Mutagenetix > Incidental Mutation

Incidental Mutation 'R2105:Hif1a'

230897

Institutional Source

Beutler Lab

Gene Symbol

Hif1a

Ensembl Gene

ENSMUSG00000021109

Gene Name

hypoxia inducible factor 1, alpha subunit

Synonyms

bHLHe78, HIF1alpha, MOP1, HIF-1alpha

MMRRC Submission

040109-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2105 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

73901375-73947530 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 73937745 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 313 (Y313N)

Ref Sequence

ENSEMBL: ENSMUSP00000106088 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021530] [ENSMUST00000110461] [ENSMUST00000110464]

AlphaFold

Q61221

Predicted Effect

probably damaging
Transcript: ENSMUST00000021530
AA Change: Y325N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: Y325N

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 damaging
Transcript: ENSMUST00000110461
AA Change: Y313N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: Y313N

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

probably benign
Transcript: ENSMUST00000110464

SMART Domains

Protein: ENSMUSP00000106091
Gene: ENSMUSG00000021109

Domain	Start	End	E-Value	Type
HLH	23	78	1.29e-8	SMART
PAS	87	153	1.05e-9	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125308

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000157041

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000221427

Predicted Effect

unknown
Transcript: ENSMUST00000221833
AA Change: Y31N

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.5%

Validation Efficiency

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	C	T	6: 121,673,500	P1189L	probably benign	Het
Acbd4	G	A	11: 103,104,439	D57N	probably damaging	Het
Acot4	A	T	12: 84,038,742	M78L	probably damaging	Het
Ago1	A	T	4: 126,461,788	M76K	probably benign	Het
Agrn	G	T	4: 156,177,299	Y511*	probably null	Het
Arhgef15	A	T	11: 68,947,681		probably null	Het
Atp1a3	A	T	7: 24,989,853	M594K	probably damaging	Het
Atp4a	G	A	7: 30,720,368		probably null	Het
Bckdk	T	A	7: 127,907,317	I272N	probably damaging	Het
Bod1l	A	G	5: 41,832,279	V367A	probably benign	Het
C1galt1c1	T	C	X: 38,631,268	M284V	possibly damaging	Het
Cenpk	T	A	13: 104,229,597	C4*	probably null	Het
Cfap53	T	C	18: 74,283,223	V9A	possibly damaging	Het
Chil3	T	C	3: 106,160,478	I124V	possibly damaging	Het
Creld2	G	A	15: 88,820,631	W103*	probably null	Het
Cyp2c67	T	C	19: 39,626,237	Y282C	probably benign	Het
D5Ertd579e	C	T	5: 36,613,449	A1201T	probably benign	Het
Dock4	A	G	12: 40,692,989	H381R	probably benign	Het
Drc1	C	T	5: 30,356,441	S447F	probably benign	Het
Fam83g	G	T	11: 61,703,458	R606L	probably benign	Het
Fmnl1	A	C	11: 103,194,692	S688R	probably benign	Het
Fryl	C	T	5: 73,122,299	V219I	probably benign	Het
Gm13101	A	T	4: 143,965,820	Y204N	probably benign	Het
Golgb1	T	A	16: 36,914,664	N1424K	probably benign	Het
Gpr39	T	C	1: 125,677,884	V183A	possibly damaging	Het
H2-T22	A	T	17: 36,040,517	Y274N	probably benign	Het
Hip1r	T	A	5: 124,000,204	M787K	probably damaging	Het
Hipk3	T	C	2: 104,439,392	E484G	probably damaging	Het
Hsh2d	T	A	8: 72,200,646	F291I	probably benign	Het
Ino80	T	C	2: 119,431,929	E692G	probably null	Het
Itgam	T	A	7: 128,081,712	V271D	probably damaging	Het
Kansl1	A	C	11: 104,335,559	I924S	probably damaging	Het
Kcnq2	A	G	2: 181,081,352	C628R	probably benign	Het
Krt78	A	C	15: 101,947,414	V654G	possibly damaging	Het
Lrit2	A	G	14: 37,071,956	T326A	probably damaging	Het
Ltk	T	C	2: 119,752,088	E710G	probably damaging	Het
Lysmd1	T	C	3: 95,134,974	L53S	probably damaging	Het
Mc4r	T	C	18: 66,859,598	Y148C	probably damaging	Het
Mfn2	G	A	4: 147,888,705	Q172*	probably null	Het
Mknk2	A	G	10: 80,668,601	L242P	possibly damaging	Het
Mrpl45	A	T	11: 97,325,747	H167L	probably benign	Het
Myc	T	C	15: 61,988,102	V208A	probably damaging	Het
Myh7b	A	G	2: 155,629,457	E1175G	probably benign	Het
Myo18a	A	T	11: 77,850,234	M1456L	probably benign	Het
Myocd	G	A	11: 65,218,658	Q96*	probably null	Het
Nckap5	T	A	1: 126,026,518	I766F	probably damaging	Het
Ndst1	T	C	18: 60,691,253	E784G	probably benign	Het
Nf1	A	T	11: 79,469,826	R1443S	possibly damaging	Het
Nhlrc3	A	G	3: 53,453,651	W228R	probably damaging	Het
Nup107	G	A	10: 117,773,320	T378I	probably damaging	Het
Olfr1033	C	T	2: 86,041,330	T5I	probably damaging	Het
Olfr1131	A	G	2: 87,628,939	T159A	probably benign	Het
Olfr293	A	T	7: 86,664,383	K240N	probably damaging	Het
Olfr524	T	A	7: 140,202,743	D9V	probably benign	Het
Olfr607	T	A	7: 103,460,273		probably null	Het
Olfr98	A	T	17: 37,263,073	M197K	probably benign	Het
Otop1	A	G	5: 38,300,458	D520G	probably benign	Het
Papln	C	T	12: 83,780,236	P712S	probably benign	Het
Pcbd2	T	A	13: 55,733,033	I34N	probably damaging	Het
Pkd1l3	T	A	8: 109,647,573	C29*	probably null	Het
Pou5f1	G	A	17: 35,510,002	V114M	probably benign	Het
Prpf4b	C	A	13: 34,884,231		probably benign	Het
Prr23a1	C	T	9: 98,842,656	P24S	probably damaging	Het
Ptch1	T	A	13: 63,545,245	M65L	probably benign	Het
Rc3h2	A	T	2: 37,399,624	I392K	possibly damaging	Het
Reck	G	T	4: 43,943,195	D916Y	probably damaging	Het
Rtf2	A	G	2: 172,445,365	D68G	probably damaging	Het
Ryr1	G	T	7: 29,090,150	T1513K	probably damaging	Het
Sacs	A	G	14: 61,173,441	D55G	possibly damaging	Het
Scn9a	A	G	2: 66,568,183	S28P	probably benign	Het
Scrn3	A	G	2: 73,329,852	M280V	probably damaging	Het
Snx29	C	T	16: 11,511,034	T559I	possibly damaging	Het
Spn	C	T	7: 127,136,241	E109K	probably damaging	Het
Sra1	C	T	18: 36,675,068	R369H	probably benign	Het
Srsf11	C	T	3: 158,019,345	A64T	probably damaging	Het
Stk17b	A	G	1: 53,776,605	S12P	probably benign	Het
Sult1d1	C	A	5: 87,559,802	G153V	probably damaging	Het
Sycp2	A	T	2: 178,350,138		probably null	Het
Tgfb3	T	C	12: 86,069,769	E165G	possibly damaging	Het
Tns2	C	A	15: 102,107,506	H160N	probably benign	Het
Ubn1	T	A	16: 5,077,224	C711*	probably null	Het
Usp13	A	T	3: 32,901,986	D469V	probably damaging	Het
Vmn1r231	A	T	17: 20,890,118	H178Q	possibly damaging	Het
Vwa1	A	G	4: 155,772,793	S183P	probably damaging	Het
Xpo7	A	G	14: 70,690,991	I424T	probably benign	Het
Zfp109	A	G	7: 24,236,616		probably null	Het

