Mutagenetix > Incidental Mutation

Incidental Mutation 'R1899:Polr2a'

214118

Institutional Source

Beutler Lab

Gene Symbol

Polr2a

Ensembl Gene

ENSMUSG00000005198

Gene Name

polymerase (RNA) II (DNA directed) polypeptide A

Synonyms

Rpo2-1, 220kDa

MMRRC Submission

039919-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.967) question?

Stock #

R1899 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

69733997-69758637 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 69743946 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 636 (I636N)

Ref Sequence

ENSEMBL: ENSMUSP00000071200 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000058470] [ENSMUST00000071213]

AlphaFold

P08775

Predicted Effect

probably damaging
Transcript: ENSMUST00000058470
AA Change: I636N

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000050771
Gene: ENSMUSG00000005198
AA Change: I636N

Domain	Start	End	E-Value	Type
Blast:RPOLA_N	110	179	5e-37	BLAST
RPOLA_N	246	549	7.02e-203	SMART
Pfam:RNA_pol_Rpb1_4	716	823	3.6e-39	PFAM
Pfam:RNA_pol_Rpb1_5	830	1428	2e-101	PFAM
Pfam:RNA_pol_Rpb1_6	896	1079	1.7e-70	PFAM
Pfam:RNA_pol_Rpb1_7	1164	1299	1.7e-57	PFAM
Pfam:RNA_pol_Rpb1_R	1555	1568	2.1e-3	PFAM
Pfam:RNA_pol_Rpb1_R	1616	1629	8.8e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1630	1643	1.9e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1644	1657	2.3e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1658	1671	2.2e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1672	1685	2.4e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1686	1699	2.5e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1700	1713	2.5e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1714	1727	2.5e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1728	1741	2.6e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1742	1755	5.3e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1757	1769	5.8e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1784	1797	2.6e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1798	1811	4.8e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1826	1839	4.3e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1841	1853	2e-3	PFAM
Pfam:RNA_pol_Rpb1_R	1854	1867	6.9e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1868	1881	3.7e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1882	1895	1.2e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1896	1909	5e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1910	1923	2.5e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1924	1936	2e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1931	1954	2.6e-3	PFAM
Pfam:RNA_pol_Rpb1_R	1948	1960	2.5e-3	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000071213
AA Change: I636N

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000071200
Gene: ENSMUSG00000005198
AA Change: I636N

Domain	Start	End	E-Value	Type
Blast:RPOLA_N	110	179	5e-37	BLAST
RPOLA_N	246	549	7.02e-203	SMART
Pfam:RNA_pol_Rpb1_4	716	823	1.8e-41	PFAM
Pfam:RNA_pol_Rpb1_5	830	1428	4.8e-104	PFAM
Pfam:RNA_pol_Rpb1_6	896	1079	5.2e-74	PFAM
Pfam:RNA_pol_Rpb1_7	1164	1299	1.4e-55	PFAM
low complexity region	1503	1522	N/A	INTRINSIC
low complexity region	1524	1549	N/A	INTRINSIC
Pfam:RNA_pol_Rpb1_R	1578	1591	2.7e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1592	1605	2.5e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1606	1619	2.7e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1620	1633	2.5e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1634	1647	2.5e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1648	1661	2.4e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1662	1675	2.4e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1676	1689	2.6e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1690	1703	2.3e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1704	1717	5.2e-7	PFAM
Pfam:RNA_pol_Rpb1_R	1718	1731	5.5e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1732	1745	1.6e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1746	1759	8.6e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1760	1773	2e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1788	1801	3.3e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1802	1815	2.4e-4	PFAM
Pfam:RNA_pol_Rpb1_R	1816	1829	8.3e-7	PFAM
Pfam:RNA_pol_Rpb1_R	1830	1843	2.2e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1844	1857	1.6e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1858	1871	2.8e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1872	1885	6e-7	PFAM
Pfam:RNA_pol_Rpb1_R	1886	1899	4.6e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1893	1909	4.8e-5	PFAM
Pfam:RNA_pol_Rpb1_R	1903	1916	2.8e-6	PFAM
Pfam:RNA_pol_Rpb1_R	1910	1923	1.6e-4	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151586

