Genomic Structure and Variation of Nuclear Factor (Erythroid-Derived 2)-Like 2

Table 3

Genetic mutations in promoter and exons of human NRF2.

ID	Map on chromosome 2*; (HGVS name)	Position in Nfe2l2 ^#; (HGVS name)	Regions; (position from mRNA)^#	Variation class and consequences; (HGVS name)^†	Minor allele frequency (MAF)/; MA counts^‡ (cohort size)	MAF sources
rs16865105	g.178136629A>C	c.−555−6770T>G	5′Flanking (−6770)	SNP	C = 0.1928/421	1000 Genomes
rs7557529	g.178135097C>T	c.−555−5238G>A	5′Flanking (−5238)	SNP	na
rs6750320	g.178131796C>T	c.−555−1937G>A	5′Flanking (−1937)	SNP	T = 0.0302/66	1000 Genomes
rs181162518	g.178131774T>C	c.−555−1915A>G	5′Flanking (−1915)	SNP	C = 0.0005/1	1000 Genomes
rs190044775	g.178131746C>T	c.−555−1887G>A	5′Flanking (−1887)	SNP	T = 0.0005/1	1000 Genomes
rs185117338	g.178131704A>G	c.−555−1845T>C	5′Flanking (−1845)	SNP	G = 0.0005/1	1000 Genomes
rs149947189	g.178131697C>T	c.−555−1838G>A	5′Flanking (−1838)	SNP	T = 0.0009/2	1000 Genomes
rs139771244	g.178131625A>G	c.−555−1766T>C	5′Flanking (−1766)	SNP	G = 0.0009/2	1000 Genomes
rs6747203	g.178131604C>G	c.−555−1745G>C	5′Flanking (−1745)	SNP	G = 0.006/13	1000 Genomes
rs193101749	g.178131504T>C	c.−555−1645A>G	5′Flanking (−1645)	SNP	C = 0.0046/10	1000 Genomes
rs190630762	g.178131495G>C	c.−555−1636C>G	5′Flanking (−1636)	SNP	C = 0.0009/2	1000 Genomes
rs183764402	g.178131366C>A	c.−555−1507G>T	5′Flanking (−1507)	SNP	A = 0.0005/1	1000 Genomes
rs191222964	g.178131211G>A	c.−555−1352C>T	5′Flanking (−1352)	SNP	A = 0.0009/2	1000 Genomes
rs187137522	g.178131165T>G	c.−555−1306A>C	5′Flanking (−1306)	SNP	G = 0.0009/2	1000 Genomes
rs182620359	g.178131158A>G	c.−555−1299T>C	5′Flanking (−1299)	SNP	G = 0.0005/1	1000 Genomes
rs4893819 (rs61433302)	g.178131134C>T	c.−555−1275G>A	5′Flanking (−1275)	SNP	C = 0.4263/931	1000 Genomes
rs191547130	g.178131017C>T	c.−555−1158G>A	5′Flanking (−1158)	SNP	T = 0.0005/1	1000 Genomes
rs188422217	g.178131003A>G	c.−555−1144T>C	5′Flanking (−1144)	SNP	G = 0.0014/3	1000 Genomes
rs143047764	g.178130865A>G	c.−555−1006T>C	5′Flanking (−1006)	SNP	G = 0.0069/15	1000 Genomes
rs74432849	g.178130766C>A	c.−555−907G>T	5′Flanking (−907)	SNP	na
rs11679252	g.178130691C>G	c.−555−832G>C	5′Flanking (−832)	SNP	na
rs12993217	g.178130516A>G	c.−555−657T>C	5′Flanking (−657)	SNP	na
rs115644826	g.178130442T>A	c.−555−583A>T	5′Flanking (−583)	SNP	A = 0.0151/33	1000 Genomes
