Mutagenetix > Incidental Mutations

Incidental Mutation 'R2504:Nfkb1'

252099

Institutional Source

Beutler Lab

Gene Symbol

Nfkb1

Ensembl Gene

ENSMUSG00000028163

Gene Name

nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105

Synonyms

p50 subunit of NF kappaB, nuclear factor kappaB p50, NF-kappaB, NF-kappaB p50, p50, p50/p105, NF kappaB1

MMRRC Submission

040412-MU

Accession Numbers

Ncbi RefSeq: NM_008689.2; MGI: 97312

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R2504 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

135584655-135691547 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 135589329 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Arginine at position 918 (I918R)

Ref Sequence

ENSEMBL: ENSMUSP00000128345 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029812] [ENSMUST00000164430] [ENSMUST00000196469]

AlphaFold

P25799

PDB Structure

STRUCTURE OF NF-KB P50 HOMODIMER BOUND TO A KB SITE [X-RAY DIFFRACTION]
IKAPPABALPHA/NF-KAPPAB COMPLEX [X-RAY DIFFRACTION]
Crystal structure of a NF-kB heterodimer bound to an IFNb-kB [X-RAY DIFFRACTION]
Crystal structure of a NF-kB heterodimer bound to the Ig/HIV-kB siti [X-RAY DIFFRACTION]
The kB DNA sequence from the HLV-LTR functions as an allosteric regulator of HIV transcription [X-RAY DIFFRACTION]
STRUCTURE OF THE NUCLEAR FACTOR KAPPA-B (NF-KB) P50 HOMODIMER [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF NF-kB(p50)2 COMPLEXED TO A HIGH-AFFINITY RNA APTAMER [X-RAY DIFFRACTION]
Crystal stucture of WLAC mutant of dimerisation domain of NF-kB p50 transcription factor [X-RAY DIFFRACTION]
Crystal stucture of MLAV mutant of dimerisation domain of NF-kB p50 transcription factor [X-RAY DIFFRACTION]
Crystal stucture of ILAC mutant of dimerisation domain of NF-kB p50 transcription factor [X-RAY DIFFRACTION]
>> 7 additional structures at PDB <<

Predicted Effect

possibly damaging
Transcript: ENSMUST00000029812
AA Change: I918R

PolyPhen 2 Score 0.513 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000029812
Gene: ENSMUSG00000028163
AA Change: I918R

Domain	Start	End	E-Value	Type
Pfam:RHD	42	240	2.9e-75	PFAM
IPT	247	348	1.14e-22	SMART
low complexity region	368	414	N/A	INTRINSIC
ANK	538	568	2.27e1	SMART
ANK	577	606	1.11e-2	SMART
ANK	610	640	2.47e0	SMART
ANK	646	675	5.53e-3	SMART
ANK	680	710	1.9e-1	SMART
ANK	714	743	2.18e-1	SMART
DEATH	801	888	1.9e-19	SMART
low complexity region	890	902	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129428

Predicted Effect

probably benign
Transcript: ENSMUST00000132668

SMART Domains

Protein: ENSMUSP00000114798
Gene: ENSMUSG00000028163

Domain	Start	End	E-Value	Type
low complexity region	8	54	N/A	INTRINSIC
Blast:IPT	55	156	4e-22	BLAST
ANK	178	208	2.27e1	SMART
ANK	217	246	1.11e-2	SMART
ANK	250	280	2.47e0	SMART
ANK	286	315	5.53e-3	SMART
ANK	320	350	1.9e-1	SMART
ANK	354	383	2.18e-1	SMART
Blast:DEATH	441	505	1e-34	BLAST
PDB:2DBF\|A	442	505	5e-32	PDB

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150007

Predicted Effect

possibly damaging
Transcript: ENSMUST00000164430
AA Change: I918R

PolyPhen 2 Score 0.513 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000128345
Gene: ENSMUSG00000028163
AA Change: I918R

Domain	Start	End	E-Value	Type
Pfam:RHD_DNA_bind	42	240	2.9e-75	PFAM
IPT	247	348	1.14e-22	SMART
low complexity region	368	414	N/A	INTRINSIC
ANK	538	568	2.27e1	SMART
ANK	577	606	1.11e-2	SMART
ANK	610	640	2.47e0	SMART
ANK	646	675	5.53e-3	SMART
ANK	680	710	1.9e-1	SMART
ANK	714	743	2.18e-1	SMART
DEATH	801	888	1.9e-19	SMART
low complexity region	890	902	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000184550

