Mutagenetix > Incidental Mutation

Incidental Mutation 'R4817:Drosha'

369944

Institutional Source

Beutler Lab

Gene Symbol

Drosha

Ensembl Gene

ENSMUSG00000022191

Gene Name

drosha, ribonuclease type III

Synonyms

Etohi2, 1110013A17Rik, Rnasen

MMRRC Submission

042435-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.963) question?

Stock #

R4817 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

12824901-12935377 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 12914133 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Proline at position 1136 (H1136P)

Ref Sequence

ENSEMBL: ENSMUSP00000129279 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000090292] [ENSMUST00000169061]

AlphaFold

Q5HZJ0

Predicted Effect

possibly damaging
Transcript: ENSMUST00000090292
AA Change: H1136P

PolyPhen 2 Score 0.674 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000087762
Gene: ENSMUSG00000022191
AA Change: H1136P

Domain	Start	End	E-Value	Type
low complexity region	13	32	N/A	INTRINSIC
low complexity region	43	69	N/A	INTRINSIC
low complexity region	72	102	N/A	INTRINSIC
low complexity region	109	137	N/A	INTRINSIC
low complexity region	142	169	N/A	INTRINSIC
low complexity region	185	200	N/A	INTRINSIC
low complexity region	227	269	N/A	INTRINSIC
low complexity region	273	301	N/A	INTRINSIC
low complexity region	357	370	N/A	INTRINSIC
low complexity region	387	410	N/A	INTRINSIC
low complexity region	472	499	N/A	INTRINSIC
SCOP:d1jfza_	878	902	4e-4	SMART
RIBOc	942	1076	1.73e-45	SMART
Blast:RIBOc	1086	1112	1e-6	BLAST
RIBOc	1121	1253	1.6e-49	SMART
DSRM	1260	1332	5.75e-20	SMART
coiled coil region	1346	1370	N/A	INTRINSIC

Predicted Effect

SMART Domains

Protein: ENSMUSP00000121499
Gene: ENSMUSG00000022191
AA Change: H778P

Domain	Start	End	E-Value	Type
low complexity region	115	142	N/A	INTRINSIC
SCOP:d1jfza_	521	545	6e-4	SMART
RIBOc	585	719	1.73e-45	SMART
Blast:RIBOc	729	755	1e-6	BLAST
RIBOc	764	896	1.6e-49	SMART
DSRM	903	975	5.75e-20	SMART
coiled coil region	988	1012	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000169061
AA Change: H1136P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000129279
Gene: ENSMUSG00000022191
AA Change: H1136P

Domain	Start	End	E-Value	Type
low complexity region	13	32	N/A	INTRINSIC
low complexity region	43	69	N/A	INTRINSIC
low complexity region	72	102	N/A	INTRINSIC
low complexity region	109	137	N/A	INTRINSIC
low complexity region	142	169	N/A	INTRINSIC
low complexity region	185	200	N/A	INTRINSIC
low complexity region	227	269	N/A	INTRINSIC
low complexity region	273	301	N/A	INTRINSIC
low complexity region	357	370	N/A	INTRINSIC
low complexity region	387	410	N/A	INTRINSIC
low complexity region	472	499	N/A	INTRINSIC
SCOP:d1jfza_	878	902	4e-4	SMART
RIBOc	942	1076	1.73e-45	SMART
Blast:RIBOc	1086	1112	1e-6	BLAST
RIBOc	1121	1253	1.6e-49	SMART
DSRM	1260	1332	5.75e-20	SMART
coiled coil region	1346	1370	N/A	INTRINSIC