rs140803524	g.178130431G>A	c.−555−572C>T	5′Flanking (−572)	SNP	A = 0.0046/10	1000 Genomes
rs77684420	g.178130427T>C	c.−555−568A>G	5′Flanking (−568)	SNP	C = 0.0339/74; C = 0.190 (84)	1000 Genomes; [24]
rs183651094	g.178130336A>T	c.−555−477T>A	5′Flanking (−477)	SNP	T = 0.0018/4	1000 Genomes
rs35652124^§ (rs57695243)	g.178130073T>C	c.−555−214A>G	5′Flanking (−214)	SNP	C = 0.3512/767; T = 0.429 (84); T = 0.413/181^‡; C = 0.338/27^‡; C = 0.351/769	1000 Genomes; [24]; [22]; [23]; [25]
rs6706649^§	g.178130071C>T	c.−555−212G>A	5′Flanking (−212)	SNP	T = 0.078/170; T = 0.048 (84); T = 0.048/21^‡; T = 0.075/3^‡	1000 Genomes; [24]; [22]; [23]
rs150648896	g.178130047C>G	c.−555−188G>C	5′Flanking (−188)	SNP	G = 0.0023/5; G = 0.006 (84)	1000 Genomes; [24]
rs6721961^§ (rs117801448)	g.178130037T>C, T>G	c.−555−178A>C, A>G	5′Flanking (−178)	SNP	T = 0.150/328; T = 0.283/124^‡; T = 0.313/25^‡; T = 0.321 (84)	1000 Genomes; [22]; [23]; [24]
rs201345604	g.178129924_178129925insG	c.−555-66_−555-65insC	5′Flanking (−66/−65)	Insertion	G = 0.0179/39	1000 Genomes
rs200432479	g.178129741_178; 129742delAA	c.−438_−437delTT	exon 1/UTR-5′(118−119)	Deletion	- = 0.0037/8; - = 0.006 (84)	1000 Genomes; [24]
rs75485459	g.178129608C>A	c.−304G>T	Exon 1/UTR-5′ (252)	SNP	na
rs192086766	g.178129466C>T	c.−162G>A	Exon 1/UTR-5′ (394)	SNP	T = 0.022/48	1000 Genomes
—	g.178129442G>A	c.−138C>T	Exon 1/UTR-5′ (418)	SNP	A = 0.012 (84)	[24]
rs71668246	g.178129400delG	c.−96delC	Exon 1/UTR-5′ (460)	Deletion	na
rs187291840	g.178129399C>T	c.−95G>A	Exon 1/UTR-5′ (461)	SNP	T = 0.0549/120	1000 Genomes
rs143406266	g.178129391_178129393delGGC	c.−89_−87delGCC	Exon 1/UTR-5′ (467−469)	Deletion	- = 0.644/282^‡; - = 0.589 (84)	[22]; [24]
rs182428269	g.178098918G>A	c.127C>T	Exon 2 (682)	Cns (p.Arg43Trp)	A = 0.0005/1	1000 Genomes
rs35248500	g.178098917C>T	c.128G>A	Exon 2 (683)	Cns (p.Arg43Gln)	T = 0.006/13	1000 Genomes
rs1135118	g.178098831C>T	c.214G>A	Exon 2 (769)	Cns (p.Ala72Thr)	T^‡	[23]
rs199691660	g.178098829A>T	c.216T>A	Exon 2 (771)	Cs (p.Ala72=)	na
—	g.178098769G>A	c.276C>T	Exon 2 (831)	Cs (p. Ile 92=)	T^‡	[23]
rs5031039	g.178098750A>G	c.295T>C	Exon 2 (850)	Cns (p.Ser99Pro)	G = 0^‡	[23]
rs200239262	g.178098017C>G	c.363G>C	Exon 3 (918)	Cns (p.Gln121His)	na
rs183034165	g.178098008T>C	c.372G>A	Exon 3 (927)	Cs (p.Ala124=)	T = 0.0009/2; T = 0.006 (84)	1000 Genomes; [24]
rs199970826	g.178097996C>T	c.384G>A	Exon 3 (939)	Cs (p.Pro128=)	T = 0.0005/1	1000 Genomes
