Mutagenetix > Incidental Mutation

Incidental Mutation 'R6631:Polr2a'

525152

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

044753-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.968) question?

Stock #

R6631 (G1)

Quality Score

222.009

Status

Validated

Chromosome

Chromosomal Location

69624823-69649459 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 69626339 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 1604 (S1604P)

Ref Sequence

ENSEMBL: ENSMUSP00000050771 (fasta)

Gene Model

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

AlphaFold

P08775

Predicted Effect

possibly damaging
Transcript: ENSMUST00000058470
AA Change: S1604P

PolyPhen 2 Score 0.930 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000050771
Gene: ENSMUSG00000005198
AA Change: S1604P

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 benign
Transcript: ENSMUST00000071213
AA Change: S1566P

PolyPhen 2 Score 0.052 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000071200
Gene: ENSMUSG00000005198
AA Change: S1566P

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: ENSMUST00000120581

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000156588

Meta Mutation Damage Score

0.1795

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.0%
20x: 93.9%

Validation Efficiency

96% (50/52)

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: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931406C07Rik	A	T	9: 15,203,326 (GRCm39)	N159K	probably damaging	Het
Arhgef10l	T	C	4: 140,245,058 (GRCm39)		probably benign	Het
Atosa	A	G	9: 74,861,107 (GRCm39)	D4G	possibly damaging	Het
Avil	A	G	10: 126,843,618 (GRCm39)	S153G	possibly damaging	Het
C2cd3	G	A	7: 100,067,747 (GRCm39)	D877N	probably damaging	Het
Clca3a2	G	A	3: 144,519,405 (GRCm39)	A257V	probably benign	Het
Cramp1	T	A	17: 25,202,931 (GRCm39)	H366L	probably benign	Het
Cyp2c37	C	T	19: 39,998,287 (GRCm39)	S393L	probably damaging	Het
Defb8	T	A	8: 19,495,950 (GRCm39)	I37L	probably benign	Het
Dennd4b	C	A	3: 90,185,039 (GRCm39)		probably null	Het
Eps8l2	G	A	7: 140,936,115 (GRCm39)	R223H	probably damaging	Het
Erbin	A	G	13: 103,961,400 (GRCm39)	L1302P	probably benign	Het
Exoc3l	A	G	8: 106,021,993 (GRCm39)	W37R	probably damaging	Het
Fap	T	C	2: 62,333,725 (GRCm39)	N668S	probably damaging	Het
Gas7	A	G	11: 67,565,107 (GRCm39)	N250S	probably damaging	Het
H2bc12	T	A	13: 22,220,391 (GRCm39)	V112E	probably damaging	Het
Hivep1	C	A	13: 42,309,956 (GRCm39)	P732Q	probably damaging	Het
Irx4	G	T	13: 73,416,545 (GRCm39)	A314S	probably benign	Het
Itgb8	A	T	12: 119,144,712 (GRCm39)	L332*	probably null	Het
Kctd19	A	G	8: 106,111,960 (GRCm39)		probably null	Het
Kif14	G	A	1: 136,443,697 (GRCm39)	S1290N	probably benign	Het
Klk1b3	C	T	7: 43,850,888 (GRCm39)	T140I	probably benign	Het
Lama1	A	G	17: 68,081,477 (GRCm39)	N1305D	probably benign	Het
Lrp1	A	T	10: 127,410,201 (GRCm39)	V1515E	probably damaging	Het
Man2b1	A	G	8: 85,813,440 (GRCm39)		probably null	Het
Mocos	A	G	18: 24,832,988 (GRCm39)	T818A	probably benign	Het
Mpc2	G	T	1: 165,307,081 (GRCm39)	W94L	probably benign	Het
Mrc1	G	A	2: 14,243,296 (GRCm39)	V141I	probably benign	Het
Nalcn	T	C	14: 123,697,663 (GRCm39)	T538A	probably benign	Het
Ndufs3	G	A	2: 90,732,744 (GRCm39)	T114M	probably damaging	Het
Noct	T	C	3: 51,157,621 (GRCm39)	C320R	probably damaging	Het
Or5b117	T	A	19: 13,431,185 (GRCm39)	Q232L	probably benign	Het
Pcdha11	G	T	18: 37,138,844 (GRCm39)	A158S	probably damaging	Het
Pcdhga8	T	A	18: 37,860,109 (GRCm39)	D388E	probably benign	Het
Peg3	T	C	7: 6,712,069 (GRCm39)	E1051G	possibly damaging	Het
Phlda2	T	A	7: 143,055,918 (GRCm39)	I104F	probably damaging	Het
Pomt2	C	T	12: 87,186,417 (GRCm39)		probably null	Het
Ppp6r2	G	A	15: 89,137,458 (GRCm39)		probably null	Het
Prdm2	T	G	4: 142,861,454 (GRCm39)	Q612P	probably benign	Het
Prr5	C	A	15: 84,586,978 (GRCm39)	R243S	probably damaging	Het
Ptgdr2	T	C	19: 10,918,233 (GRCm39)	I250T	probably benign	Het
Rad54l2	A	T	9: 106,590,739 (GRCm39)	C462*	probably null	Het
Sec16a	T	A	2: 26,329,969 (GRCm39)	E682V	probably damaging	Het
Serpina3i	A	G	12: 104,232,725 (GRCm39)	D210G	probably damaging	Het
Slain2	T	A	5: 73,114,748 (GRCm39)	D326E	probably benign	Het
Sned1	A	G	1: 93,209,374 (GRCm39)	E829G	probably damaging	Het
Steap4	G	A	5: 8,026,995 (GRCm39)	W319*	probably null	Het
Taar8c	A	G	10: 23,977,701 (GRCm39)	V37A	probably benign	Het
Tdrd12	T	A	7: 35,184,654 (GRCm39)	Y753F	probably damaging	Het
Tnxb	A	G	17: 34,937,222 (GRCm39)	S3770G	probably damaging	Het
Trrap	A	G	5: 144,708,460 (GRCm39)	N48S	possibly damaging	Het
Zfp558	C	A	9: 18,368,219 (GRCm39)	G190*	probably null	Het

