Mutagenetix > Incidental Mutation

Incidental Mutation 'R8701:Alox5'

669063

Institutional Source

Beutler Lab

Gene Symbol

Alox5

Ensembl Gene

ENSMUSG00000025701

Gene Name

arachidonate 5-lipoxygenase

Synonyms

5LO, 5-LOX, 5LX

MMRRC Submission

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.146) question?

Stock #

R8701 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

116410077-116461178 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 116413826 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 455 (I455F)

Ref Sequence

ENSEMBL: ENSMUSP00000026795 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026795] [ENSMUST00000079012] [ENSMUST00000101032] [ENSMUST00000164547] [ENSMUST00000170186] [ENSMUST00000203193] [ENSMUST00000203722]

AlphaFold

P48999

Predicted Effect

possibly damaging
Transcript: ENSMUST00000026795
AA Change: I455F

PolyPhen 2 Score 0.466 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000026795
Gene: ENSMUSG00000025701
AA Change: I455F

Domain	Start	End	E-Value	Type
LH2	2	115	3.41e-39	SMART
Pfam:Lipoxygenase	212	662	1.5e-79	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000079012

SMART Domains

Protein: ENSMUSP00000078024
Gene: ENSMUSG00000025702

Domain	Start	End	E-Value	Type
low complexity region	47	64	N/A	INTRINSIC
RINGv	75	123	1.16e-23	SMART
transmembrane domain	151	173	N/A	INTRINSIC
transmembrane domain	188	210	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000101032

SMART Domains

Protein: ENSMUSP00000098594
Gene: ENSMUSG00000025702

Domain	Start	End	E-Value	Type
low complexity region	47	64	N/A	INTRINSIC
RINGv	75	123	1.16e-23	SMART
transmembrane domain	151	173	N/A	INTRINSIC
transmembrane domain	188	210	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000164547
AA Change: I455F

PolyPhen 2 Score 0.714 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000130780
Gene: ENSMUSG00000025701
AA Change: I455F

Domain	Start	End	E-Value	Type
LH2	2	115	3.41e-39	SMART
Pfam:Lipoxygenase	125	217	5.1e-12	PFAM
Pfam:Lipoxygenase	213	564	8.4e-133	PFAM
Pfam:Lipoxygenase	558	609	7.3e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000170186

SMART Domains

Protein: ENSMUSP00000130424
Gene: ENSMUSG00000025701

Domain	Start	End	E-Value	Type
LH2	2	115	3.41e-39	SMART
Pfam:Lipoxygenase	150	220	1.9e-13	PFAM
Pfam:Lipoxygenase	215	432	8.6e-79	PFAM
Pfam:Lipoxygenase	426	634	1e-73	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000203193

SMART Domains

Protein: ENSMUSP00000145137
Gene: ENSMUSG00000025702

Domain	Start	End	E-Value	Type
low complexity region	8	25	N/A	INTRINSIC
RINGv	36	84	2.9e-26	SMART
transmembrane domain	112	134	N/A	INTRINSIC
transmembrane domain	149	171	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000203722

