Mutagenetix > Incidental Mutation

Incidental Mutation 'R9093:Hif1a'

691166

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 #

R9093 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

73948149-73994304 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 73979111 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 212 (Y212H)

Ref Sequence

ENSEMBL: ENSMUSP00000021530 (fasta)

Gene Model

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

AlphaFold

Q61221

Predicted Effect

probably benign
Transcript: ENSMUST00000021530
AA Change: Y212H

PolyPhen 2 Score 0.120 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000021530
Gene: ENSMUSG00000021109
AA Change: Y212H

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 benign
Transcript: ENSMUST00000110461
AA Change: Y200H

PolyPhen 2 Score 0.037 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000106088
Gene: ENSMUSG00000021109
AA Change: Y200H

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

probably benign
Transcript: ENSMUST00000110464
AA Change: Y212H

PolyPhen 2 Score 0.120 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000106091
Gene: ENSMUSG00000021109
AA Change: Y212H

Domain	Start	End	E-Value	Type
HLH	23	78	1.29e-8	SMART
PAS	87	153	1.05e-9	SMART

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

97% (76/78)

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb11	A	T	2: 69,069,513 (GRCm39)	V1294E	probably damaging	Het
Ada	C	T	2: 163,577,308 (GRCm39)	G60D	probably benign	Het
Aff3	G	T	1: 38,291,738 (GRCm39)	R390S	possibly damaging	Het
Aldh3b3	T	A	19: 4,013,959 (GRCm39)	N53K	possibly damaging	Het
Ankrd36	G	A	11: 5,589,132 (GRCm39)	M410I	probably benign	Het
Ap2b1	T	A	11: 83,215,395 (GRCm39)	I113N	probably damaging	Het
Art5	G	T	7: 101,747,396 (GRCm39)	H128N	probably benign	Het
Calhm2	A	C	19: 47,121,599 (GRCm39)	L190R	probably benign	Het
Catsperg1	G	C	7: 28,884,152 (GRCm39)	T987R	probably damaging	Het
Cdh18	A	T	15: 23,474,064 (GRCm39)	I645F	probably damaging	Het
Cenpe	C	T	3: 134,945,641 (GRCm39)	Q1052*	probably null	Het
Cfap221	G	T	1: 119,863,856 (GRCm39)	Q563K	probably damaging	Het
Cfap54	T	A	10: 92,651,770 (GRCm39)	E3093D	probably benign	Het
Chd4	A	G	6: 125,090,974 (GRCm39)	M1186V	probably benign	Het
Chst15	A	T	7: 131,870,646 (GRCm39)		probably null	Het
Clca3a2	T	C	3: 144,781,481 (GRCm39)	T688A	probably benign	Het
Cmtm1	TCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGG	TCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGGCTGGCTGGTGTCCCGGGTACTGAAGGTCCCTGG	8: 105,036,334 (GRCm39)		probably null	Het
Cul1	T	A	6: 47,495,173 (GRCm39)	N518K	probably damaging	Het
E230025N22Rik	G	T	18: 36,821,952 (GRCm39)	L247I	possibly damaging	Het
Eno4	A	T	19: 58,941,600 (GRCm39)	K174*	probably null	Het
Enpp3	G	A	10: 24,671,702 (GRCm39)	P431S	probably benign	Het
Fbh1	T	A	2: 11,764,801 (GRCm39)	Q444H	probably damaging	Het
Fbxo31	G	A	8: 122,281,136 (GRCm39)	R337C	probably damaging	Het
Fbxw14	A	G	9: 109,105,250 (GRCm39)	I305T	probably benign	Het
Fhip1b	T	A	7: 105,034,599 (GRCm39)	T408S	probably damaging	Het
Gas2	T	A	7: 51,602,969 (GRCm39)	C216S	probably damaging	Het
Gjb3	GCCAGATGCGCCCA	GCCAGATGCGCCCAGATGCGCCCA	4: 127,220,458 (GRCm39)		probably null	Het
Glp2r	T	A	11: 67,621,459 (GRCm39)	R344*	probably null	Het
Gm17430	A	G	18: 9,726,640 (GRCm39)	Y11H	probably damaging	Het