Other mutations in Polr2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00987:Polr2a	APN	11	69,634,620 (GRCm39)	splice site	probably benign
IGL01067:Polr2a	APN	11	69,638,840 (GRCm39)	missense	possibly damaging	0.94
IGL01547:Polr2a	APN	11	69,635,768 (GRCm39)	missense	probably damaging	0.99
IGL01589:Polr2a	APN	11	69,632,020 (GRCm39)	missense	probably benign
IGL01955:Polr2a	APN	11	69,632,674 (GRCm39)	missense	probably damaging	1.00
IGL02457:Polr2a	APN	11	69,634,076 (GRCm39)	splice site	probably benign
IGL02526:Polr2a	APN	11	69,630,293 (GRCm39)	missense	probably benign	0.03
IGL02792:Polr2a	APN	11	69,636,938 (GRCm39)	missense	probably damaging	0.99
IGL03058:Polr2a	APN	11	69,635,873 (GRCm39)	splice site	probably null
IGL03083:Polr2a	APN	11	69,635,872 (GRCm39)	critical splice acceptor site	probably null
IGL03198:Polr2a	APN	11	69,638,107 (GRCm39)	splice site	probably null
IGL03201:Polr2a	APN	11	69,636,516 (GRCm39)	nonsense	probably null
Leastest	UTSW	11	69,638,118 (GRCm39)	splice site	probably null
PIT4260001:Polr2a	UTSW	11	69,626,793 (GRCm39)	missense	possibly damaging	0.93
R0126:Polr2a	UTSW	11	69,638,251 (GRCm39)	missense	probably damaging	0.99
R0254:Polr2a	UTSW	11	69,634,497 (GRCm39)	missense	possibly damaging	0.75
R0313:Polr2a	UTSW	11	69,625,906 (GRCm39)	missense	unknown
R0336:Polr2a	UTSW	11	69,627,719 (GRCm39)	missense	possibly damaging	0.92
R0453:Polr2a	UTSW	11	69,631,845 (GRCm39)	missense	possibly damaging	0.65
R0762:Polr2a	UTSW	11	69,625,943 (GRCm39)	missense	unknown
R1101:Polr2a	UTSW	11	69,638,897 (GRCm39)	missense	probably benign	0.23
R1509:Polr2a	UTSW	11	69,638,039 (GRCm39)	missense	possibly damaging	0.93
R1547:Polr2a	UTSW	11	69,625,381 (GRCm39)	missense	probably benign	0.39
R1567:Polr2a	UTSW	11	69,636,857 (GRCm39)	missense	probably benign	0.07
R1597:Polr2a	UTSW	11	69,630,755 (GRCm39)	missense	possibly damaging	0.88
R1614:Polr2a	UTSW	11	69,634,199 (GRCm39)	missense	possibly damaging	0.75
R1698:Polr2a	UTSW	11	69,630,703 (GRCm39)	critical splice donor site	probably null
R1735:Polr2a	UTSW	11	69,633,222 (GRCm39)	missense	probably damaging	0.99
R1743:Polr2a	UTSW	11	69,630,329 (GRCm39)	missense	probably damaging	0.96
R1899:Polr2a	UTSW	11	69,634,772 (GRCm39)	missense	probably damaging	0.99
R1900:Polr2a	UTSW	11	69,634,772 (GRCm39)	missense	probably damaging	0.99