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 97.5%
3x: 97.0%
10x: 95.6%
20x: 93.4%

Validation Efficiency

94% (94/100)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a carboxy terminal domain composed of heptapeptide repeats that are essential for polymerase activity. These repeats contain serine and threonine residues that are phosphorylated in actively transcribing RNA polymerase. In addition, this subunit, in combination with several other polymerase subunits, forms the DNA binding domain of the polymerase, a groove in which the DNA template is transcribed into RNA. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for a reporter allele show prenatal lethality. Homozygotes for a small deletion in the C-terminal domain are viable, fertile and developmentally normal. Homozygotes for a larger deletion show reduced fetal size and partial postnatal lethality; survivors are small but otherwise normal. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610009O20Rik	T	C	18: 38,258,342	W378R	probably benign	Het
4930522L14Rik	T	A	5: 109,736,798	Q398L	probably benign	Het
4930596D02Rik	T	G	14: 35,810,132	K162T	probably damaging	Het
Abca8b	G	T	11: 109,937,918	T1353K	possibly damaging	Het
Abcg3	A	C	5: 104,938,199	C565G	probably damaging	Het
Actr3b	G	A	5: 25,829,538	V185I	possibly damaging	Het
Akap6	A	T	12: 53,141,852	E2016D	possibly damaging	Het
Aldh3b2	T	C	19: 3,978,662	V148A	possibly damaging	Het
Ankfy1	C	T	11: 72,754,407	Q771*	probably null	Het
Anks1b	A	G	10: 90,260,756	D425G	probably damaging	Het
Arrb1	T	C	7: 99,582,297		probably benign	Het
Atg2a	C	A	19: 6,245,067	T170N	probably damaging	Het
Atp8b5	C	T	4: 43,361,804	R617C	possibly damaging	Het
Bicra	T	C	7: 15,987,751	T614A	possibly damaging	Het
Cacna1i	A	G	15: 80,391,642	D167G	possibly damaging	Het
Calr4	T	G	4: 109,246,293		probably null	Het
Camsap3	G	T	8: 3,603,922	E515*	probably null	Het
Casp8ap2	T	C	4: 32,643,647	S907P	probably damaging	Het
Cdk19	T	A	10: 40,479,780		probably benign	Het
Chst14	A	G	2: 118,927,015	M122V	possibly damaging	Het
Cntn4	A	G	6: 106,675,813	M748V	probably benign	Het
Col7a1	A	G	9: 108,978,888	D2552G	unknown	Het
Cpeb2	C	A	5: 43,277,587	P600Q	probably damaging	Het
Cyp2a5	C	T	7: 26,839,033	R274*	probably null	Het
Dexi	A	G	16: 10,542,518	F58S	probably damaging	Het
Dlg5	C	A	14: 24,148,300	G1522W	probably damaging	Het
Dock2	T	C	11: 34,294,286	H1048R	probably benign	Het
Dpp4	T	C	2: 62,345,050		probably benign	Het
Dusp10	A	T	1: 184,069,180	K381N	possibly damaging	Het
Ercc4	A	G	16: 13,147,787	E761G	probably damaging	Het
Ern2	T	C	7: 122,183,842		probably benign	Het
Fam83f	A	T	15: 80,692,080	T311S	probably damaging	Het
Fat2	T	C	11: 55,262,178	D3736G	probably benign	Het
Fgf11	G	T	11: 69,801,453	T58K	probably benign	Het
Galntl5	C	G	5: 25,198,532	S167*	probably null	Het
Glg1	T	G	8: 111,165,674	E846D	probably benign	Het
Grm8	C	A	6: 28,125,895	E77D	probably damaging	Het
Hmcn1	A	T	1: 150,657,451	D3028E	probably damaging	Het