Meta Mutation Damage Score

0.2711

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.8%
20x: 94.0%

Validation Efficiency

96% (108/112)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]
PHENOTYPE: Mice heterozygous for a knock-out allele and a conditional allele activated in the immune system exhibit increased inflammation in multiple systems, cachexia and premature death. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 97 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acp2	T	A	2: 91,033,963 (GRCm39)	D44E	probably damaging	Het
Acp5	T	C	9: 22,038,379 (GRCm39)	I307M	probably benign	Het
Ahsa1	A	G	12: 87,319,940 (GRCm39)	D245G	possibly damaging	Het
Ankrd40	A	G	11: 94,230,459 (GRCm39)	K316E	probably benign	Het
Apol9b	G	A	15: 77,620,088 (GRCm39)	E295K	possibly damaging	Het
Aqp4	C	A	18: 15,532,815 (GRCm39)	G93C	probably damaging	Het
Arhgap21	A	G	2: 20,854,967 (GRCm39)	V1465A	probably benign	Het
Arhgap5	C	T	12: 52,565,992 (GRCm39)	P988S	possibly damaging	Het
Asxl3	A	C	18: 22,658,511 (GRCm39)	K2174Q	probably damaging	Het
Brf1	A	T	12: 112,935,921 (GRCm39)	I250N	probably damaging	Het
Calm1	A	G	12: 100,169,832 (GRCm39)		probably null	Het
Ccdc33	C	T	9: 57,974,818 (GRCm39)	V352M	probably damaging	Het
Ccdc88a	G	T	11: 29,410,907 (GRCm39)	K464N	probably benign	Het
Cdadc1	AGACGGA	AGA	14: 59,806,440 (GRCm39)		probably null	Het
Cdc25b	T	A	2: 131,035,223 (GRCm39)	I327N	probably damaging	Het
Cenpf	G	A	1: 189,414,566 (GRCm39)	H184Y	possibly damaging	Het
Cimap1d	G	A	10: 79,475,851 (GRCm39)	P238S	probably damaging	Het
Col6a5	G	A	9: 105,811,497 (GRCm39)	T674I	unknown	Het
Creg2	A	T	1: 39,662,358 (GRCm39)	M258K	probably damaging	Het
Csf3r	T	A	4: 125,931,449 (GRCm39)	Y477*	probably null	Het
Cyp3a44	T	A	5: 145,740,565 (GRCm39)	Y25F	possibly damaging	Het
Degs2	T	A	12: 108,655,325 (GRCm39)	R283*	probably null	Het
Dido1	T	C	2: 180,303,209 (GRCm39)	N1565S	probably benign	Het
Dnah6	A	T	6: 72,999,407 (GRCm39)	M4008K	probably benign	Het
Dnmbp	C	A	19: 43,838,411 (GRCm39)	G1138V	probably benign	Het
Duox2	T	G	2: 122,126,996 (GRCm39)	N173T	probably damaging	Het
Dync1li1	T	G	9: 114,534,162 (GRCm39)	I87M	probably benign	Het
E2f8	A	C	7: 48,517,494 (GRCm39)	S770A	probably benign	Het
Efemp1	A	G	11: 28,876,241 (GRCm39)	T469A	probably damaging	Het
Eif3f	A	T	7: 108,536,982 (GRCm39)	T136S	probably damaging	Het
Enpp5	T	C	17: 44,391,871 (GRCm39)	*46R	probably null	Het
Epb41l4b	A	G	4: 57,103,428 (GRCm39)	V136A	probably damaging	Het
Fam186a	A	C	15: 99,831,419 (GRCm39)		probably benign	Het
Flt4	A	G	11: 49,516,242 (GRCm39)	Y115C	probably damaging	Het
Gal	T	A	19: 3,461,126 (GRCm39)		probably null	Het
Galnt3	C	T	2: 65,923,883 (GRCm39)	V462I	possibly damaging	Het
Gas2l1	A	G	11: 5,011,429 (GRCm39)	S467P	possibly damaging	Het
Gbx1	A	G	5: 24,731,204 (GRCm39)	L204P	probably damaging	Het
Gle1	T	A	2: 29,826,223 (GRCm39)	S101T	probably benign	Het
Gltpd2	A	C	11: 70,410,303 (GRCm39)	Q87P	probably damaging	Het
Gm12789	T	A	4: 101,846,079 (GRCm39)	D113E	probably damaging	Het
Grin3b	G	A	10: 79,812,732 (GRCm39)	G936R	probably benign	Het
Gtf3c2	C	T	5: 31,331,434 (GRCm39)		probably null	Het
Gvin3	T	A	7: 106,200,437 (GRCm39)		noncoding transcript	Het