SMART Domains

Protein: ENSMUSP00000145367
Gene: ENSMUSG00000025701

Domain	Start	End	E-Value	Type
LH2	2	115	2.2e-41	SMART
Pfam:Lipoxygenase	213	430	3e-35	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.8%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
PHENOTYPE: Nullizygous mice show altered inflammatory responses. One null mutation causes resistance to lethal anaphylaxis, abnormal eicosanoid production and neutrophil recruitment while another leads to increased body fat, bone density, leptin and VLDL cholesterol levels and resistance to autoimmune uveitis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 65 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931408C20Rik	A	T	1: 26,685,445	V218D	probably benign	Het
Abcc4	T	C	14: 118,599,373	I659V	probably benign	Het
Adamtsl4	T	A	3: 95,684,966	D24V	possibly damaging	Het
Agtr1b	A	T	3: 20,316,092	F117I	probably damaging	Het
Aldh3b2	A	G	19: 3,978,448	E116G	probably damaging	Het
Arnt	C	T	3: 95,493,765	S675F	possibly damaging	Het
C330027C09Rik	T	A	16: 49,007,141	Y456*	probably null	Het
Camkv	A	G	9: 107,948,041	T414A	possibly damaging	Het
Cd209c	C	T	8: 3,945,892	R6H	probably benign	Het
Cnr1	A	G	4: 33,944,739	I376V	probably benign	Het
Cyp2j12	T	A	4: 96,121,573	K183M	possibly damaging	Het
Dact3	G	T	7: 16,885,276	R232L	probably damaging	Het
Dlg5	G	A	14: 24,176,700	T378M	probably benign	Het
Dnah10	T	A	5: 124,726,847	D79E	probably benign	Het
Dsc1	A	T	18: 20,107,682	Y195*	probably null	Het
Elovl1	A	T	4: 118,430,510	M1L	probably benign	Het
Fam107a	A	G	14: 8,298,755	F124L	probably damaging	Het
Fam219a	A	G	4: 41,520,283	M155T	probably damaging	Het
Gm28308	C	G	6: 52,163,450		probably benign	Het
Gpr153	C	T	4: 152,279,101		probably benign	Het
Gtf2ird2	T	A	5: 134,216,235	I445N	probably damaging	Het
Gzmb	A	T	14: 56,260,360	V141E	probably benign	Het
Hmcn1	A	T	1: 150,755,257	M930K	probably benign	Het
Hunk	T	A	16: 90,386,610	F52Y	probably damaging	Het
Il18rap	A	G	1: 40,539,341	E304G	probably benign	Het
Klk14	A	G	7: 43,694,142	S133G	possibly damaging	Het
Man2b1	T	C	8: 85,095,153	S695P	probably damaging	Het
Mccc1	A	T	3: 35,995,784	D86E	probably benign	Het
Mcu	T	A	10: 59,467,653	I121F	probably damaging	Het
Mlxipl	T	C	5: 135,107,191	F90S	possibly damaging	Het
Muc2	A	G	7: 141,695,607	D536G	probably damaging	Het
Naa11	T	C	5: 97,391,958	S114G	possibly damaging	Het
Ncaph	T	C	2: 127,106,138	K676E	probably benign	Het
Neurl2	C	T	2: 164,833,134	D103N	probably benign	Het
Nup210l	T	C	3: 90,122,814	M278T	probably benign	Het
Olfr1192-ps1	A	G	2: 88,652,487	I112V	possibly damaging	Het
Olfr550	A	T	7: 102,578,692	M66L	possibly damaging	Het
Olfr897-ps1	A	T	9: 38,309,438	L214F	unknown	Het
Olfr967	A	T	9: 39,750,914	H176L	probably damaging	Het
Olfr981	A	G	9: 40,022,519	N42S	probably damaging	Het
Pcdh20	A	T	14: 88,468,413	Y484N	possibly damaging	Het
Pkhd1l1	A	G	15: 44,574,683	Y3598C	probably damaging	Het
Plcg2	T	A	8: 117,581,677	L336Q	probably damaging	Het
Ppp1r8	T	C	4: 132,830,642	D207G	possibly damaging	Het
Prdm13	C	T	4: 21,678,615	C625Y	probably damaging	Het
Ptcd3	T	C	6: 71,885,511	D480G	possibly damaging	Het
Rbm39	T	A	2: 156,161,587	K291M	probably damaging	Het
Repin1	G	T	6: 48,597,345	E403*	probably null	Het
Rnf220	T	C	4: 117,489,993	H74R	probably damaging	Het
Sp6	A	T	11: 97,022,264	T268S	probably damaging	Het
Sphk2	A	T	7: 45,710,825	V585E	probably damaging	Het
Syne1	G	A	10: 5,205,026	Q5638*	probably null	Het
Tas1r3	C	T	4: 155,861,046	V573I	probably benign	Het
Tdrd1	T	C	19: 56,851,484	S659P	possibly damaging	Het
Tead4	T	A	6: 128,242,566	K237N	probably damaging	Het
Tex24	T	A	8: 27,345,124	C227S	probably benign	Het
Tom1	A	T	8: 75,052,168	T174S	probably benign	Het
Tpm3	C	T	3: 90,087,680	R168C	possibly damaging	Het
Trpv3	A	G	11: 73,278,936	E111G	possibly damaging	Het
Unc80	A	G	1: 66,638,032	D2040G	possibly damaging	Het
Usp47	A	G	7: 112,093,195	T955A	probably damaging	Het
Vmn2r11	G	A	5: 109,047,690	A590V	probably damaging	Het
Wisp2	G	T	2: 163,828,866	G98W	probably damaging	Het
Zfp112	A	G	7: 24,125,740	R382G	probably damaging	Het
Zfp606	T	A	7: 12,481,098	D84E	unknown	Het