Htt	A	G	5: 34,907,085	I2943V	probably benign	Het
Ift80	T	C	3: 68,918,513	K498R	probably benign	Het
Ipo9	A	T	1: 135,400,146	M509K	probably damaging	Het
Kcnj3	T	C	2: 55,437,244	V15A	probably damaging	Het
Kcnn3	A	T	3: 89,520,455		probably benign	Het
Larp1b	T	A	3: 40,964,084	D53E	probably benign	Het
Ltf	T	C	9: 111,022,845	F117L	possibly damaging	Het
Maml1	A	G	11: 50,266,130	L406P	probably damaging	Het
Mnx1	G	A	5: 29,473,957	A376V	unknown	Het
Mroh2a	G	A	1: 88,235,376	R376H	probably benign	Het
Mrpl4	A	G	9: 21,006,831	Y111C	probably damaging	Het
Mto1	T	C	9: 78,461,517		probably benign	Het
Nalcn	A	T	14: 123,316,126	M972K	possibly damaging	Het
Nemf	T	C	12: 69,346,378	I225V	probably null	Het
Nipal4	T	G	11: 46,150,231	D379A	probably damaging	Het
Nktr	A	G	9: 121,748,866		probably benign	Het
Nlrp5	A	G	7: 23,404,797	T28A	probably benign	Het
Nxph1	T	A	6: 9,247,622	Y198N	probably damaging	Het
Olfr1037	A	T	2: 86,085,720	V19D	probably benign	Het
Olfr1230	T	C	2: 89,296,670	N200S	probably damaging	Het
Olfr1436	T	C	19: 12,298,343	Y263C	probably damaging	Het
P2rx7	A	G	5: 122,673,736	Y370C	probably benign	Het
Piezo1	T	C	8: 122,482,645		probably benign	Het
Piezo1	T	C	8: 122,489,566	D1401G	probably damaging	Het
Plxnd1	A	G	6: 115,969,363	L879P	probably benign	Het
Prex2	G	T	1: 11,162,366	E886*	probably null	Het
Proca1	A	T	11: 78,205,021	I73F	probably damaging	Het
Prss55	A	T	14: 64,079,390	V101E	probably benign	Het
Psg26	T	A	7: 18,478,425	H335L	probably benign	Het
Rai1	A	G	11: 60,185,920	E270G	probably benign	Het
Reep1	A	G	6: 71,780,797	N127D	probably benign	Het
Rims1	G	T	1: 22,428,474	P769Q	probably damaging	Het
Robo4	A	T	9: 37,404,070		probably benign	Het
Ryr2	A	T	13: 11,591,336	D888E	probably benign	Het
Scamp3	A	G	3: 89,180,260	N135D	probably damaging	Het
Sdk2	C	T	11: 113,838,646		silent	Het
Sema4f	A	G	6: 82,918,029	M395T	probably benign	Het
Sgip1	T	C	4: 102,968,337		probably null	Het
Sik2	A	T	9: 50,995,674		probably benign	Het
Smtn	G	T	11: 3,531,326	A223D	possibly damaging	Het
Spen	T	C	4: 141,470,343	T3405A	probably benign	Het
Srebf1	A	G	11: 60,203,486	L601P	probably damaging	Het
Srsf11	A	T	3: 158,031,580		probably benign	Het
Tacc2	T	G	7: 130,624,202	S891R	possibly damaging	Het
Tbc1d17	T	A	7: 44,841,633		probably benign	Het
Tgfbr3l	C	A	8: 4,249,600	R128S	probably damaging	Het
Thsd1	G	A	8: 22,252,318		probably benign	Het
Tlx3	T	C	11: 33,203,072	S130G	probably benign	Het
Tmem25	A	T	9: 44,798,216		probably null	Het
Trak2	A	T	1: 58,946,336	M1K	probably null	Het
Trappc12	C	T	12: 28,746,985	E183K	probably damaging	Het
Ubl3	A	G	5: 148,509,280	V71A	possibly damaging	Het
Unc50	A	G	1: 37,438,799	Y254C	probably damaging	Het
Unkl	T	C	17: 25,229,460		probably null	Het
Uso1	T	A	5: 92,201,192	S819T	probably benign	Het
Yes1	A	T	5: 32,645,051	R103S	probably damaging	Het
Zfp131	A	G	13: 119,767,025	V396A	probably damaging	Het
Zfp553	T	C	7: 127,235,654	I127T	possibly damaging	Het
Zfp599	A	T	9: 22,251,549	N102K	probably benign	Het
Zmynd10	A	T	9: 107,550,037	Q288L	probably benign	Het

