Incidental Mutation 'R1351:Hif1a'
ID 156664
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 039416-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1351 (G1)
Quality Score 225
Status Validated
Chromosome 12
Chromosomal Location 73948149-73994304 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 73987235 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 443 (S443P)
Ref Sequence ENSEMBL: ENSMUSP00000106088 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021530] [ENSMUST00000110461]
AlphaFold Q61221
Predicted Effect probably benign
Transcript: ENSMUST00000021530
AA Change: S455P

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: S455P

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: S443P

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: S443P

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 noncoding transcript
Transcript: ENSMUST00000125308
Predicted Effect noncoding transcript
Transcript: ENSMUST00000157041
Predicted Effect noncoding transcript
Transcript: ENSMUST00000221427
Predicted Effect probably benign
Transcript: ENSMUST00000221833
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.1%
  • 20x: 95.0%
Validation Efficiency 100% (51/51)
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
Arhgef26 A G 3: 62,288,262 (GRCm39) E444G probably damaging Het
Astl G A 2: 127,189,105 (GRCm39) V144M possibly damaging Het
AW146154 A T 7: 41,129,878 (GRCm39) C413S probably damaging Het
Bicdl2 G A 17: 23,886,519 (GRCm39) probably benign Het
Cacna1h G T 17: 25,610,925 (GRCm39) S624R probably benign Het
Car9 G T 4: 43,512,439 (GRCm39) probably null Het
Cep126 C T 9: 8,100,087 (GRCm39) E816K probably damaging Het
Cyp2j13 T C 4: 95,945,155 (GRCm39) K291R probably benign Het
Defb26 A T 2: 152,349,737 (GRCm39) M181K unknown Het
Dicer1 G A 12: 104,695,401 (GRCm39) R177C probably damaging Het
Eif4g2 A G 7: 110,673,287 (GRCm39) Y831H probably damaging Het
Ermap C T 4: 119,038,558 (GRCm39) probably null Het
Fcamr C T 1: 130,740,757 (GRCm39) T392I possibly damaging Het
Fgf3 T C 7: 144,394,517 (GRCm39) probably benign Het
Gpr162 T C 6: 124,838,161 (GRCm39) Y163C probably damaging Het
Gprc5d T C 6: 135,093,230 (GRCm39) R226G possibly damaging Het
Hapln3 A C 7: 78,771,708 (GRCm39) S60R probably damaging Het
Irf2bpl A G 12: 86,929,398 (GRCm39) M425T probably benign Het
Lrrc39 G T 3: 116,359,469 (GRCm39) A5S possibly damaging Het
Mbtps1 A G 8: 120,244,901 (GRCm39) L850S possibly damaging Het
Mios T A 6: 8,228,120 (GRCm39) M679K possibly damaging Het
Mocos T C 18: 24,793,107 (GRCm39) F68S probably damaging Het
Nuf2 T C 1: 169,338,118 (GRCm39) probably benign Het
Or51k1 A G 7: 103,661,523 (GRCm39) Y129H possibly damaging Het
Orc1 T A 4: 108,452,564 (GRCm39) D146E probably benign Het
Pcdhb22 T C 18: 37,651,627 (GRCm39) F32L probably benign Het
Pde4d G T 13: 110,087,809 (GRCm39) E562D possibly damaging Het
Pgk2 T C 17: 40,518,691 (GRCm39) K246E probably damaging Het
Plekhh2 A T 17: 84,884,574 (GRCm39) probably benign Het
Pou3f2 A T 4: 22,487,162 (GRCm39) C324S probably damaging Het
Prkdc C T 16: 15,485,564 (GRCm39) L464F possibly damaging Het
Prrc2a T C 17: 35,376,863 (GRCm39) H749R possibly damaging Het
Rad18 T C 6: 112,597,863 (GRCm39) N218S possibly damaging Het
Rbm11 T C 16: 75,393,531 (GRCm39) Y76H possibly damaging Het
Rif1 T G 2: 52,001,567 (GRCm39) Y1674D possibly damaging Het
Rrp1b A G 17: 32,275,611 (GRCm39) H386R possibly damaging Het
Sacs T C 14: 61,440,210 (GRCm39) V752A probably benign Het
Sema3c A G 5: 17,883,334 (GRCm39) D314G possibly damaging Het
Spata2l G A 8: 123,960,072 (GRCm39) R406C probably damaging Het
Tacc2 C T 7: 130,264,733 (GRCm39) probably benign Het
Tent4b C A 8: 88,927,002 (GRCm39) Y137* probably null Het
Trpc4 A G 3: 54,102,423 (GRCm39) E107G probably damaging Het
Vmn2r70 A G 7: 85,214,262 (GRCm39) S297P probably damaging Het
Xdh A G 17: 74,230,073 (GRCm39) I286T probably benign Het
Zfp608 T C 18: 55,031,463 (GRCm39) T826A probably benign Het
Zfp646 T A 7: 127,482,683 (GRCm39) V1620E probably benign Het
Zfyve28 T G 5: 34,389,549 (GRCm39) D217A probably damaging Het
Zmym6 G A 4: 127,016,798 (GRCm39) G768R 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
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
R9300:Hif1a UTSW 12 73,987,302 (GRCm39) missense probably benign 0.04
Predicted Primers PCR Primer
(F):5'- CACCTCACTGCACCATTCAGTAGAG -3'
(R):5'- AGTGCTTCCATCAGAAGGACTTGC -3'

Sequencing Primer
(F):5'- CTCCTATCAGTGGTGGACTATAACAG -3'
(R):5'- ACTTGCTGGCTGATCTTGAATC -3'
Posted On 2014-02-11