rs201992337	g.178097260C>T	c.454G>A	Exon 4 (1009)	Cns (p.Glu152Lys)	na
rs201589693	g.178097251C>T	c.463G>A	Exon 4 (1018)	Cns (p.Val155Ile)	T = 0.0005/1	1000 Genomes
rs35577826	g.178097185A>C	c.529T>G	Exon 4 (1084)	Cns (p.Leu177Val)	C = 0.0014/3; A < 0.005^‡	1000 Genomes; [23]
rs181513314	g.178096710C>T	c.621G>A	Exon 5 (1176)	Cn (p.Leu207=)	T = 0.0005/1	1000 Genomes
rs60132461	g.178096675T>C	c.656A>G	Exon 5 (1211)	Cns (p.Lys219Arg)	C = 0.0018/4	1000 Genomes
rs139187151	g.178096634G>A	c.697C>T	Exon 5 (1252)	Cns (p.Pro233Ser)	A = 0.0005/1; A = 0.012^‡ (84)	1000 Genomes; [24]
rs35557421	g.178096620delT	c.711delA	Exon 5 (1266)	Frame shift/deletion (p.Lys237 = fs)	na
rs34154613	g.178096529C>T	c.802G>A	Exon 5 (1357)	Cns (p.Val268Met)	T = 0.0018/4	1000 Genomes
rs141363120	g.178096406G>A	c.925C>T	Exon 5 (1480)	Cns (p.Leu309Phe)	A = 0.0037/8	1000 Genomes
rs201661476	g.178096380A>C	c.951T>G	Exon 5 (1506)	Cns (p.Ile317Met)	na
rs199673454	g.178096309T>A	c.1022A>T	Exon 5 (1577)	Cns (p.Asp341Val)	A = 0.0005/1	1000 Genomes
rs35007548	g.178096299G>A	c.1032C>T	Exon 5 (1587)	Cs (p.Ser344=)	A = 0.0009/2	1000 Genomes
rs200209692	g.178096287T>C	c.1044A>G	Exon 5 (1599)	Cs (p.Leu348=)	C = 0.0005/1	1000 Genomes
—	g.178096237C>A	c.1094G>T	Exon 5 (1649)	Cns (p.Ser365Ile)	A = 0.125/273; A = 0.006^‡ (84)	PubMed; [24]
rs201214197	g.178096171C>T	c.1160G>A	Exon 5 (1715)	Cns (p.Ser387Asn)	T = 0.0005/1	1000 Genomes
rs200494292	g.178096165T>C	c.1166A>G	Exon 5 (1721)	Cns (p.Lys389Arg)	na
rs186171287	g.178096115G>A	c.1216C>T	Exon 5 (1771)	Cns (p.Pro406Ser)	A = 0.0005/1	1000 Genomes
rs182276775	g.178096062C>A	c.1269G>T	Exon 5 (1824)	Cns (p.Glu423Asp)	A = 0.0005/1	1000 Genomes
rs201560221	g.178096048T>C	c.1283A>G	Exon 5 (1838)	Cns (p.Lys428Arg)	na
rs189238236	g.178096043A>G	c.1288T>C	Exon 5 (1843)	Cs (p.Leu430=)	G = 0.0005/1	1000 Genomes
rs184287392	g.178096022G>A	c.1309C>T	Exon 5 (1864)	Cns (p.Arg437Trp)	A = 0.0005/1	1000 Genomes
rs201871588	g.178095986G>A	c.1345C>T	Exon 5 (1900)	Cns (p.Ag449Cys)	na
rs181294188	g.178095985T>C	c.1346G>A	Exon 5 (1901)	Cns (p.Arg449His)	T = 0.0009/2	1000 Genomes
rs201690466	g.178095973T>A	c.1358A>T	Exon 5 (1913)	Cns (p.His453Leu)	A = 0.0005/1	1000 Genomes
rs1057044 (rs52789869)	g.178095781C>T	c.1550G>A	Exon 5 (2105)	Cns (p.Arg517Lys)	T^‡	[23]
rs200750800	g.178095603A>G	c.1728T>C	Exon 5 (2283)	Cs (p.Tyr576=)	na
