Incidental Mutation 'R9300:Hif1a'
ID 704885
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
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9300 (G1)
Quality Score 225.009
Status Not validated
Chromosome 12
Chromosomal Location 73948149-73994304 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 73987302 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Serine at position 477 (L477S)
Ref Sequence ENSEMBL: ENSMUSP00000021530 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021530] [ENSMUST00000110461]
AlphaFold Q61221
Predicted Effect probably benign
Transcript: ENSMUST00000021530
AA Change: L477S

PolyPhen 2 Score 0.041 (Sensitivity: 0.94; Specificity: 0.83)
SMART Domains Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: L477S

DomainStartEndE-ValueType
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: L465S

PolyPhen 2 Score 0.097 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: L465S

DomainStartEndE-ValueType
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: ENSMUST00000221833
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
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: 88 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb1b G A 5: 8,875,614 (GRCm39) V596I probably benign Het
Acad8 A T 9: 26,888,928 (GRCm39) H371Q probably damaging Het
Actn3 G T 19: 4,921,656 (GRCm39) R175S probably benign Het
Adamts9 G T 6: 92,864,371 (GRCm39) D780E probably benign Het
AK157302 C A 13: 21,679,537 (GRCm39) T21K probably benign Het
Ank3 A T 10: 69,706,872 (GRCm39) H329L unknown Het
Ankrd36 A G 11: 5,519,979 (GRCm39) H18R possibly damaging Het
Anks1b T A 10: 90,412,966 (GRCm39) V38D possibly damaging Het
Apbb2 A T 5: 66,470,677 (GRCm39) L520H probably damaging Het
Arid1b C A 17: 5,293,274 (GRCm39) P731T probably damaging Het
Atp1a4 A G 1: 172,067,398 (GRCm39) F578S probably damaging Het
Atp6v0a2 A T 5: 124,789,312 (GRCm39) I360F probably damaging Het
Bcas3 A T 11: 85,448,184 (GRCm39) I600F probably damaging Het
C1qtnf7 T G 5: 43,766,441 (GRCm39) C20W possibly damaging Het
Cadm1 A T 9: 47,708,821 (GRCm39) K184* probably null Het
Ccdc138 A T 10: 58,343,448 (GRCm39) H101L probably benign Het
Cep120 T A 18: 53,852,369 (GRCm39) N503I probably damaging Het
Chil4 T C 3: 106,109,874 (GRCm39) T380A probably benign Het
Clip2 A G 5: 134,526,942 (GRCm39) probably null Het
Cyp3a11 G A 5: 145,799,164 (GRCm39) P341L possibly damaging Het
Cyp3a41a G C 5: 145,656,906 (GRCm39) probably benign Het
Dcaf1 A G 9: 106,725,042 (GRCm39) I509M possibly damaging Het
Dcaf13 T C 15: 39,010,102 (GRCm39) S429P probably damaging Het
Eln A G 5: 134,758,220 (GRCm39) V151A unknown Het
Endou T G 15: 97,610,954 (GRCm39) M377L probably benign Het
Etfa A G 9: 55,396,152 (GRCm39) I138T probably damaging Het
Fbxw10 T A 11: 62,768,109 (GRCm39) S982T probably benign Het
Gm9602 A T 14: 15,933,435 (GRCm39) R47* probably null Het
Hectd4 G A 5: 121,486,952 (GRCm39) V3316I probably benign Het
Icam5 G C 9: 20,946,846 (GRCm39) G458A probably benign Het
Itm2b A T 14: 73,603,896 (GRCm39) D106E probably benign Het
Kdm4d G A 9: 14,375,336 (GRCm39) T174M probably damaging Het
Kif16b G T 2: 142,541,207 (GRCm39) D1364E probably benign Het
Lbhd1 G A 19: 8,861,550 (GRCm39) V61M probably damaging Het
Lclat1 T A 17: 73,546,919 (GRCm39) S279T probably benign Het
Lhx4 G A 1: 155,580,956 (GRCm39) L190F probably damaging Het
Lima1 C T 15: 99,704,320 (GRCm39) S283N probably benign Het
Magi1 C A 6: 93,724,209 (GRCm39) D496Y probably damaging Het
