Mutagenetix > Incidental Mutation

Incidental Mutation 'R4825:Hif1a'

371447

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

042441-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4825 (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 73932401 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 233 (I233N)

Ref Sequence

ENSEMBL: ENSMUSP00000021530 (fasta)

Gene Model

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

AlphaFold

Q61221

Predicted Effect

probably damaging
Transcript: ENSMUST00000021530
AA Change: I233N

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

SMART Domains

Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: I233N

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

possibly damaging
Transcript: ENSMUST00000110461
AA Change: I221N

PolyPhen 2 Score 0.669 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: I221N

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

possibly damaging
Transcript: ENSMUST00000110464
AA Change: I233N

PolyPhen 2 Score 0.825 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000106091
Gene: ENSMUSG00000021109
AA Change: I233N

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: ENSMUST00000149740

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000221427

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.8%
20x: 93.8%

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: 130 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700012B07Rik	C	A	11: 109,791,672	L229F	probably benign	Het
A930002H24Rik	A	C	17: 63,863,608	S62A	unknown	Het
Abca12	T	A	1: 71,302,685	Q1039L	possibly damaging	Het
Adgrg5	T	A	8: 94,941,734	F476I	possibly damaging	Het
AI314180	G	A	4: 58,850,911	L421F	probably damaging	Het
Alms1	A	G	6: 85,678,245	K2789E	probably damaging	Het
Arrdc2	G	A	8: 70,839,277		probably null	Het
Atp2b1	T	A	10: 99,009,564	I743K	probably damaging	Het
Atp6v1c2	C	T	12: 17,289,060	G230D	probably benign	Het
AU040320	G	A	4: 126,791,793	C54Y	probably damaging	Het
BC024139	C	T	15: 76,120,317	V680I	possibly damaging	Het
Bckdhb	A	G	9: 83,988,905	D156G	probably damaging	Het
Canx	T	A	11: 50,308,809	D143V	probably benign	Het
Ccdc180	T	A	4: 45,912,794	V591E	possibly damaging	Het
Ccno	T	C	13: 112,988,099	S68P	probably benign	Het
Cdc45	C	T	16: 18,784,863	E527K	probably damaging	Het
Cep290	T	A	10: 100,488,348	D14E	probably damaging	Het
Cgnl1	A	G	9: 71,630,524	V1238A	probably benign	Het
Ciz1	C	T	2: 32,371,741	A455V	probably damaging	Het
Coro2b	T	A	9: 62,454,623	Y86F	probably benign	Het
Csf2ra	C	T	19: 61,226,552	R158Q	probably benign	Het
Cubn	A	T	2: 13,325,225	I2615N	probably damaging	Het
Dhx8	C	T	11: 101,738,170	R129*	probably null	Het
Disc1	T	A	8: 125,135,302	M471K	possibly damaging	Het
Dmxl2	G	T	9: 54,404,041	L1799I	probably benign	Het
Dnah2	A	G	11: 69,423,205	S4108P	probably damaging	Het
Ehmt2	C	G	17: 34,906,964	P211R	probably benign	Het
Eif4g3	A	G	4: 138,194,081	D1557G	probably benign	Het
Epha5	T	C	5: 84,233,840	D384G	probably damaging	Het
Etl4	A	G	2: 20,806,927	I1274V	probably damaging	Het
Fam160a1	G	A	3: 85,673,432	P489S	possibly damaging	Het
Fip1l1	G	A	5: 74,588,205		probably null	Het
Fubp1	T	C	3: 152,217,890		probably null	Het
Glul	T	C	1: 153,903,044	V33A	probably benign	Het
Gm4846	A	G	1: 166,491,668	F167S	probably damaging	Het
Heatr6	T	A	11: 83,758,322	L168M	probably damaging	Het
Hivep2	T	A	10: 14,131,319	H1220Q	possibly damaging	Het
Igkv8-21	T	C	6: 70,315,426	I9M	probably benign	Het
Izumo1	T	A	7: 45,624,987	C62*	probably null	Het
Jakmip3	G	A	7: 139,026,766	E424K	probably damaging	Het
Klhl2	A	G	8: 64,752,813	V358A	probably damaging	Het
Klk10	C	G	7: 43,783,598	D139E	probably damaging	Het
Klk14	T	C	7: 43,692,076	C51R	probably damaging	Het
Klk5	T	G	7: 43,845,390	I99S	probably damaging	Het
L3hypdh	T	C	12: 72,077,393	T258A	probably benign	Het
Lrp5	A	G	19: 3,614,292	Y812H	probably damaging	Het
Lrrc40	T	A	3: 158,061,330	L474*	probably null	Het
Mkks	A	T	2: 136,880,655	M194K	probably benign	Het
Mmp20	A	G	9: 7,654,120	D347G	probably damaging	Het
Mmp27	A	G	9: 7,581,194	E460G	probably damaging	Het
Mms22l	T	C	4: 24,536,226	F605S	probably damaging	Het
Mpzl3	A	G	9: 45,068,329	S193G	probably benign	Het
Muc4	A	T	16: 32,751,747	T542S	probably benign	Het