Gyg1	T	A	3: 20,176,901 (GRCm39)	D363V	probably damaging	Het
H2bc18	G	A	3: 96,177,290 (GRCm39)	A75T	probably benign	Het
Hectd4	A	G	5: 121,411,677 (GRCm39)	N451S	probably benign	Het
Hoxd11	A	T	2: 74,514,482 (GRCm39)	*337C	probably null	Het
Kif24	A	G	4: 41,428,691 (GRCm39)	F90L	probably benign	Het
Klhl20	A	T	1: 160,923,231 (GRCm39)	C497*	probably null	Het
Loxl1	C	A	9: 58,219,224 (GRCm39)	A316S	probably benign	Het
Lrig3	C	T	10: 125,845,950 (GRCm39)	P793L	possibly damaging	Het
Macc1	A	G	12: 119,410,561 (GRCm39)	D443G	probably benign	Het
Maip1	A	T	1: 57,446,311 (GRCm39)	Y127F	possibly damaging	Het
Mrm2	A	T	5: 140,314,427 (GRCm39)	F136Y	probably benign	Het
Nasp	G	T	4: 116,468,017 (GRCm39)	L323I	probably benign	Het
Ndufb8	A	T	19: 44,538,823 (GRCm39)	L166Q	probably damaging	Het
Nid2	C	T	14: 19,858,009 (GRCm39)	T1274I		Het
Nup210	T	A	6: 91,066,872 (GRCm39)	T160S	probably benign	Het
Nutm2	A	G	13: 50,628,964 (GRCm39)	K676R	probably damaging	Het
Odad1	G	A	7: 45,596,965 (GRCm39)	V431I	possibly damaging	Het
Or10a3n	T	C	7: 108,493,609 (GRCm39)	R7G	probably benign	Het
Or2a20	A	G	6: 43,194,500 (GRCm39)	T218A	probably benign	Het
Or56b1b	A	T	7: 108,164,454 (GRCm39)	C183S	probably damaging	Het
Or5ak20	T	A	2: 85,183,852 (GRCm39)	R139S	probably benign	Het
Or7g33	A	G	9: 19,448,914 (GRCm39)	V104A	probably benign	Het
Or8b9	A	T	9: 37,766,294 (GRCm39)	Y60F	probably damaging	Het
Or9m1	A	T	2: 87,733,480 (GRCm39)	I180N	probably benign	Het
Pcdhga12	C	A	18: 37,899,931 (GRCm39)	N254K	possibly damaging	Het
Pm20d1	G	T	1: 131,743,753 (GRCm39)	V473F	probably benign	Het
Pou2af2	G	A	9: 51,201,516 (GRCm39)	P180L	possibly damaging	Het
Rab11fip1	A	G	8: 27,633,355 (GRCm39)	V596A	probably damaging	Het
Rapgef6	C	T	11: 54,487,912 (GRCm39)	Q13*	probably null	Het
Rasef	T	C	4: 73,698,583 (GRCm39)	D26G	probably benign	Het
Rbfox2	A	T	15: 77,190,658 (GRCm39)	V29E	probably benign	Het
Recql4	G	A	15: 76,589,685 (GRCm39)	P787S	unknown	Het
Rnf19a	A	C	15: 36,253,450 (GRCm39)		probably benign	Het
Rnf214	A	G	9: 45,811,054 (GRCm39)	I203T	probably damaging	Het
Rnmt	A	C	18: 68,451,146 (GRCm39)	E396D	probably benign	Het
Scn4a	G	A	11: 106,210,638 (GRCm39)	S1793L	probably benign	Het
Sdcbp	G	T	4: 6,386,709 (GRCm39)		probably null	Het
Slfn3	A	G	11: 83,103,948 (GRCm39)	N273S	probably damaging	Het
Slk	A	G	19: 47,603,883 (GRCm39)	D209G		Het
Tent5b	A	G	4: 133,214,352 (GRCm39)	T408A	probably damaging	Het
Tmem135	T	A	7: 88,797,204 (GRCm39)	M351L	probably benign	Het
Tmem64	A	G	4: 15,266,391 (GRCm39)	H147R	probably benign	Het
Tnfsf4	T	C	1: 161,244,629 (GRCm39)	L106P	probably damaging	Het
Tonsl	A	T	15: 76,515,270 (GRCm39)	C1039S	probably damaging	Het
Ube4a	A	T	9: 44,864,462 (GRCm39)	F44I	possibly damaging	Het
Vmn2r40	A	G	7: 8,911,172 (GRCm39)	L707P		Het
Vmn2r87	G	A	10: 130,308,165 (GRCm39)	T691I	probably benign	Het
Wbp11	A	T	6: 136,803,044 (GRCm39)	S7T	possibly damaging	Het
Zfp386	C	A	12: 116,023,878 (GRCm39)	S532*	probably null	Het

Other mutations in Hif1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R9300:Hif1a	UTSW	12	73,987,302 (GRCm39)	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- AGCACCCTACCTTCACAATGTTG -3'
(R):5'- CATGTAGGACAAGTGATCCACC -3'

Sequencing Primer
(F):5'- ACAATGTTGTGGGGTTGTTTTG -3'
(R):5'- CTCCTCATAGCTAAGATTACAGGAGG -3'

Posted On

2021-12-30