R1931:Polr2a	UTSW	11	69,626,201 (GRCm39)	missense	unknown
R2217:Polr2a	UTSW	11	69,633,511 (GRCm39)	critical splice donor site	probably null
R2218:Polr2a	UTSW	11	69,633,511 (GRCm39)	critical splice donor site	probably null
R2245:Polr2a	UTSW	11	69,626,009 (GRCm39)	missense	unknown
R3123:Polr2a	UTSW	11	69,626,536 (GRCm39)	missense	possibly damaging	0.92
R3124:Polr2a	UTSW	11	69,626,536 (GRCm39)	missense	possibly damaging	0.92
R4018:Polr2a	UTSW	11	69,625,885 (GRCm39)	missense	unknown
R4025:Polr2a	UTSW	11	69,634,485 (GRCm39)	missense	possibly damaging	0.95
R4197:Polr2a	UTSW	11	69,626,162 (GRCm39)	missense	unknown
R4462:Polr2a	UTSW	11	69,637,229 (GRCm39)	missense	probably damaging	1.00
R4508:Polr2a	UTSW	11	69,633,385 (GRCm39)	critical splice acceptor site	probably null
R4746:Polr2a	UTSW	11	69,626,500 (GRCm39)	missense	probably benign	0.05
R5069:Polr2a	UTSW	11	69,627,561 (GRCm39)	splice site	probably null
R5102:Polr2a	UTSW	11	69,637,771 (GRCm39)	missense	possibly damaging	0.93
R5195:Polr2a	UTSW	11	69,634,905 (GRCm39)	missense	probably damaging	1.00
R5234:Polr2a	UTSW	11	69,627,666 (GRCm39)	missense	probably benign	0.03
R5330:Polr2a	UTSW	11	69,638,101 (GRCm39)	missense	probably benign	0.01
R5331:Polr2a	UTSW	11	69,638,101 (GRCm39)	missense	probably benign	0.01
R5896:Polr2a	UTSW	11	69,627,086 (GRCm39)	missense	probably damaging	0.99
R5910:Polr2a	UTSW	11	69,637,696 (GRCm39)	missense	probably damaging	0.99
R6128:Polr2a	UTSW	11	69,627,803 (GRCm39)	missense	probably damaging	1.00
R6238:Polr2a	UTSW	11	69,638,047 (GRCm39)	missense	possibly damaging	0.95
R6244:Polr2a	UTSW	11	69,635,052 (GRCm39)	missense	probably damaging	1.00
R6303:Polr2a	UTSW	11	69,637,739 (GRCm39)	missense	probably damaging	1.00
R6338:Polr2a	UTSW	11	69,630,505 (GRCm39)	splice site	probably null
R6361:Polr2a	UTSW	11	69,634,163 (GRCm39)	missense	probably damaging	0.99
R6374:Polr2a	UTSW	11	69,627,758 (GRCm39)	missense	probably damaging	0.98
R6630:Polr2a	UTSW	11	69,626,339 (GRCm39)	missense	possibly damaging	0.93
R6633:Polr2a	UTSW	11	69,626,339 (GRCm39)	missense	possibly damaging	0.93
R6897:Polr2a	UTSW	11	69,626,787 (GRCm39)	missense	probably benign	0.12
R6923:Polr2a	UTSW	11	69,626,787 (GRCm39)	missense	probably benign	0.12
R6933:Polr2a	UTSW	11	69,630,293 (GRCm39)	missense	probably benign	0.03
