Mutagenetix > Incidental Mutation

Incidental Mutation 'R0597:Hif1a'

55136

Institutional Source

Beutler Lab

Gene Symbol

Hif1a

Ensembl Gene

ENSMUSG00000021109

Gene Name

hypoxia inducible factor 1, alpha subunit

Synonyms

bHLHe78, MOP1, HIF-1alpha, HIF1alpha

MMRRC Submission

038786-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0597 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

73948149-73994304 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 73989049 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 645 (S645R)

Ref Sequence

ENSEMBL: ENSMUSP00000106088 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021530] [ENSMUST00000110461]

AlphaFold

Q61221

Predicted Effect

probably benign
Transcript: ENSMUST00000021530
AA Change: S671R

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: S671R

Domain	Start	End	E-Value	Type
HLH	23	78	1.29e-8	SMART
PAS	87	153	1.05e-9	SMART
PAS	230	296	2.08e-8	SMART
PAC	302	345	6.85e-9	SMART
low complexity region	416	427	N/A	INTRINSIC
Pfam:HIF-1	564	594	5.4e-18	PFAM
low complexity region	621	645	N/A	INTRINSIC
Pfam:HIF-1a_CTAD	799	835	3.9e-25	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000110461
AA Change: S645R

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: S645R

Domain	Start	End	E-Value	Type
HLH	11	66	1.29e-8	SMART
PAS	75	141	1.05e-9	SMART
PAS	218	284	2.08e-8	SMART
PAC	290	333	6.85e-9	SMART
low complexity region	404	415	N/A	INTRINSIC
Pfam:HIF-1	536	569	6e-19	PFAM
low complexity region	595	619	N/A	INTRINSIC
Pfam:HIF-1a_CTAD	771	810	1.2e-25	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125308

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000157041

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000221427

Predicted Effect

probably benign
Transcript: ENSMUST00000221833

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.6%
3x: 99.0%
10x: 97.4%
20x: 94.1%

Validation Efficiency

97% (71/73)