Other mutations in Polr2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00987:Polr2a	APN	11	69743794	splice site	probably benign
IGL01067:Polr2a	APN	11	69748014	missense	possibly damaging	0.94
IGL01547:Polr2a	APN	11	69744942	missense	probably damaging	0.99
IGL01589:Polr2a	APN	11	69741194	missense	probably benign
IGL01955:Polr2a	APN	11	69741848	missense	probably damaging	1.00
IGL02457:Polr2a	APN	11	69743250	splice site	probably benign
IGL02526:Polr2a	APN	11	69739467	missense	probably benign	0.03
IGL02792:Polr2a	APN	11	69746112	missense	probably damaging	0.99
IGL03058:Polr2a	APN	11	69745047	splice site	probably null
IGL03083:Polr2a	APN	11	69745046	critical splice acceptor site	probably null
IGL03198:Polr2a	APN	11	69747281	splice site	probably null
IGL03201:Polr2a	APN	11	69745690	nonsense	probably null
Leastest	UTSW	11	69747292	splice site	probably null
PIT4260001:Polr2a	UTSW	11	69735967	missense	possibly damaging	0.93
R0126:Polr2a	UTSW	11	69747425	missense	probably damaging	0.99
R0254:Polr2a	UTSW	11	69743671	missense	possibly damaging	0.75
R0313:Polr2a	UTSW	11	69735080	missense	unknown
R0336:Polr2a	UTSW	11	69736893	missense	possibly damaging	0.92
R0453:Polr2a	UTSW	11	69741019	missense	possibly damaging	0.65
R0762:Polr2a	UTSW	11	69735117	missense	unknown
R1101:Polr2a	UTSW	11	69748071	missense	probably benign	0.23
R1509:Polr2a	UTSW	11	69747213	missense	possibly damaging	0.93
R1547:Polr2a	UTSW	11	69734555	missense	probably benign	0.39
R1567:Polr2a	UTSW	11	69746031	missense	probably benign	0.07
R1597:Polr2a	UTSW	11	69739929	missense	possibly damaging	0.88
R1614:Polr2a	UTSW	11	69743373	missense	possibly damaging	0.75
R1698:Polr2a	UTSW	11	69739877	critical splice donor site	probably null
R1735:Polr2a	UTSW	11	69742396	missense	probably damaging	0.99
R1743:Polr2a	UTSW	11	69739503	missense	probably damaging	0.96
R1900:Polr2a	UTSW	11	69743946	missense	probably damaging	0.99
R1931:Polr2a	UTSW	11	69735375	missense	unknown
R2217:Polr2a	UTSW	11	69742685	critical splice donor site	probably null
R2218:Polr2a	UTSW	11	69742685	critical splice donor site	probably null
R2245:Polr2a	UTSW	11	69735183	missense	unknown
R3123:Polr2a	UTSW	11	69735710	missense	possibly damaging	0.92
R3124:Polr2a	UTSW	11	69735710	missense	possibly damaging	0.92
R4018:Polr2a	UTSW	11	69735059	missense	unknown
R4025:Polr2a	UTSW	11	69743659	missense	possibly damaging	0.95
R4197:Polr2a	UTSW	11	69735336	missense	unknown
R4462:Polr2a	UTSW	11	69746403	missense	probably damaging	1.00
R4508:Polr2a	UTSW	11	69742559	critical splice acceptor site	probably null
R4746:Polr2a	UTSW	11	69735674	missense	probably benign	0.05
R5069:Polr2a	UTSW	11	69736735	splice site	probably null
R5102:Polr2a	UTSW	11	69746945	missense	possibly damaging	0.93
R5195:Polr2a	UTSW	11	69744079	missense	probably damaging	1.00
R5234:Polr2a	UTSW	11	69736840	missense	probably benign	0.03
R5330:Polr2a	UTSW	11	69747275	missense	probably benign	0.01