Klhl28	T	C	12: 65,004,043 (GRCm39)	T157A	probably benign	Het
Kmt2a	A	G	9: 44,732,763 (GRCm39)		probably benign	Het
Lamp1	A	G	8: 13,222,541 (GRCm39)	T242A	probably benign	Het
Lhfpl5	T	G	17: 28,795,300 (GRCm39)	I109S	possibly damaging	Het
Lhfpl5	T	A	17: 28,801,962 (GRCm39)	*220R	probably null	Het
Map4k2	C	T	19: 6,394,459 (GRCm39)	T313I	probably damaging	Het
Matn2	A	G	15: 34,423,945 (GRCm39)	D601G	probably damaging	Het
Mcur1	C	T	13: 43,705,147 (GRCm39)	V170M	possibly damaging	Het
Mphosph10	T	C	7: 64,041,969 (GRCm39)		probably benign	Het
Nat8l	G	A	5: 34,158,387 (GRCm39)	A266T	probably benign	Het
Nckap5	G	T	1: 125,954,952 (GRCm39)	D469E	possibly damaging	Het
Nckap5l	G	T	15: 99,321,067 (GRCm39)	P1238T	probably damaging	Het
Ngf	A	G	3: 102,417,156 (GRCm39)		probably benign	Het
Ntng1	T	A	3: 109,842,184 (GRCm39)	L196F	probably damaging	Het
Or2q1	A	G	6: 42,794,896 (GRCm39)	I164V	possibly damaging	Het
Or2v2	A	T	11: 49,004,448 (GRCm39)	V35D	probably damaging	Het
Pclo	A	T	5: 14,725,045 (GRCm39)	Y1301F	unknown	Het
Pclo	A	G	5: 14,763,139 (GRCm39)	T3871A	unknown	Het
Peli3	T	C	19: 4,982,594 (GRCm39)	E357G	probably damaging	Het
Pkd1	T	A	17: 24,784,348 (GRCm39)		probably null	Het
Pla2g2c	T	G	4: 138,461,645 (GRCm39)	F38C	probably damaging	Het
Plekha2	T	A	8: 25,549,960 (GRCm39)	T126S	possibly damaging	Het
Polr3f	T	A	2: 144,376,001 (GRCm39)	*142K	probably null	Het
Ppcs	C	T	4: 119,276,343 (GRCm39)	V81M	probably benign	Het
Prl7a1	A	G	13: 27,819,747 (GRCm39)	I169T	probably damaging	Het
Rbm19	C	A	5: 120,271,799 (GRCm39)		probably benign	Het
Rdh7	T	A	10: 127,721,631 (GRCm39)	Y215F	probably benign	Het
Rragd	T	G	4: 32,995,072 (GRCm39)	S62R	probably benign	Het
Rtel1	T	C	2: 180,997,728 (GRCm39)	S1114P	possibly damaging	Het
Serpinb5	G	T	1: 106,800,069 (GRCm39)	L86F	probably damaging	Het
Setbp1	A	G	18: 78,902,015 (GRCm39)	S551P	probably damaging	Het
Setd6	T	C	8: 96,443,683 (GRCm39)		probably benign	Het
Slmap	A	C	14: 26,183,507 (GRCm39)	M292R	probably damaging	Het
Srrm4	T	C	5: 116,615,193 (GRCm39)	D97G	unknown	Het
Stk-ps2	G	A	1: 46,068,125 (GRCm39)		noncoding transcript	Het
Syce1	A	T	7: 140,358,336 (GRCm39)	M204K	probably benign	Het
Syk	A	G	13: 52,765,242 (GRCm39)	K123R	probably benign	Het
Tbc1d14	A	T	5: 36,729,175 (GRCm39)	S64T	probably damaging	Het
Tmt1a3	A	T	15: 100,233,214 (GRCm39)	D135V	probably damaging	Het
Traf3ip3	T	C	1: 192,867,137 (GRCm39)	K295E	probably damaging	Het
Trp53bp2	T	C	1: 182,269,370 (GRCm39)		probably null	Het
Tsc2	T	A	17: 24,815,716 (GRCm39)		probably null	Het
Tspyl4	T	A	10: 34,173,734 (GRCm39)	C75*	probably null	Het
Uqcc2	T	C	17: 27,344,133 (GRCm39)	I52V	probably benign	Het
Vcp	T	A	4: 42,983,486 (GRCm39)	T525S	probably damaging	Het
Vmn2r18	A	T	5: 151,508,897 (GRCm39)		probably null	Het
Vmp1	A	G	11: 86,492,879 (GRCm39)	V310A	probably benign	Het
Vps13d	T	A	4: 144,795,735 (GRCm39)	R3671S	probably damaging	Het
Wdr3	T	C	3: 100,053,861 (GRCm39)	T544A	possibly damaging	Het
Zc3h14	C	G	12: 98,719,107 (GRCm39)	D157E	probably damaging	Het
Zfp541	T	A	7: 15,824,307 (GRCm39)	F1010I	probably damaging	Het
Zfp64	T	C	2: 168,768,032 (GRCm39)	T527A	probably benign	Het
Zyx	G	T	6: 42,333,421 (GRCm39)	R449M	probably damaging	Het