MGI Phenotype

FUNCTION: This gene encodes the alpha subunit which, along with the beta subunit, forms a heterodimeric transcription factor that regulates the cellular and developmental response to reduced oxygen tension. The transcription factor has been shown to regulate genes involved in several biological processes, including erythropoiesis and angiogenesis which aid in increased delivery of oxygen to hypoxic regions. The transcription factor also plays a role in the induction of genes involved in cell proliferation and survival, energy metabolism, apoptosis, and glucose and iron metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]
PHENOTYPE: Homozygous null mutants die during embryonic development with severe cardiovascular malformations, neural tube defects, cephalic defects, reduced somite number and increased hypoxia. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 70 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy10	T	C	1: 165,352,631 (GRCm39)		probably null	Het
Anxa11	T	C	14: 25,874,652 (GRCm39)	I221T	probably damaging	Het
Arhgap33	C	G	7: 30,225,871 (GRCm39)	R565P	probably damaging	Het
Bmpr2	T	C	1: 59,880,584 (GRCm39)		probably benign	Het
Btn2a2	T	A	13: 23,670,580 (GRCm39)	H51L	probably benign	Het
Casz1	T	C	4: 149,028,851 (GRCm39)	S1099P	probably benign	Het
Cnot4	A	G	6: 35,028,438 (GRCm39)	S393P	possibly damaging	Het
Cntnap5a	T	C	1: 116,112,191 (GRCm39)		probably benign	Het
Cobl	T	C	11: 12,204,699 (GRCm39)	T586A	probably benign	Het
Crocc	T	C	4: 140,747,224 (GRCm39)	K1528R	probably benign	Het
Crocc	A	G	4: 140,744,382 (GRCm39)	L1838P	probably benign	Het
Dact2	A	G	17: 14,417,303 (GRCm39)	V299A	probably benign	Het
Dapk1	C	A	13: 60,909,198 (GRCm39)	N1270K	probably benign	Het
Ddx41	T	C	13: 55,680,819 (GRCm39)	Y375C	probably damaging	Het
Dock5	T	A	14: 68,022,383 (GRCm39)		probably null	Het
Dyrk4	T	G	6: 126,863,612 (GRCm39)		probably null	Het
Eno1b	T	C	18: 48,180,806 (GRCm39)	I328T	probably benign	Het
Fam210b	A	G	2: 172,187,773 (GRCm39)		probably benign	Het
Fbxl13	A	G	5: 21,819,712 (GRCm39)	I229T	probably benign	Het
Fbxo39	A	G	11: 72,207,747 (GRCm39)	D33G	probably damaging	Het
Fbxw11	A	G	11: 32,670,496 (GRCm39)	E120G	probably damaging	Het
Fbxw2	A	T	2: 34,701,032 (GRCm39)	L261Q	probably damaging	Het
Gm5800	A	C	14: 51,953,461 (GRCm39)	N51K	probably benign	Het
Gm6899	A	G	11: 26,543,768 (GRCm39)		probably benign	Het
Gpx8	T	C	13: 113,182,035 (GRCm39)	T133A	possibly damaging	Het
Grin3a	C	T	4: 49,665,351 (GRCm39)	V1095M	probably damaging	Het
Grip2	T	C	6: 91,773,178 (GRCm39)		probably benign	Het
Hacd4	A	G	4: 88,355,757 (GRCm39)	F43L	probably damaging	Het
Hipk3	A	G	2: 104,263,982 (GRCm39)	S839P	possibly damaging	Het
Idi2l	C	A	13: 8,990,802 (GRCm39)		probably benign	Het
Il16	A	T	7: 83,327,183 (GRCm39)		probably benign	Het
Il3ra	T	A	14: 14,351,166 (GRCm38)		probably null	Het
Il5ra	A	G	6: 106,721,296 (GRCm39)	M1T	probably null	Het
Klra2	G	A	6: 131,197,148 (GRCm39)	R251C	probably benign	Het
Lamc2	C	T	1: 153,009,367 (GRCm39)	V813M	probably benign	Het
Lbr	A	G	1: 181,659,778 (GRCm39)	V139A	probably benign	Het
Lrp5	T	C	19: 3,650,777 (GRCm39)	D1219G	possibly damaging	Het
Map3k6	C	T	4: 132,972,863 (GRCm39)	P341S	possibly damaging	Het
Mcts2	A	G	2: 152,529,609 (GRCm39)	E140G	probably benign	Het
Med1	T	C	11: 98,060,264 (GRCm39)	M222V	probably benign	Het
Mef2a	G	T	7: 66,884,896 (GRCm39)	S406*	probably null	Het
Muc19	A	T	15: 91,784,696 (GRCm39)		noncoding transcript	Het
Nr1h2	A	G	7: 44,201,684 (GRCm39)		probably benign	Het
Or13j1	A	T	4: 43,706,592 (GRCm39)		probably null	Het
Or2w6	C	A	13: 21,843,316 (GRCm39)	R59L	probably damaging	Het
Or56a42-ps1	A	G	7: 104,777,425 (GRCm39)	V73A	possibly damaging	Het
Or5ac23	A	T	16: 59,149,123 (GRCm39)	F250I	probably damaging	Het
P4hb	G	A	11: 120,459,070 (GRCm39)	T141I	possibly damaging	Het
Polr3a	A	G	14: 24,534,202 (GRCm39)	V101A	probably benign	Het
Pou4f2	A	G	8: 79,161,869 (GRCm39)	S245P	probably benign	Het
Pramel26	G	T	4: 143,539,222 (GRCm39)	N90K	probably damaging	Het
Rnpep	A	G	1: 135,200,157 (GRCm39)	V266A	probably damaging	Het
Scly	G	A	1: 91,237,555 (GRCm39)	G206R	probably damaging	Het
Sec14l3	A	T	11: 4,024,814 (GRCm39)	K254N	probably damaging	Het
Sgpp1	A	T	12: 75,781,874 (GRCm39)	I155N	probably damaging	Het
Slc22a14	A	G	9: 119,001,190 (GRCm39)	L468P	probably damaging	Het
Slc22a27	A	G	19: 7,843,249 (GRCm39)	F377L	probably benign	Het
Slc44a3	T	C	3: 121,253,719 (GRCm39)	I625V	probably benign	Het
Slc47a2	A	T	11: 61,200,802 (GRCm39)	I373N	probably damaging	Het
Slfn10-ps	A	T	11: 82,926,479 (GRCm39)		noncoding transcript	Het
Smarcd1	T	A	15: 99,608,975 (GRCm39)	I383N	probably damaging	Het
Sort1	A	G	3: 108,246,226 (GRCm39)	D401G	probably damaging	Het
Sprr2a3	G	T	3: 92,195,897 (GRCm39)	M1I	probably null	Het
Sycp2	A	C	2: 177,998,373 (GRCm39)	V1049G	possibly damaging	Het
Tecrl	T	A	5: 83,502,775 (GRCm39)	K10*	probably null	Het
Tnpo3	A	T	6: 29,578,564 (GRCm39)	C303*	probably null	Het
Vmn2r23	A	G	6: 123,706,680 (GRCm39)	I503M	probably benign	Het
Zbtb8os	T	A	4: 129,240,670 (GRCm39)	I164N	probably damaging	Het
Zfp292	T	C	4: 34,807,399 (GRCm39)	N1882D	probably benign	Het
Zfp91	T	C	19: 12,747,459 (GRCm39)	I555V	possibly damaging	Het

