	probably benign	Het
Zfp648	T	A	1: 154,081,119 (GRCm39)	I426N	probably damaging	Het
Zfp87	T	C	13: 74,520,736 (GRCm39)	N114S	probably benign	Het

Other mutations in Hnf1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01798:Hnf1a	APN	5	115,091,732 (GRCm39)	missense	probably damaging	1.00
IGL02192:Hnf1a	APN	5	115,098,177 (GRCm39)	missense	probably damaging	1.00
IGL03053:Hnf1a	APN	5	115,108,792 (GRCm39)	missense	probably benign	0.00
R0522:Hnf1a	UTSW	5	115,088,747 (GRCm39)	splice site	probably benign
R0543:Hnf1a	UTSW	5	115,088,803 (GRCm39)	missense	probably benign
R1827:Hnf1a	UTSW	5	115,098,254 (GRCm39)	missense	probably damaging	1.00
R1852:Hnf1a	UTSW	5	115,108,770 (GRCm39)	missense	probably damaging	1.00
R2408:Hnf1a	UTSW	5	115,098,070 (GRCm39)	splice site	probably null
R2898:Hnf1a	UTSW	5	115,098,106 (GRCm39)	nonsense	probably null
R4050:Hnf1a	UTSW	5	115,108,633 (GRCm39)	missense	probably damaging	1.00
R4627:Hnf1a	UTSW	5	115,093,930 (GRCm39)	missense	probably damaging	1.00
R4859:Hnf1a	UTSW	5	115,093,311 (GRCm39)	missense	possibly damaging	0.84
R4873:Hnf1a	UTSW	5	115,108,732 (GRCm39)	missense	probably benign	0.00
R4875:Hnf1a	UTSW	5	115,108,732 (GRCm39)	missense	probably benign	0.00
R6488:Hnf1a	UTSW	5	115,094,020 (GRCm39)	missense	probably benign
R7134:Hnf1a	UTSW	5	115,091,446 (GRCm39)	missense	probably damaging	1.00
R7999:Hnf1a	UTSW	5	115,098,233 (GRCm39)	nonsense	probably null
R8085:Hnf1a	UTSW	5	115,108,732 (GRCm39)	missense	probably benign	0.00
R8093:Hnf1a	UTSW	5	115,093,336 (GRCm39)	missense	probably benign
R8360:Hnf1a	UTSW	5	115,091,391 (GRCm39)	missense	possibly damaging	0.93
R8539:Hnf1a	UTSW	5	115,108,576 (GRCm39)	critical splice donor site	probably null
R9047:Hnf1a	UTSW	5	115,088,882 (GRCm39)	missense	probably benign
X0067:Hnf1a	UTSW	5	115,093,539 (GRCm39)	missense	possibly damaging	0.52
Z1176:Hnf1a	UTSW	5	115,088,183 (GRCm39)	frame shift	probably null

Predicted Primers

PCR Primer
(F):5'- AGGTTCGGCAAGAAGCCCTTAAC -3'
(R):5'- GCTCCAATGTAAACAGAGCAGGCAG -3'

Sequencing Primer
(F):5'- GCCCTTAACCACCAGCCTG -3'
(R):5'- CATGGTTTCTAAGCTGAGCCAG -3'

Posted On

2014-04-13