Other mutations in Alox5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00331:Alox5	APN	6	116415517	missense	probably damaging	1.00
IGL00954:Alox5	APN	6	116454299	missense	probably damaging	1.00
IGL01610:Alox5	APN	6	116413547	missense	probably damaging	1.00
IGL02161:Alox5	APN	6	116423193	missense	probably benign	0.31
IGL02653:Alox5	APN	6	116415477	missense	probably benign	0.41
IGL02903:Alox5	APN	6	116420335	missense	probably damaging	1.00
clanger	UTSW	6	116414595	missense	probably damaging	1.00
nova	UTSW	6	116412549	nonsense	probably null
timpani	UTSW	6	116415456	missense	probably damaging	1.00
Triangle	UTSW	6	116427137	splice site	probably null
R0265:Alox5	UTSW	6	116420362	missense	probably benign	0.04
R0347:Alox5	UTSW	6	116413552	missense	possibly damaging	0.88
R0543:Alox5	UTSW	6	116454317	critical splice acceptor site	probably null
R0633:Alox5	UTSW	6	116420384	missense	probably damaging	1.00
R0656:Alox5	UTSW	6	116423330	splice site	probably benign
R1298:Alox5	UTSW	6	116427264	missense	probably damaging	1.00
R1416:Alox5	UTSW	6	116423145	nonsense	probably null
R1484:Alox5	UTSW	6	116454167	missense	probably damaging	1.00
R1485:Alox5	UTSW	6	116424164	missense	probably damaging	1.00
R1518:Alox5	UTSW	6	116413780	missense	probably damaging	0.99
R1993:Alox5	UTSW	6	116415463	missense	probably damaging	1.00
R2313:Alox5	UTSW	6	116413861	missense	probably benign	0.00
R3125:Alox5	UTSW	6	116427137	splice site	probably null
R4042:Alox5	UTSW	6	116461018	missense	possibly damaging	0.95
R4092:Alox5	UTSW	6	116412674	intron	probably benign
R4356:Alox5	UTSW	6	116420258	missense	probably benign	0.05
R4367:Alox5	UTSW	6	116460963	missense	possibly damaging	0.86
R4690:Alox5	UTSW	6	116423189	missense	probably damaging	1.00
R4792:Alox5	UTSW	6	116461003	missense	possibly damaging	0.94
R4873:Alox5	UTSW	6	116413850	splice site	probably null
R4875:Alox5	UTSW	6	116413850	splice site	probably null
R5135:Alox5	UTSW	6	116413786	missense	probably benign	0.00
R5242:Alox5	UTSW	6	116460966	missense	probably damaging	0.97
R5343:Alox5	UTSW	6	116413507	missense	possibly damaging	0.95
R5780:Alox5	UTSW	6	116420349	missense	probably benign	0.10
R6348:Alox5	UTSW	6	116414595	missense	probably damaging	1.00
R6724:Alox5	UTSW	6	116414548	missense	probably damaging	1.00
R6769:Alox5	UTSW	6	116415184	splice site	probably null
R6954:Alox5	UTSW	6	116420280	nonsense	probably null
R7102:Alox5	UTSW	6	116413468	missense	probably benign	0.01
R7476:Alox5	UTSW	6	116415433	missense	probably benign	0.06
R7626:Alox5	UTSW	6	116413795	missense	possibly damaging	0.94
R7690:Alox5	UTSW	6	116415456	missense	probably damaging	1.00
R7912:Alox5	UTSW	6	116412536	missense	probably benign	0.05
R8234:Alox5	UTSW	6	116413874	missense	probably damaging	0.98
R8787:Alox5	UTSW	6	116413141	missense	probably damaging	0.99
R8910:Alox5	UTSW	6	116412549	nonsense	probably null
R9708:Alox5	UTSW	6	116415576	missense	probably damaging	1.00
X0028:Alox5	UTSW	6	116424154	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATCAGGAGTGCGTATCCAGC -3'
(R):5'- CCCTCACAGATGAATCTACAGTATGG -3'

Sequencing Primer
(F):5'- AGTTCTCAATGTCGGACTCTG -3'
(R):5'- TCTACAGTATGGATATGGACAGC -3'

Posted On

2021-04-30