Predicted Effect

probably benign
Transcript: ENSMUST00000196469

SMART Domains

Protein: ENSMUSP00000143601
Gene: ENSMUSG00000028163

Domain	Start	End	E-Value	Type
Pfam:RHD_DNA_bind	42	90	2.5e-19	PFAM

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.4%
20x: 95.4%

Validation Efficiency

MGI Phenotype

Strain: 1857225
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Feb 2016]
PHENOTYPE: Homozygous null mice have a decreased survivor rate, abnormal T cell development and decreased number of peripheral T cells, abnormal humoral responses with decreased immunoglobulin class switching, exhibit mild organ inflammation, and are susceptible toboth bacterial infections and hearing loss. [provided by MGI curators]

Allele List at MGI

All alleles(79) : Targeted(5) Gene trapped(74)

Other mutations in this stock

Total: 113 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410089E03Rik	G	A	15: 8,219,216	E1750K	probably damaging	Het
4933425L06Rik	A	G	13: 105,109,742	I270M	probably benign	Het
Aatk	T	C	11: 120,018,855	D28G	probably benign	Het
Abcg1	T	A	17: 31,092,395	S125T	probably damaging	Het
Actbl2	T	C	13: 111,256,183	S351P	possibly damaging	Het
Ankrd34b	A	G	13: 92,439,061		probably null	Het
BC030867	T	C	11: 102,255,296	Y133H	possibly damaging	Het
BC051665	C	T	13: 60,782,654	V295I	probably benign	Het
C1qtnf2	A	G	11: 43,491,156	N265S	probably damaging	Het
Ccdc14	C	T	16: 34,721,850	R573*	probably null	Het
Cd55b	A	T	1: 130,409,875	Y247N	probably damaging	Het
Celsr2	A	T	3: 108,413,591	V635E	probably benign	Het
Clec16a	T	C	16: 10,559,687		probably benign	Het
Clec4b1	A	G	6: 123,065,945	Y41C	probably damaging	Het
Cntn5	A	T	9: 10,172,121	D19E	probably benign	Het
Cop1	A	G	1: 159,232,805	N53S	probably damaging	Het
Csad	A	T	15: 102,188,667	M1K	probably null	Het
Cyb5rl	A	G	4: 107,080,945	I200V	probably benign	Het
Cyp26a1	A	G	19: 37,698,342	T81A	probably damaging	Het
Cyp2d12	A	T	15: 82,559,036	H433L	probably benign	Het
D7Ertd443e	T	A	7: 134,349,479		probably null	Het
Dennd1b	A	G	1: 139,170,170		probably benign	Het
Dmap1	G	T	4: 117,675,298	T357K	probably damaging	Het
Dzip1	G	T	14: 118,881,044	T759K	probably benign	Het
Elmo2	A	G	2: 165,298,687	V300A	probably damaging	Het
Eml5	T	C	12: 98,844,105	D864G	possibly damaging	Het
Ep400	A	G	5: 110,668,645	V2670A	probably damaging	Het
Epha3	T	A	16: 63,603,625	I534F	probably damaging	Het
Epha4	A	C	1: 77,382,991	Y742D	probably damaging	Het
Ergic2	A	G	6: 148,204,774		probably null	Het
Ero1l	A	T	14: 45,299,088		probably null	Het
Fam229a	A	G	4: 129,491,486	D70G	probably damaging	Het
Fbn2	C	T	18: 58,093,359	R781Q	probably damaging	Het
Fbxo16	A	T	14: 65,270,714		probably benign	Het
Fbxo39	T	A	11: 72,317,285	S154R	probably benign	Het
Fer	T	A	17: 63,991,580		probably null	Het
Filip1l	A	G	16: 57,570,662	I538V	possibly damaging	Het
Filip1l	A	T	16: 57,571,047	D428V	probably damaging	Het
Fsip2	T	C	2: 82,979,610	I2091T	possibly damaging	Het
Glyat	A	C	19: 12,651,398	T186P	possibly damaging	Het
Gm10604	A	G	4: 11,980,083	S74P	unknown	Het
Gm4787	T	G	12: 81,379,137	K82N	possibly damaging	Het
Hectd4	T	C	5: 121,220,620	I50T	unknown	Het
Hectd4	T	C	5: 121,263,967	S373P	possibly damaging	Het
Hmcn1	A	T	1: 150,686,867	C2313*	probably null	Het
Igfn1	A	T	1: 135,969,316	S1171T	probably benign	Het
Ints8	T	C	4: 11,241,642	D267G	probably benign	Het