R6933:Polr2a	UTSW	11	69,627,003 (GRCm39)	missense	probably damaging	0.99
R6953:Polr2a	UTSW	11	69,632,537 (GRCm39)	missense	probably damaging	0.99
R6974:Polr2a	UTSW	11	69,638,026 (GRCm39)	missense	probably damaging	0.98
R7033:Polr2a	UTSW	11	69,638,039 (GRCm39)	missense	possibly damaging	0.93
R7085:Polr2a	UTSW	11	69,634,706 (GRCm39)	missense	probably damaging	0.99
R7112:Polr2a	UTSW	11	69,626,135 (GRCm39)	missense	unknown
R7124:Polr2a	UTSW	11	69,628,288 (GRCm39)	nonsense	probably null
R7307:Polr2a	UTSW	11	69,638,118 (GRCm39)	splice site	probably null
R7319:Polr2a	UTSW	11	69,637,196 (GRCm39)	missense	possibly damaging	0.95
R7350:Polr2a	UTSW	11	69,631,886 (GRCm39)	missense	possibly damaging	0.92
R7369:Polr2a	UTSW	11	69,636,803 (GRCm39)	missense	probably benign	0.01
R7585:Polr2a	UTSW	11	69,630,828 (GRCm39)	missense	probably damaging	0.99
R7882:Polr2a	UTSW	11	69,627,000 (GRCm39)	missense	possibly damaging	0.86
R7935:Polr2a	UTSW	11	69,638,330 (GRCm39)	missense	probably benign	0.00
R8080:Polr2a	UTSW	11	69,625,874 (GRCm39)	missense	unknown
R8140:Polr2a	UTSW	11	69,637,202 (GRCm39)	missense	probably benign	0.12
R8221:Polr2a	UTSW	11	69,628,344 (GRCm39)	missense	probably benign	0.24
R8245:Polr2a	UTSW	11	69,630,779 (GRCm39)	missense	probably damaging	0.99
R8274:Polr2a	UTSW	11	69,638,882 (GRCm39)	missense	probably damaging	0.99
R8275:Polr2a	UTSW	11	69,638,882 (GRCm39)	missense	probably damaging	0.99
R8276:Polr2a	UTSW	11	69,638,882 (GRCm39)	missense	probably damaging	0.99
R8277:Polr2a	UTSW	11	69,638,882 (GRCm39)	missense	probably damaging	0.99
R8311:Polr2a	UTSW	11	69,628,282 (GRCm39)	missense	probably null	0.20
R8477:Polr2a	UTSW	11	69,626,312 (GRCm39)	missense	probably benign	0.00
R8677:Polr2a	UTSW	11	69,626,381 (GRCm39)	missense	possibly damaging	0.85
R8976:Polr2a	UTSW	11	69,638,037 (GRCm39)	missense	possibly damaging	0.92
R9296:Polr2a	UTSW	11	69,625,562 (GRCm39)	missense	probably benign	0.39
R9659:Polr2a	UTSW	11	69,625,654 (GRCm39)	missense	unknown
R9731:Polr2a	UTSW	11	69,638,043 (GRCm39)	missense	possibly damaging	0.88

Predicted Primers

PCR Primer
(F):5'- TAGCTAGGTGATGTTGGAGAATAGC -3'
(R):5'- TCCCAGTGCTGCATCTGATG -3'

Sequencing Primer
(F):5'- CTAGGAGAGGTTGGGGAATAGCTTG -3'
(R):5'- AGGTTACTCCCCTGCATGG -3'

Posted On

2018-06-22