Map1a T C 2: 121,133,446 (GRCm39) S1421P probably damaging Het
Map3k20 C T 2: 72,202,257 (GRCm39) H163Y probably damaging Het
Mier3 T G 13: 111,822,890 (GRCm39) probably null Het
Mllt3 G A 4: 87,692,284 (GRCm39) Q560* probably null Het
Mmp25 T A 17: 23,851,728 (GRCm39) D327V probably benign Het
Nckap5 G A 1: 125,909,423 (GRCm39) Q1603* probably null Het
Nell1 G A 7: 49,712,368 (GRCm39) V63I probably benign Het
Or10al3 C T 17: 38,011,815 (GRCm39) P85S probably damaging Het
Or2ag2b A T 7: 106,418,111 (GRCm39) I274F probably benign Het
Or8a1 A C 9: 37,641,578 (GRCm39) S234A probably benign Het
Pde12 C T 14: 26,386,931 (GRCm39) E526K probably damaging Het
Pfn4 T C 12: 4,825,442 (GRCm39) V93A possibly damaging Het
Poglut2 A G 1: 44,156,362 (GRCm39) I75T possibly damaging Het
Ppp2r3d A G 9: 124,423,977 (GRCm38) S60P unknown Het
Prelp T C 1: 133,842,257 (GRCm39) H296R probably damaging Het
Prickle1 T C 15: 93,398,749 (GRCm39) E693G possibly damaging Het
Rars1 A G 11: 35,706,488 (GRCm39) L477P probably damaging Het
Rasal1 G A 5: 120,802,172 (GRCm39) R328H probably damaging Het
Rasef A G 4: 73,659,393 (GRCm39) F220S probably benign Het
Rif1 C T 2: 52,001,151 (GRCm39) S1535L probably damaging Het
Rnf17 T C 14: 56,697,495 (GRCm39) I463T possibly damaging Het
Ryr3 A T 2: 112,690,695 (GRCm39) D1138E probably benign Het
Scn9a T A 2: 66,335,236 (GRCm39) Y1251F probably benign Het
Sdk2 A G 11: 113,715,856 (GRCm39) W1568R possibly damaging Het
Senp6 A G 9: 80,049,433 (GRCm39) E1019G probably damaging Het
Shh A G 5: 28,663,461 (GRCm39) Y236H probably damaging Het
Sin3a A G 9: 57,014,744 (GRCm39) D655G probably damaging Het
Slc35a4 C T 18: 36,815,274 (GRCm39) P35S probably damaging Het
Slc35g1 T C 19: 38,384,633 (GRCm39) L24P probably benign Het
Slc39a4 G T 15: 76,498,759 (GRCm39) Q312K probably damaging Het
Slc6a5 A T 7: 49,601,175 (GRCm39) I659F probably damaging Het
Slc7a4 T C 16: 17,392,399 (GRCm39) Y345C probably benign Het
Slco6c1 G T 1: 96,993,809 (GRCm39) R645S probably benign Het
Soat1 T C 1: 156,268,923 (GRCm39) Y209C probably benign Het
Tbc1d9b T C 11: 50,054,714 (GRCm39) S953P probably benign Het
Tgm1 G A 14: 55,942,303 (GRCm39) H683Y probably benign Het
Tmem98 G A 11: 80,708,432 (GRCm39) R134Q probably damaging Het
Trpm3 A C 19: 22,955,745 (GRCm39) M1107L possibly damaging Het
Vmn1r11 G A 6: 57,114,872 (GRCm39) V179I probably benign Het
Vmn1r119 G T 7: 20,745,638 (GRCm39) T248K probably damaging Het
Vmn1r236 T A 17: 21,506,945 (GRCm39) I21N possibly damaging Het
Vmn2r24 A G 6: 123,793,030 (GRCm39) T786A possibly damaging Het
Vstm5 A T 9: 15,168,585 (GRCm39) I50F probably damaging Het
Wdr1 T C 5: 38,685,255 (GRCm39) D572G probably damaging Het
Xaf1 T C 11: 72,192,517 (GRCm39) F5S probably benign Het
Zan A T 5: 137,468,519 (GRCm39) probably null Het
Zfp697 T C 3: 98,334,979 (GRCm39) V248A possibly damaging Het
Zftraf1 C A 15: 76,530,541 (GRCm39) V260L probably benign Het
Zkscan3 T A 13: 21,577,667 (GRCm39) T249S unknown Het
Znfx1 A G 2: 166,897,860 (GRCm39) Y355H probably damaging Het
Other mutations in Hif1a
AlleleSourceChrCoordTypePredicted EffectPPH 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
R0597:Hif1a UTSW 12 73,989,049 (GRCm39) missense probably benign 0.00
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
Predicted Primers PCR Primer
(F):5'- GTCCTCTTGATTGACAAACGC -3'
(R):5'- GCCCTGGTCCAACCTAGATATG -3'

Sequencing Primer
(F):5'- GACAAACGCTTTCCTCTGCAG -3'
(R):5'- CCTGGTCCAACCTAGATATGATGAG -3'
Posted On 2022-03-25