Other mutations in Hif1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00979:Hif1a	APN	12	73,988,784 (GRCm39)	missense	probably damaging	1.00
IGL01396:Hif1a	APN	12	73,987,307 (GRCm39)	missense	probably benign	0.00
IGL02230:Hif1a	APN	12	73,979,224 (GRCm39)	missense	probably damaging	1.00
IGL02561:Hif1a	APN	12	73,988,980 (GRCm39)	missense	possibly damaging	0.52
IGL02698:Hif1a	APN	12	73,977,545 (GRCm39)	critical splice donor site	probably null
IGL03027:Hif1a	APN	12	73,987,251 (GRCm39)	missense	probably benign	0.03
lightweight	UTSW	12	73,988,574 (GRCm39)	missense	probably damaging	1.00
R0614:Hif1a	UTSW	12	73,992,405 (GRCm39)	missense	probably damaging	1.00
R0678:Hif1a	UTSW	12	73,990,965 (GRCm39)	splice site	probably null
R0967:Hif1a	UTSW	12	73,984,444 (GRCm39)	missense	possibly damaging	0.91
R1351:Hif1a	UTSW	12	73,987,235 (GRCm39)	missense	probably benign	0.00
R1387:Hif1a	UTSW	12	73,989,066 (GRCm39)	missense	possibly damaging	0.95
R1858:Hif1a	UTSW	12	73,990,929 (GRCm39)	missense	probably benign
R2105:Hif1a	UTSW	12	73,984,519 (GRCm39)	missense	probably damaging	1.00
R2194:Hif1a	UTSW	12	73,977,521 (GRCm39)	missense	probably damaging	0.98
R4825:Hif1a	UTSW	12	73,979,175 (GRCm39)	missense	probably damaging	1.00
R4924:Hif1a	UTSW	12	73,986,331 (GRCm39)	missense	probably damaging	1.00
R5386:Hif1a	UTSW	12	73,990,867 (GRCm39)	missense	probably benign	0.02
R5594:Hif1a	UTSW	12	73,984,566 (GRCm39)	nonsense	probably null
R5722:Hif1a	UTSW	12	73,988,533 (GRCm39)	missense	probably benign	0.00
R5818:Hif1a	UTSW	12	73,986,338 (GRCm39)	missense	possibly damaging	0.64
R5831:Hif1a	UTSW	12	73,988,918 (GRCm39)	missense	probably benign
R6026:Hif1a	UTSW	12	73,979,055 (GRCm39)	missense	probably damaging	1.00
R6059:Hif1a	UTSW	12	73,988,574 (GRCm39)	missense	probably damaging	1.00
R6084:Hif1a	UTSW	12	73,988,616 (GRCm39)	missense	probably damaging	0.99
R6818:Hif1a	UTSW	12	73,992,337 (GRCm39)	nonsense	probably null
R6878:Hif1a	UTSW	12	73,975,055 (GRCm39)	missense	possibly damaging	0.49
R8028:Hif1a	UTSW	12	73,988,801 (GRCm39)	missense	probably benign	0.27
R8286:Hif1a	UTSW	12	73,992,022 (GRCm39)	intron	probably benign
R8322:Hif1a	UTSW	12	73,986,373 (GRCm39)	missense	probably benign
R8414:Hif1a	UTSW	12	73,984,428 (GRCm39)	missense	probably benign	0.00
R8729:Hif1a	UTSW	12	73,990,902 (GRCm39)	missense	probably damaging	1.00
R9030:Hif1a	UTSW	12	73,983,010 (GRCm39)	missense	probably damaging	1.00
R9087:Hif1a	UTSW	12	73,989,099 (GRCm39)	missense	probably benign	0.01
R9093:Hif1a	UTSW	12	73,979,111 (GRCm39)	missense	probably benign	0.12
R9300:Hif1a	UTSW	12	73,987,302 (GRCm39)	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- CACAGTTACTGGGTTCCAGCAGAC -3'
(R):5'- AGCAGCATGAAGAGATTCCTGGC -3'

Sequencing Primer
(F):5'- GGTTCCAGCAGACCCAGTTAC -3'
(R):5'- GTTGGAAAACATCTCTGACCTC -3'

Posted On

2013-07-11