Incidental Mutation 'R6878:Hif1a'
ID 536528
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 044974-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6878 (G1)
Quality Score 225.009
Status Validated
Chromosome 12
Chromosomal Location 73948149-73994304 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 73975055 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Threonine at position 147 (M147T)
Ref Sequence ENSEMBL: ENSMUSP00000106091 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021530] [ENSMUST00000110461] [ENSMUST00000110464]
AlphaFold Q61221
Predicted Effect possibly damaging
Transcript: ENSMUST00000021530
AA Change: M147T

PolyPhen 2 Score 0.486 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: M147T

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 possibly damaging
Transcript: ENSMUST00000110461
AA Change: M135T

PolyPhen 2 Score 0.456 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: M135T

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 possibly damaging
Transcript: ENSMUST00000110464
AA Change: M147T

PolyPhen 2 Score 0.486 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000106091
Gene: ENSMUSG00000021109
AA Change: M147T

DomainStartEndE-ValueType
HLH 23 78 1.29e-8 SMART
PAS 87 153 1.05e-9 SMART
Meta Mutation Damage Score 0.1111 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.3%
  • 20x: 97.7%
Validation Efficiency 98% (44/45)
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: 48 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgrv1 A T 13: 81,581,613 (GRCm39) N4810K probably benign Het
Arhgap26 A T 18: 39,360,465 (GRCm39) I397F probably damaging Het
Arhgap35 A G 7: 16,299,038 (GRCm39) V9A probably benign Het
Asl A G 5: 130,053,133 (GRCm39) probably null Het
Atg2a T A 19: 6,300,208 (GRCm39) L672Q probably damaging Het
B4galt1 T C 4: 40,809,694 (GRCm39) D316G probably damaging Het
Bpifb2 A G 2: 153,717,832 (GRCm39) probably benign Het
Ccl1 T C 11: 82,070,519 (GRCm39) I18V probably benign Het
Cd47 A G 16: 49,731,232 (GRCm39) E278G possibly damaging Het
Cilp G A 9: 65,187,129 (GRCm39) G1075S probably damaging Het
Eml2 T C 7: 18,934,537 (GRCm39) V604A probably benign Het
Fancm A T 12: 65,163,197 (GRCm39) R1454* probably null Het
Gm4302 TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA 10: 100,177,361 (GRCm39) probably benign Het
Gm4302 GCA GCACCA 10: 100,177,377 (GRCm39) probably benign Het
Gm4302 CAG CAGAAG 10: 100,177,369 (GRCm39) probably benign Het
Hps5 C G 7: 46,433,058 (GRCm39) A221P probably damaging Het
Lrrc49 A G 9: 60,587,431 (GRCm39) S67P probably damaging Het
Madd T A 2: 91,000,202 (GRCm39) N568I probably damaging Het
Meikin T C 11: 54,302,712 (GRCm39) S375P possibly damaging Het
Mfsd6 G T 1: 52,747,912 (GRCm39) Q318K probably damaging Het
Mis18a A T 16: 90,518,644 (GRCm39) I106N probably damaging Het
Myl2 T C 5: 122,243,140 (GRCm39) I148T probably benign Het
Myrf T C 19: 10,193,842 (GRCm39) Q730R possibly damaging Het
Nf1 T C 11: 79,325,708 (GRCm39) L560P probably damaging Het
Npat A G 9: 53,467,899 (GRCm39) T285A probably benign Het
Ntrk3 T A 7: 77,954,120 (GRCm39) D547V probably benign Het
Obox2 G T 7: 15,131,245 (GRCm39) S117I probably benign Het
Or8k32 A G 2: 86,369,109 (GRCm39) L48P probably damaging Het
Parva T A 7: 112,175,656 (GRCm39) N226K possibly damaging Het
Pcdha3 T A 18: 37,080,416 (GRCm39) L386* probably null Het
Ppip5k1 A G 2: 121,142,417 (GRCm39) F1323S probably benign Het
Prkdc T C 16: 15,594,936 (GRCm39) V2771A probably benign Het
Prl7c1 T C 13: 27,962,827 (GRCm39) T59A possibly damaging Het
Rab15 T C 12: 76,851,257 (GRCm39) T20A probably benign Het
Rp1l1 A G 14: 64,269,301 (GRCm39) E1629G probably benign Het
Rpap1 A T 2: 119,608,657 (GRCm39) L235Q probably damaging Het
Sema3a A T 5: 13,505,511 (GRCm39) I91F possibly damaging Het
Snx6 T C 12: 54,810,386 (GRCm39) probably null Het
Sorbs1 G C 19: 40,365,244 (GRCm39) R180G probably benign Het
Speer4f2 T G 5: 17,580,765 (GRCm39) M114R probably damaging Het
Syne1 T C 10: 5,370,388 (GRCm39) D264G possibly damaging Het
Tbl1xr1 T G 3: 22,257,368 (GRCm39) N410K possibly damaging Het
Tmed7 A T 18: 46,726,532 (GRCm39) D74E probably damaging Het
Upk3b T C 5: 136,068,001 (GRCm39) V64A probably benign Het
Vmn2r29 A G 7: 7,244,863 (GRCm39) V337A probably benign Het
Yy1 C G 12: 108,780,682 (GRCm39) P352A probably damaging Het
Zfp1005 C T 2: 150,108,406 (GRCm39) L56F possibly damaging Het
Zfp873 T C 10: 81,896,529 (GRCm39) I457T probably benign 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
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'- CGTGAACAAATACATGGGGTTAAC -3'
(R):5'- TGAACCCAAACTGTCACTGTG -3'

Sequencing Primer
(F):5'- GGGTTAACTCAGGTAAAGTCCCC -3'
(R):5'- GAACCCAAACTGTCACTGTGTATTC -3'
Posted On 2018-10-18