Other mutations in Drosha

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00576:Drosha	APN	15	12,883,280 (GRCm39)	missense	probably damaging	0.99
IGL00736:Drosha	APN	15	12,834,045 (GRCm39)	missense	unknown
IGL00963:Drosha	APN	15	12,926,083 (GRCm39)	missense	probably damaging	0.99
IGL01010:Drosha	APN	15	12,827,375 (GRCm39)	unclassified	probably benign
IGL01340:Drosha	APN	15	12,834,109 (GRCm39)	intron	probably benign
IGL01481:Drosha	APN	15	12,842,525 (GRCm39)	missense	probably benign
IGL01714:Drosha	APN	15	12,878,870 (GRCm39)	missense	probably damaging	1.00
IGL01721:Drosha	APN	15	12,846,198 (GRCm39)	nonsense	probably null
IGL01765:Drosha	APN	15	12,902,766 (GRCm39)	missense	probably damaging	1.00
IGL01893:Drosha	APN	15	12,866,736 (GRCm39)	splice site	probably benign
IGL01944:Drosha	APN	15	12,889,805 (GRCm39)	missense	probably damaging	1.00
IGL02285:Drosha	APN	15	12,833,950 (GRCm39)	missense	unknown
IGL02970:Drosha	APN	15	12,914,042 (GRCm39)	missense	probably damaging	0.98
IGL02990:Drosha	APN	15	12,827,353 (GRCm39)	unclassified	probably benign
IGL03019:Drosha	APN	15	12,846,185 (GRCm39)	missense	probably damaging	1.00
IGL03279:Drosha	APN	15	12,859,478 (GRCm39)	missense	probably benign	0.03
IGL03390:Drosha	APN	15	12,885,069 (GRCm39)	splice site	probably null
tippicanoe	UTSW	15	12,859,551 (GRCm39)	splice site	probably null
Tyler	UTSW	15	12,861,792 (GRCm39)	missense	probably benign	0.45
R0115:Drosha	UTSW	15	12,846,216 (GRCm39)	missense	probably benign	0.15
R0352:Drosha	UTSW	15	12,837,374 (GRCm39)	missense	unknown
R0401:Drosha	UTSW	15	12,926,117 (GRCm39)	nonsense	probably null
R0541:Drosha	UTSW	15	12,907,474 (GRCm39)	missense	probably benign	0.09
R0784:Drosha	UTSW	15	12,867,764 (GRCm39)	splice site	probably benign
R0918:Drosha	UTSW	15	12,842,619 (GRCm39)	critical splice donor site	probably null
R1473:Drosha	UTSW	15	12,912,606 (GRCm39)	missense	probably benign	0.04
R1503:Drosha	UTSW	15	12,848,159 (GRCm39)	missense	probably benign	0.02
R1526:Drosha	UTSW	15	12,914,070 (GRCm39)	missense	probably damaging	1.00
R1809:Drosha	UTSW	15	12,890,198 (GRCm39)	missense	probably null	1.00
R1859:Drosha	UTSW	15	12,878,804 (GRCm39)	missense	probably benign	0.14
R2004:Drosha	UTSW	15	12,915,467 (GRCm39)	missense	probably damaging	0.98
R2060:Drosha	UTSW	15	12,924,245 (GRCm39)	missense	possibly damaging	0.94
R2516:Drosha	UTSW	15	12,859,551 (GRCm39)	splice site	probably null
R3691:Drosha	UTSW	15	12,834,724 (GRCm39)	missense	unknown
R3784:Drosha	UTSW	15	12,890,615 (GRCm39)	missense	possibly damaging	0.82
R3789:Drosha	UTSW	15	12,912,623 (GRCm39)	nonsense	probably null
R3790:Drosha	UTSW	15	12,912,623 (GRCm39)	nonsense	probably null
R4020:Drosha	UTSW	15	12,837,422 (GRCm39)	missense	possibly damaging	0.96
R4989:Drosha	UTSW	15	12,935,093 (GRCm39)	missense	probably benign	0.05