Muc5b	T	C	7: 141,868,465	L4446P	possibly damaging	Het
Mxi1	C	A	19: 53,370,338	S131*	probably null	Het
Nanog	G	T	6: 122,713,340	A210S	probably benign	Het
Nrcam	C	T	12: 44,575,986	Q988*	probably null	Het
Nsg1	C	A	5: 38,159,047		probably benign	Het
Ogfod3	G	A	11: 121,195,201	A189V	probably benign	Het
Olfr1121	T	A	2: 87,372,088	C185*	probably null	Het
Olfr1228	T	C	2: 89,248,690		probably null	Het
Olfr1240	A	G	2: 89,439,865	V138A	probably benign	Het
Olfr1260	G	A	2: 89,978,153	C125Y	probably damaging	Het
Olfr1465	A	T	19: 13,314,320		probably null	Het
Olfr548-ps1	T	A	7: 102,542,380	V148E	possibly damaging	Het
Olfr58	T	G	9: 19,783,576	S148A	possibly damaging	Het
Olfr632	T	C	7: 103,937,503	V41A	probably benign	Het
Olfr920	A	T	9: 38,756,407	T240S	probably damaging	Het
Olfr980	A	T	9: 40,006,742	M69K	possibly damaging	Het
Orc3	A	T	4: 34,571,774	M665K	possibly damaging	Het
Pabpc1	A	G	15: 36,597,011	S591P	probably damaging	Het
Parp6	T	A	9: 59,624,362		probably null	Het
Pcdh1	T	C	18: 38,189,859	M974V	possibly damaging	Het
Pcdhb22	T	A	18: 37,520,660	V727E	possibly damaging	Het
Pex5l	T	C	3: 32,992,985	E272G	probably damaging	Het
Pglyrp2	G	T	17: 32,418,261	N264K	probably benign	Het
Phxr4	T	A	9: 13,431,586		probably benign	Het
Piezo2	A	G	18: 63,144,954	F293S	probably damaging	Het
Pkhd1	T	C	1: 20,537,401	D1077G	probably damaging	Het
Plekhs1	A	G	19: 56,473,268		probably null	Het
Prex1	G	T	2: 166,585,857	C788*	probably null	Het
Prrt3	A	T	6: 113,498,138	M41K	probably benign	Het
Ptgir	T	C	7: 16,908,843	V326A	probably damaging	Het
Ptprg	T	A	14: 12,220,654	D455E	probably damaging	Het
Ptpru	T	A	4: 131,799,603	Q686L	probably benign	Het
Pxdc1	G	T	13: 34,630,360	T190K	probably benign	Het
Rap1b	A	T	10: 117,818,582	C118S	probably benign	Het
Rapgef2	T	C	3: 79,083,227	M915V	probably benign	Het
Rnd2	C	T	11: 101,468,999	L57F	probably damaging	Het
Rpe65	C	T	3: 159,624,681	A495V	probably benign	Het
Samd15	A	G	12: 87,200,834	T98A	possibly damaging	Het
Sdk1	T	G	5: 141,582,294	D82E	probably benign	Het
Slc26a7	T	C	4: 14,546,309	D340G	probably benign	Het
Slc6a15	T	A	10: 103,418,060	M619K	probably benign	Het
Slc7a4	C	A	16: 17,574,521	D350Y	probably damaging	Het
Slk	T	G	19: 47,619,956	N449K	probably benign	Het
Spta1	A	T	1: 174,244,042		probably null	Het
Sptbn5	A	T	2: 120,055,893		probably benign	Het
Srd5a2	A	T	17: 74,047,805	V8D	probably benign	Het
Srgap3	G	A	6: 112,727,310	A906V	probably benign	Het
Stab2	A	T	10: 86,947,147	M679K	probably benign	Het
Stk3	T	C	15: 34,999,908	I291V	probably benign	Het
Supt6	T	A	11: 78,208,134	Q1637L	possibly damaging	Het
Svil	T	C	18: 5,114,564	F2047S	probably damaging	Het
Swsap1	A	G	9: 21,955,988	E76G	probably benign	Het
Syndig1	G	T	2: 149,899,553	G20C	probably damaging	Het
Synj2bp	A	T	12: 81,502,152	N104K	probably damaging	Het
Synpo2	T	A	3: 123,114,419	D416V	probably damaging	Het
Tacc3	G	T	5: 33,672,013	C620F	probably damaging	Het
Tanc1	A	G	2: 59,699,422	E19G	probably damaging	Het
Tarsl2	C	T	7: 65,647,554	A139V	probably benign	Het
Tbc1d22a	T	A	15: 86,351,734	C365S	probably damaging	Het
Tdpoz2	T	C	3: 93,652,074	H197R	possibly damaging	Het
Tha1	A	T	11: 117,869,379	N300K	probably damaging	Het
Tm6sf1	T	A	7: 81,865,260	F70L	probably damaging	Het
Tmem132b	T	A	5: 125,783,433	S581T	probably benign	Het
Tmem206	A	T	1: 191,340,843	I154F	probably damaging	Het
Tnfsf13	G	T	11: 69,685,249	S4*	probably null	Het
Tonsl	G	A	15: 76,633,248	S757L	probably benign	Het
Trem2	G	T	17: 48,351,691	R161S	possibly damaging	Het
Trpm2	A	T	10: 77,941,173	V430E	probably damaging	Het
Ttc14	T	A	3: 33,801,369	D154E	possibly damaging	Het
Ugt2b37	T	C	5: 87,250,639	M313V	possibly damaging	Het
Uhrf1bp1	G	A	17: 27,877,394	A107T	probably damaging	Het
Vmn2r24	A	G	6: 123,815,780	I689V	probably benign	Het
Wdr76	A	G	2: 121,542,494	T601A	probably benign	Het
Xirp1	T	C	9: 120,017,003	D938G	possibly damaging	Het
Zfp608	A	T	18: 54,897,969	D966E	probably benign	Het
Zfp957	A	G	14: 79,214,356	M1T	probably null	Het
Zkscan16	A	T	4: 58,957,809	H697L	possibly damaging	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
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'- AACTGCTATGCCATCTTTCCAG -3'
(R):5'- GCATGTAGGACAAGTGATCCAC -3'

Sequencing Primer
(F):5'- ATGCCATCTTTCCAGCTCCC -3'
(R):5'- TGTAGGACAAGTGATCCACCTCTG -3'

Posted On

2016-03-01