rs200175942	g.178095567A>G	c.1764T>C	Exon 5 (2319)	Cs (p.Asp588=)	G = 0.0005/1	1000 Genomes
rs77547666	g.178095495G>C	c.*18C>G	Exon 5/UTR-3′ (2391)	SNP	C = 0.0069/15	1000 Genomes
rs73031353	g.178095425T>C	c.*88A>G	Exon 5/UTR-3′ (2461)	SNP	C = 0.0018/4	1000 Genomes
rs6759443	g.178095345T>C	c.*168A>G	Exon 5/UTR-3′ (2541)	SNP	C = 0.0041/9	1000 Genomes
rs188674558	g.178095279C>A	c.*234G>T	Exon 5/UTR-3′ (2607)	SNP	A = 0.0005/1	1000 Genomes
rs77685897	g.178095247A>G	c.*266T>C	Exon 5/UTR-3′ (2639)	SNP	G = 0.0009/2	1000 Genomes
rs1057092	g.178095162T>G	c.*351A>C	Exon 5/UTR-3′ (2724)	SNP	na
rs3197704	g.178095162T>G	c*351A>C	Exon 5/UTR-3′ (2724)	SNP	na
rs184701151	g.178095159T>C	c.*354A>G	Exon 5/UTR-3′ (2727)	SNP	C = 0.0027/6	1000 Genomes
rs11543307	g.178095153A>G	c.*360T>C	Exon 5/UTR-3′ (2733)	SNP	na
rs111874043	g.178095146A>G	c.*367T>C	Exon 5/UTR-3′ (2740)	SNP	na
rs34012004	g.178095102A>C	c.*411T>G	Exon 5/UTR-3′ (2784)	SNP	C = 0.071	[24]
rs201481890	g.178095090_178095091insT	c.*422_*423insA	Exon 5/UTR-3′ (2795−2796)	Insertion	na
rs3082500	g.178095089_178095090delTT,; delTTinsT	c.*423_*424delA; AinsA	Exon 5/UTR-3′ (2796−2797)	Deletion, insertion	na
rs71792546 (rs71796710)	g.178095079delT	c.*425delA	Exon 5/UTR-3′ (2798)	Deletion	na
rs1057106	g.178095078A>C, A>T	c.*435T>A,; T>G	Exon 5/UTR-3′ (2808)	SNP	na
rs34176791	g.178095076A>C	c.*437T>G	Exon 5/UTR-3′ (2810)	SNP	C = 0.0023/5	1000 Genomes
rs35911553	g.178095045C>T	c.*468G>A	Exon 5/UTR-3′ (2841)	SNP	T = 0.0069/15	1000 Genomes

Sequence variations in upstream and exons of human NRF2 from 655 variations available in public database as of December, 2012 (583 active, some SNPs merged, ≥14 SNPs cited in PubMed). *NCBI reference sequence NC_000002.11 (Homosapiens chromosome 2, GRCh37.p10 primary assembly) spanning 178,095,033–178,129,859 bp (complement, 34,827 bp for exons and introns). 5′-Flanking regions start at 178,129,860 bp (−1) in transcript variant 1. HGVS: Human Genome Variation Society. ^#Positions in variant 1 (NM_006164.4), 2859 bp. §SNPs cited in PubMed. Exon 1: 178,129,859–178,129,260 (600 bp, TTS = 178,129,304), exon 2: 178,098,999–178,098,733 (267 bp), exon 3: 178,098,067–178,097,978 (90 bp), exon 4: 178,097,311–178,097,120 (192 bp), and exon 5: 178,096,736–178,095,033 (1704 bp). ^†Protein amino acid (aa) residues in isoform 1 (NP_006155.2, 605 aa). Cns: coding-nonsynonymous. Cs: coding-synonymous.^‡heterozygosity detected. na: not available.