Itln1	A	G	1: 171,529,159	C251R	probably damaging	Het
Jcad	C	T	18: 4,674,026	T596M	probably damaging	Het
Kcnj16	C	T	11: 111,025,583	T357M	probably benign	Het
Kif13a	G	A	13: 46,814,200	T346M	probably damaging	Het
Klhl24	G	A	16: 20,120,167	A491T	probably benign	Het
Kntc1	C	T	5: 123,778,347	Q748*	probably null	Het
Krt25	T	A	11: 99,317,296	K369*	probably null	Het
Krt75	C	T	15: 101,568,031	R433Q	probably benign	Het
Krt76	A	G	15: 101,884,858	F582L	unknown	Het
Lysmd1	G	A	3: 95,138,397	V182I	probably benign	Het
Mab21l2	T	A	3: 86,547,555	E46V	probably damaging	Het
Magi2	A	T	5: 20,358,936	K355N	probably damaging	Het
March10	T	C	11: 105,385,572	D630G	probably damaging	Het
Mast4	A	T	13: 102,738,639	I1215N	probably damaging	Het
Nckap1	G	A	2: 80,530,218	T523I	probably benign	Het
Nexmif	T	A	X: 104,084,393	D1306V	probably damaging	Het
Nup50	A	T	15: 84,933,658	T93S	probably benign	Het
Nwd2	T	C	5: 63,804,374	Y434H	probably benign	Het
Olfr61	T	C	7: 140,638,484	V261A	probably benign	Het
Osbpl1a	C	A	18: 12,905,031	V288L	probably benign	Het
Pan3	A	G	5: 147,527,036	E562G	possibly damaging	Het
Pappa	T	A	4: 65,180,889	Y548*	probably null	Het
Phf3	A	T	1: 30,810,789	L1181Q	probably damaging	Het
Phip	T	C	9: 82,915,339	H537R	possibly damaging	Het
Pkhd1l1	T	C	15: 44,485,428	I240T	probably damaging	Het
Pole	G	A	5: 110,290,502		probably null	Het
Polq	T	A	16: 37,011,942	S15T	unknown	Het
Prrt2	T	C	7: 127,020,224	E23G	possibly damaging	Het
Prss37	A	T	6: 40,517,826		probably null	Het
Prune2	T	C	19: 17,000,036	L45P	probably damaging	Het
Psd	A	T	19: 46,324,913	M6K	possibly damaging	Het
Psmd1	A	G	1: 86,089,997	E510G	possibly damaging	Het
Ptch1	T	G	13: 63,524,959	E944A	probably benign	Het
Pxdn	T	A	12: 30,003,406	I1194N	probably damaging	Het
Rbp3	C	T	14: 33,956,018	T641M	probably damaging	Het
Rgmb	C	A	17: 15,807,647	R270L	probably benign	Het
Rpgrip1l	A	G	8: 91,280,716		probably null	Het
Rps2	G	A	17: 24,720,379		probably benign	Het
Rsbn1l	G	T	5: 20,902,366	A550E	probably damaging	Het
S1pr4	C	T	10: 81,499,304	R112H	probably benign	Het
Scfd2	T	C	5: 74,531,177	N148S	probably damaging	Het
Scin	C	T	12: 40,081,706	M276I	probably benign	Het
Sec24d	T	C	3: 123,353,606	I708T	possibly damaging	Het
Skint11	T	A	4: 114,228,812	F41I	possibly damaging	Het
Slc15a4	A	T	5: 127,617,239	F44Y	possibly damaging	Het
Slc6a18	A	G	13: 73,675,806	Y72H	probably benign	Het
Slc7a11	A	T	3: 50,377,746		probably null	Het
Slc7a14	G	T	3: 31,237,501	N209K	possibly damaging	Het
Sstr2	T	C	11: 113,624,431	C59R	probably damaging	Het
Stab1	A	G	14: 31,163,040		probably null	Het
Stag1	G	T	9: 100,866,210	S475I	probably damaging	Het
Stxbp5l	A	G	16: 37,115,667	Y1183H	probably damaging	Het
Svep1	A	T	4: 58,135,628		probably null	Het
Tm9sf2	A	G	14: 122,158,684	T653A	probably benign	Het
Tmeff1	T	C	4: 48,662,059	S366P	possibly damaging	Het
Tnnt2	G	T	1: 135,852,065	W300L	probably damaging	Het
Traj32	A	G	14: 54,186,103		probably benign	Het
Trp53bp2	A	T	1: 182,441,639	M223L	probably benign	Het
Tsga10	G	A	1: 37,815,677	T246M	probably damaging	Het
Txn2	A	T	15: 77,926,670		probably benign	Het
Ubr3	T	A	2: 69,938,198	F450I	probably damaging	Het
Usp47	T	C	7: 112,104,470		probably null	Het
Vars2	C	T	17: 35,664,793	R244Q	probably damaging	Het
Xrra1	T	A	7: 99,897,596	F251L	probably damaging	Het
Zfp804a	G	A	2: 82,257,519	R564Q	probably benign	Het
Zfp983	T	C	17: 21,658,967	C29R	probably damaging	Het

