Mutagenetix > Incidental Mutations

Incidental Mutation 'R6084:Hif1a'

482416

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

044243-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R6084 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

73901375-73947530 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 73941842 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Cysteine at position 537 (F537C)

Ref Sequence

ENSEMBL: ENSMUSP00000106088 (fasta)

Gene Model

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

AlphaFold

Q61221

Predicted Effect

possibly damaging
Transcript: ENSMUST00000021530
AA Change: F563C

PolyPhen 2 Score 0.910 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: F563C

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: F537C

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: F537C

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

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.8%

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arap2	T	C	5: 62,670,954	D958G	possibly damaging	Het
Bag4	T	C	8: 25,771,231	T161A	probably benign	Het
Bora	A	T	14: 99,062,294	Q234L	possibly damaging	Het
Cacna2d2	T	C	9: 107,497,521		probably null	Het
Cass4	G	T	2: 172,426,912	A307S	probably benign	Het
Cbln4	A	T	2: 172,042,096	V68E	probably damaging	Het
Cc2d2a	T	A	5: 43,668,673	N2K	probably benign	Het
Ccnf	T	A	17: 24,231,837	D389V	probably damaging	Het
Cdipt	T	C	7: 126,979,601	S161P	probably benign	Het
Ceacam19	T	C	7: 19,882,887	I161V	probably benign	Het
Cfap65	A	G	1: 74,920,405	I862T	probably damaging	Het
Cfi	T	A	3: 129,858,370	L230Q	probably benign	Het
Chac2	G	A	11: 30,986,159	R30W	probably damaging	Het
Cmc2	G	A	8: 116,889,827		probably benign	Het
Col1a2	A	T	6: 4,505,840	M1L	probably benign	Het
Cox8a	C	A	19: 7,217,418	R32L	possibly damaging	Het
Cubn	T	A	2: 13,430,897	N1083Y	probably damaging	Het
D430042O09Rik	G	A	7: 125,814,865	G394R	probably benign	Het
D630003M21Rik	T	C	2: 158,217,584	D132G	probably damaging	Het
Dedd2	G	A	7: 25,211,290	P154S	probably benign	Het
Dnaaf3	T	C	7: 4,524,213	D358G	probably benign	Het
Dysf	T	A	6: 84,019,604	F29L	probably damaging	Het
Dysf	T	C	6: 84,112,119	L888P	probably damaging	Het
Ebf4	A	G	2: 130,309,723	D277G	probably damaging	Het
Ecm2	T	A	13: 49,515,094	L91*	probably null	Het
Foxs1	T	C	2: 152,932,842	D97G	possibly damaging	Het
Frs2	A	C	10: 117,076,809		probably null	Het
Gm6768	A	G	12: 119,261,651		noncoding transcript	Het
Grp	A	T	18: 65,879,937	D58V	probably damaging	Het
Icam4	G	A	9: 21,029,539	S29N	probably benign	Het
Itfg1	T	C	8: 85,726,170	E523G	probably benign	Het
Jph2	T	C	2: 163,375,680	K359E	probably damaging	Het
Kcnq2	A	T	2: 181,087,656	V490E	possibly damaging	Het
Klhl18	C	T	9: 110,428,727	M548I	possibly damaging	Het
Lpin3	A	G	2: 160,895,801	Y197C	probably benign	Het
Lrp1	T	C	10: 127,560,553	N2381D	probably benign	Het
Man1a	A	T	10: 53,919,211	W649R	probably damaging	Het
Map4	T	C	9: 110,064,292	L542P	probably damaging	Het
Mboat2	A	T	12: 24,878,285	H52L	probably damaging	Het
Mok	C	G	12: 110,814,946	S91T	probably benign	Het
Mtmr11	G	T	3: 96,168,084	R360L	probably damaging	Het
Myt1l	G	A	12: 29,832,332	G509R	unknown	Het
Olfr1288	A	T	2: 111,479,389	N202Y	probably damaging	Het
Olfr341	A	G	2: 36,479,512	V206A	probably benign	Het
Olfr544	T	C	7: 102,484,389	T244A	probably damaging	Het
Olfr67	C	T	7: 103,787,955	M107I	probably benign	Het
Olfr836	A	G	9: 19,121,327	D121G	probably damaging	Het
Olfr867	A	T	9: 20,054,883	H75Q	possibly damaging	Het
Padi3	G	T	4: 140,795,843	T292N	probably damaging	Het
Pard6g	A	C	18: 80,117,205	T178P	possibly damaging	Het
Pkd1l2	A	T	8: 117,013,987	Y2124N	probably damaging	Het
Plxdc1	G	A	11: 97,928,463	T398I	probably damaging	Het
Prickle2	A	T	6: 92,416,848	C225*	probably null	Het
Prmt2	G	A	10: 76,210,444	T317I	probably benign	Het
Psg22	T	G	7: 18,719,780	N172K	probably benign	Het
Ptpn9	C	T	9: 57,033,163	R196*	probably null	Het
Rap1b	C	T	10: 117,824,611	V14I	probably damaging	Het
Rapgef4	T	A	2: 72,196,278		probably null	Het
Rlf	A	T	4: 121,149,215	M856K	possibly damaging	Het
Rnf149	A	G	1: 39,577,174	L34P	probably benign	Het
Rock1	T	C	18: 10,101,007	E636G	probably benign	Het
Rsad2	A	T	12: 26,454,123	Y136N	probably damaging	Het
Ryr3	T	C	2: 112,908,493	H563R	probably damaging	Het
Slc18b1	A	G	10: 23,804,212	M102V	probably benign	Het
Slc34a2	T	A	5: 53,067,647	C377S	possibly damaging	Het
Slco1c1	T	C	6: 141,546,770	V293A	probably benign	Het
Spidr	A	T	16: 16,140,024	S80T	possibly damaging	Het
Syne1	C	T	10: 5,348,994	E1031K	probably damaging	Het
Synj2	G	A	17: 6,017,614	V121I	probably damaging	Het
Synj2	A	T	17: 6,038,098	T1430S	probably damaging	Het
Tecpr2	G	T	12: 110,929,109	K343N	probably damaging	Het
Tmem132d	T	A	5: 127,784,100	I986F	probably benign	Het
Trib1	G	A	15: 59,654,475	R298H	probably damaging	Het
Ttll10	T	A	4: 156,045,357	D283V	probably benign	Het
Ttn	T	A	2: 76,814,779	K673*	probably null	Het
Ubqlnl	T	A	7: 104,148,698	M531L	probably benign	Het
Vmn2r120	A	T	17: 57,525,721	W153R	probably benign	Het
Vmn2r2	A	C	3: 64,117,046	S705A	probably benign	Het
Vmn2r32	T	A	7: 7,464,210	D773V	probably benign	Het
Vmn2r54	T	A	7: 12,632,278	Q243L	probably damaging	Het
Wdr24	C	A	17: 25,824,530	R109S	probably damaging	Het
Zfp113	T	C	5: 138,145,668	M107V	probably benign	Het
Zfp426	G	T	9: 20,470,627	Q341K	possibly damaging	Het
Zfp616	A	T	11: 74,083,846	K314*	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
R2105:Hif1a	UTSW	12	73937745	missense	probably damaging	1.00
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
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'- GACAACATTTGTGGCTGGTC -3'
(R):5'- AACTGGAAATCATCATCCATTGGG -3'

Posted On

2017-07-14