R5331:Polr2a	UTSW	11	69747275	missense	probably benign	0.01
R5896:Polr2a	UTSW	11	69736260	missense	probably damaging	0.99
R5910:Polr2a	UTSW	11	69746870	missense	probably damaging	0.99
R6128:Polr2a	UTSW	11	69736977	missense	probably damaging	1.00
R6238:Polr2a	UTSW	11	69747221	missense	possibly damaging	0.95
R6244:Polr2a	UTSW	11	69744226	missense	probably damaging	1.00
R6303:Polr2a	UTSW	11	69746913	missense	probably damaging	1.00
R6338:Polr2a	UTSW	11	69739679	splice site	probably null
R6361:Polr2a	UTSW	11	69743337	missense	probably damaging	0.99
R6374:Polr2a	UTSW	11	69736932	missense	probably damaging	0.98
R6630:Polr2a	UTSW	11	69735513	missense	possibly damaging	0.93
R6631:Polr2a	UTSW	11	69735513	missense	possibly damaging	0.93
R6633:Polr2a	UTSW	11	69735513	missense	possibly damaging	0.93
R6897:Polr2a	UTSW	11	69735961	missense	probably benign	0.12
R6923:Polr2a	UTSW	11	69735961	missense	probably benign	0.12
R6933:Polr2a	UTSW	11	69736177	missense	probably damaging	0.99
R6933:Polr2a	UTSW	11	69739467	missense	probably benign	0.03
R6953:Polr2a	UTSW	11	69741711	missense	probably damaging	0.99
R6974:Polr2a	UTSW	11	69747200	missense	probably damaging	0.98
R7033:Polr2a	UTSW	11	69747213	missense	possibly damaging	0.93
R7085:Polr2a	UTSW	11	69743880	missense	probably damaging	0.99
R7112:Polr2a	UTSW	11	69735309	missense	unknown
R7124:Polr2a	UTSW	11	69737462	nonsense	probably null
R7307:Polr2a	UTSW	11	69747292	splice site	probably null
R7319:Polr2a	UTSW	11	69746370	missense	possibly damaging	0.95
R7350:Polr2a	UTSW	11	69741060	missense	possibly damaging	0.92
R7369:Polr2a	UTSW	11	69745977	missense	probably benign	0.01
R7585:Polr2a	UTSW	11	69740002	missense	probably damaging	0.99
R7882:Polr2a	UTSW	11	69736174	missense	possibly damaging	0.86
R7935:Polr2a	UTSW	11	69747504	missense	probably benign	0.00
R8080:Polr2a	UTSW	11	69735048	missense	unknown
R8140:Polr2a	UTSW	11	69746376	missense	probably benign	0.12
R8221:Polr2a	UTSW	11	69737518	missense	probably benign	0.24
R8245:Polr2a	UTSW	11	69739953	missense	probably damaging	0.99
R8274:Polr2a	UTSW	11	69748056	missense	probably damaging	0.99
R8275:Polr2a	UTSW	11	69748056	missense	probably damaging	0.99
R8276:Polr2a	UTSW	11	69748056	missense	probably damaging	0.99
R8277:Polr2a	UTSW	11	69748056	missense	probably damaging	0.99
R8311:Polr2a	UTSW	11	69737456	missense	probably null	0.20
R8477:Polr2a	UTSW	11	69735486	missense	probably benign	0.00
R8677:Polr2a	UTSW	11	69735555	missense	possibly damaging	0.85
R8976:Polr2a	UTSW	11	69747211	missense	possibly damaging	0.92
R9296:Polr2a	UTSW	11	69734736	missense	probably benign	0.39
R9659:Polr2a	UTSW	11	69734828	missense	unknown
R9731:Polr2a	UTSW	11	69747217	missense	possibly damaging	0.88

Predicted Primers

PCR Primer
(F):5'- AGAGGATTTGGAAGCTGGCTATAC -3'
(R):5'- TGGACAGGCAAGCAGATCTTC -3'

Sequencing Primer
(F):5'- ATTTGGAAGCTGGCTATACTGACCC -3'
(R):5'- TCAATTGTATCCGTACCCACAG -3'

Posted On

2014-07-14