Other mutations in Nfkb1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01293:Nfkb1	APN	3	135590839	missense	probably damaging	1.00
IGL01345:Nfkb1	APN	3	135594981	missense	probably damaging	1.00
IGL01629:Nfkb1	APN	3	135601467	missense	probably benign
IGL02216:Nfkb1	APN	3	135594963	missense	probably damaging	0.98
IGL02273:Nfkb1	APN	3	135605207	missense	probably benign	0.01
IGL02508:Nfkb1	APN	3	135590818	missense	probably damaging	0.99
IGL03095:Nfkb1	APN	3	135618830	missense	possibly damaging	0.48
Conversely	UTSW	3	135626659	missense	probably damaging	1.00
Finlay	UTSW	3	135595053	nonsense	probably null
Frisbee	UTSW	3	135613943	missense	possibly damaging	0.93
Honeyeater	UTSW	3	135591551	splice site	probably benign
kookaburra	UTSW	3	135626611	nonsense	probably null
Murgatroyd	UTSW	3	135626710	missense	possibly damaging	0.72
Poderoso	UTSW	3	135613990	missense	probably damaging	1.00
Puff	UTSW	3	135595053	nonsense	probably null
Roomba	UTSW	3	135612412	critical splice donor site	probably null
Wheelo	UTSW	3	135615349	missense	possibly damaging	0.81
R0026:Nfkb1	UTSW	3	135591573	missense	probably damaging	1.00
R0047:Nfkb1	UTSW	3	135595053	nonsense	probably null
R0989:Nfkb1	UTSW	3	135589396	missense	probably benign	0.00
R1210:Nfkb1	UTSW	3	135594927	missense	probably benign	0.03
R1661:Nfkb1	UTSW	3	135594957	missense	probably damaging	1.00
R1665:Nfkb1	UTSW	3	135594957	missense	probably damaging	1.00
R1725:Nfkb1	UTSW	3	135667758	missense	probably damaging	1.00
R1984:Nfkb1	UTSW	3	135615349	missense	possibly damaging	0.81
R1985:Nfkb1	UTSW	3	135615349	missense	possibly damaging	0.81
R2154:Nfkb1	UTSW	3	135601479	missense	probably benign	0.44
R2281:Nfkb1	UTSW	3	135601521	missense	probably damaging	1.00
R2409:Nfkb1	UTSW	3	135613943	missense	possibly damaging	0.93
R4032:Nfkb1	UTSW	3	135594349	missense	possibly damaging	0.63
R4232:Nfkb1	UTSW	3	135603770	missense	probably damaging	1.00
R4936:Nfkb1	UTSW	3	135613982	missense	probably damaging	0.97
R5085:Nfkb1	UTSW	3	135603807	missense	probably benign	0.36
R5262:Nfkb1	UTSW	3	135612412	critical splice donor site	probably null
R5384:Nfkb1	UTSW	3	135612542	missense	possibly damaging	0.95
R5385:Nfkb1	UTSW	3	135612542	missense	possibly damaging	0.95
R5434:Nfkb1	UTSW	3	135626611	nonsense	probably null
R5663:Nfkb1	UTSW	3	135603851	missense	possibly damaging	0.88
R5865:Nfkb1	UTSW	3	135603780	missense	probably damaging	1.00
R6006:Nfkb1	UTSW	3	135603761	nonsense	probably null
R6013:Nfkb1	UTSW	3	135626684	missense	possibly damaging	0.86
R6234:Nfkb1	UTSW	3	135626710	missense	possibly damaging	0.72
R6785:Nfkb1	UTSW	3	135615303	missense	probably benign
R7175:Nfkb1	UTSW	3	135613990	missense	probably damaging	1.00
R7227:Nfkb1	UTSW	3	135626659	missense	probably damaging	1.00
R7394:Nfkb1	UTSW	3	135613697	missense	possibly damaging	0.54
R7727:Nfkb1	UTSW	3	135585401	missense	possibly damaging	0.48
R7815:Nfkb1	UTSW	3	135603791	missense	probably damaging	1.00
R7849:Nfkb1	UTSW	3	135585412	missense
R8004:Nfkb1	UTSW	3	135591551	splice site	probably benign
R8059:Nfkb1	UTSW	3	135593852	missense	possibly damaging	0.54
R8806:Nfkb1	UTSW	3	135589452	missense	probably damaging	1.00
R9169:Nfkb1	UTSW	3	135605113	missense	probably benign	0.00
X0050:Nfkb1	UTSW	3	135606623	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CAATGTGAGTGTCTGTGGGAAC -3'
(R):5'- TGCAAACAGGCTGGAACAC -3'

Sequencing Primer
(F):5'- GAACTGCCTGTTCCTGTGTGC -3'
(R):5'- GGCTGGAACACACGAACATACTC -3'

Posted On

2014-12-04