R5080:Drosha	UTSW	15	12,842,229 (GRCm39)	missense	probably benign	0.01
R5132:Drosha	UTSW	15	12,837,377 (GRCm39)	missense	unknown
R5215:Drosha	UTSW	15	12,885,219 (GRCm39)	intron	probably benign
R5386:Drosha	UTSW	15	12,842,207 (GRCm39)	missense	probably benign
R5457:Drosha	UTSW	15	12,926,115 (GRCm39)	missense	probably benign	0.26
R5536:Drosha	UTSW	15	12,929,797 (GRCm39)	missense	possibly damaging	0.58
R5800:Drosha	UTSW	15	12,902,733 (GRCm39)	missense	probably damaging	1.00
R5800:Drosha	UTSW	15	12,865,153 (GRCm39)	missense	probably damaging	1.00
R5915:Drosha	UTSW	15	12,935,152 (GRCm39)	missense	probably damaging	0.97
R5988:Drosha	UTSW	15	12,834,582 (GRCm39)	intron	probably benign
R6033:Drosha	UTSW	15	12,926,085 (GRCm39)	missense	probably benign	0.25
R6033:Drosha	UTSW	15	12,926,085 (GRCm39)	missense	probably benign	0.25
R6063:Drosha	UTSW	15	12,834,156 (GRCm39)	intron	probably benign
R6391:Drosha	UTSW	15	12,889,803 (GRCm39)	nonsense	probably null
R6492:Drosha	UTSW	15	12,861,792 (GRCm39)	missense	probably benign	0.45
R6799:Drosha	UTSW	15	12,912,623 (GRCm39)	nonsense	probably null
R6870:Drosha	UTSW	15	12,907,479 (GRCm39)	missense	probably benign	0.17
R6920:Drosha	UTSW	15	12,834,396 (GRCm39)	missense	unknown
R7101:Drosha	UTSW	15	12,865,153 (GRCm39)	missense	probably damaging	1.00
R7142:Drosha	UTSW	15	12,924,232 (GRCm39)	missense	possibly damaging	0.70
R7275:Drosha	UTSW	15	12,846,169 (GRCm39)	missense	possibly damaging	0.73
R7337:Drosha	UTSW	15	12,846,285 (GRCm39)	missense	possibly damaging	0.80
R7471:Drosha	UTSW	15	12,889,742 (GRCm39)	missense	probably damaging	1.00
R7538:Drosha	UTSW	15	12,926,329 (GRCm39)	missense	probably damaging	1.00
R7559:Drosha	UTSW	15	12,842,508 (GRCm39)	missense	probably damaging	0.96
R7651:Drosha	UTSW	15	12,859,522 (GRCm39)	missense	probably benign	0.30
R7652:Drosha	UTSW	15	12,859,522 (GRCm39)	missense	probably benign	0.30
R7653:Drosha	UTSW	15	12,859,522 (GRCm39)	missense	probably benign	0.30
R7727:Drosha	UTSW	15	12,881,731 (GRCm39)	missense	probably damaging	1.00
R7780:Drosha	UTSW	15	12,848,172 (GRCm39)	missense	probably benign	0.01
R8068:Drosha	UTSW	15	12,883,276 (GRCm39)	nonsense	probably null
R8283:Drosha	UTSW	15	12,890,587 (GRCm39)	missense	possibly damaging	0.47
R8523:Drosha	UTSW	15	12,834,408 (GRCm39)	missense	unknown
R8985:Drosha	UTSW	15	12,924,187 (GRCm39)	missense	possibly damaging	0.66
R9418:Drosha	UTSW	15	12,885,167 (GRCm39)	missense	probably benign	0.02
R9501:Drosha	UTSW	15	12,928,992 (GRCm39)	missense	probably damaging	1.00
R9674:Drosha	UTSW	15	12,890,170 (GRCm39)	missense	probably damaging	1.00
Z1177:Drosha	UTSW	15	12,842,178 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- ATTTCTGCCCACAGGAGATG -3'
(R):5'- GGACAGACAACAGTCCCTGATC -3'

Sequencing Primer
(F):5'- TGCCCACAGGAGATGGAATTTTATAG -3'
(R):5'- GATCCACACTACTGCCTGG -3'

Posted On

2016-02-04