Other mutations in Hif1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00979:Hif1a	APN	12	73942010	missense	probably damaging	1.00
IGL01396:Hif1a	APN	12	73940533	missense	probably benign	0.00
IGL02230:Hif1a	APN	12	73932450	missense	probably damaging	1.00
IGL02561:Hif1a	APN	12	73942206	missense	possibly damaging	0.52
IGL02698:Hif1a	APN	12	73930771	critical splice donor site	probably null
IGL03027:Hif1a	APN	12	73940477	missense	probably benign	0.03
lightweight	UTSW	12	73941800	missense	probably damaging	1.00
R0597:Hif1a	UTSW	12	73942275	missense	probably benign	0.00
R0614:Hif1a	UTSW	12	73945631	missense	probably damaging	1.00
R0678:Hif1a	UTSW	12	73944191	splice site	probably null
R0967:Hif1a	UTSW	12	73937670	missense	possibly damaging	0.91
R1351:Hif1a	UTSW	12	73940461	missense	probably benign	0.00
R1387:Hif1a	UTSW	12	73942292	missense	possibly damaging	0.95
R1858:Hif1a	UTSW	12	73944155	missense	probably benign
R2194:Hif1a	UTSW	12	73930747	missense	probably damaging	0.98
R4825:Hif1a	UTSW	12	73932401	missense	probably damaging	1.00
R4924:Hif1a	UTSW	12	73939557	missense	probably damaging	1.00
R5386:Hif1a	UTSW	12	73944093	missense	probably benign	0.02
R5594:Hif1a	UTSW	12	73937792	nonsense	probably null
R5722:Hif1a	UTSW	12	73941759	missense	probably benign	0.00
R5818:Hif1a	UTSW	12	73939564	missense	possibly damaging	0.64
R5831:Hif1a	UTSW	12	73942144	missense	probably benign
R6026:Hif1a	UTSW	12	73932281	missense	probably damaging	1.00
R6059:Hif1a	UTSW	12	73941800	missense	probably damaging	1.00
R6084:Hif1a	UTSW	12	73941842	missense	probably damaging	0.99
R6818:Hif1a	UTSW	12	73945563	nonsense	probably null
R6878:Hif1a	UTSW	12	73928281	missense	possibly damaging	0.49
R8028:Hif1a	UTSW	12	73942027	missense	probably benign	0.27
R8286:Hif1a	UTSW	12	73945248	intron	probably benign
R8322:Hif1a	UTSW	12	73939599	missense	probably benign
R8414:Hif1a	UTSW	12	73937654	missense	probably benign	0.00
R8729:Hif1a	UTSW	12	73944128	missense	probably damaging	1.00
R9030:Hif1a	UTSW	12	73936236	missense	probably damaging	1.00
R9087:Hif1a	UTSW	12	73942325	missense	probably benign	0.01
R9093:Hif1a	UTSW	12	73932337	missense	probably benign	0.12
R9300:Hif1a	UTSW	12	73940528	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- GGGCTTCTCTATCAGCTTAAACTGTC -3'
(R):5'- GGTTGGGGTATAAATCATAATCCAG -3'

Sequencing Primer
(F):5'- CCTGGTCTACATAGGGAGTTCAGAAC -3'
(R):5'- GGCTTTGAACTCATGGAGATCTACC -3'

Posted On

2014-09-18