Mutagenetix > Incidental Mutation

Incidental Mutation 'R5259:Depdc5'

401293

Institutional Source

Beutler Lab

Gene Symbol

Depdc5

Ensembl Gene

ENSMUSG00000037426

Gene Name

DEP domain containing 5

Synonyms

MMRRC Submission

042856-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5259 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

33021045-33151580 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 33095635 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Leucine at position 824 (P824L)

Ref Sequence

ENSEMBL: ENSMUSP00000113980 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049780] [ENSMUST00000087897] [ENSMUST00000119705] [ENSMUST00000120902] [ENSMUST00000124780]

AlphaFold

P61460

Predicted Effect

probably benign
Transcript: ENSMUST00000049780
AA Change: P824L

PolyPhen 2 Score 0.068 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000052807
Gene: ENSMUSG00000037426
AA Change: P824L

Domain	Start	End	E-Value	Type
Pfam:DUF3608	100	382	3.7e-64	PFAM
low complexity region	491	508	N/A	INTRINSIC
low complexity region	656	667	N/A	INTRINSIC
low complexity region	690	699	N/A	INTRINSIC
low complexity region	817	827	N/A	INTRINSIC
low complexity region	985	997	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000087897
AA Change: P833L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000085207
Gene: ENSMUSG00000037426
AA Change: P833L

Domain	Start	End	E-Value	Type
Pfam:DUF3608	100	382	2.3e-63	PFAM
low complexity region	491	508	N/A	INTRINSIC
low complexity region	656	667	N/A	INTRINSIC
low complexity region	690	699	N/A	INTRINSIC
low complexity region	826	836	N/A	INTRINSIC
low complexity region	994	1006	N/A	INTRINSIC
low complexity region	1159	1175	N/A	INTRINSIC
DEP	1184	1259	2.49e-15	SMART
low complexity region	1322	1335	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000119705
AA Change: P824L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113862
Gene: ENSMUSG00000037426
AA Change: P824L

Domain	Start	End	E-Value	Type
Pfam:DUF3608	100	382	3e-117	PFAM
low complexity region	491	508	N/A	INTRINSIC
low complexity region	656	667	N/A	INTRINSIC
low complexity region	690	699	N/A	INTRINSIC
low complexity region	817	827	N/A	INTRINSIC
low complexity region	985	997	N/A	INTRINSIC
low complexity region	1150	1166	N/A	INTRINSIC
DEP	1175	1250	2.49e-15	SMART
low complexity region	1313	1326	N/A	INTRINSIC
low complexity region	1511	1525	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000120902
AA Change: P824L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113980
Gene: ENSMUSG00000037426
AA Change: P824L

Domain	Start	End	E-Value	Type
Pfam:DUF3608	100	382	3.7e-63	PFAM
low complexity region	491	508	N/A	INTRINSIC
low complexity region	656	667	N/A	INTRINSIC
low complexity region	690	699	N/A	INTRINSIC
low complexity region	817	827	N/A	INTRINSIC
low complexity region	985	997	N/A	INTRINSIC
low complexity region	1128	1144	N/A	INTRINSIC
DEP	1153	1228	2.49e-15	SMART
low complexity region	1291	1304	N/A	INTRINSIC
low complexity region	1489	1503	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000124780
AA Change: P186L

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000120120
Gene: ENSMUSG00000037426
AA Change: P186L

Domain	Start	End	E-Value	Type
low complexity region	179	189	N/A	INTRINSIC
low complexity region	347	359	N/A	INTRINSIC
SCOP:d1fsha_	519	586	1e-13	SMART
Blast:DEP	537	589	2e-24	BLAST

Predicted Effect

unknown
Transcript: ENSMUST00000137169
AA Change: P230L

SMART Domains

Protein: ENSMUSP00000121089
Gene: ENSMUSG00000037426
AA Change: P230L

Domain	Start	End	E-Value	Type
low complexity region	54	65	N/A	INTRINSIC
low complexity region	88	97	N/A	INTRINSIC
low complexity region	224	234	N/A	INTRINSIC
low complexity region	392	404	N/A	INTRINSIC
low complexity region	535	551	N/A	INTRINSIC
DEP	560	635	2.49e-15	SMART
low complexity region	698	711	N/A	INTRINSIC
low complexity region	896	910	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000201802

Meta Mutation Damage Score

0.1985

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.7%

Validation Efficiency

100% (68/68)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit preweaning lethality. Mice homozygous for a conditional allele activated in neurons exhibit reduced body weight, limb grasping, premature death, spontaneous seizure, increased brain size due to neuron hypertrophy and increased PTZ seizure susceptibility. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abhd18	A	C	3: 40,871,325 (GRCm39)	T50P	probably damaging	Het
Adam5	T	A	8: 25,300,850 (GRCm39)	L226F	possibly damaging	Het
Adi1	T	C	12: 28,725,544 (GRCm39)		probably benign	Het
Apc	T	C	18: 34,447,343 (GRCm39)	V1379A	probably benign	Het
Atp13a4	G	A	16: 29,275,428 (GRCm39)	T352M	probably damaging	Het
Baat	T	A	4: 49,490,070 (GRCm39)	N338I	probably benign	Het
Bdnf	A	G	2: 109,554,327 (GRCm39)	T234A	probably benign	Het
Catsperd	A	C	17: 56,967,235 (GRCm39)	T539P	possibly damaging	Het
Cd109	A	T	9: 78,617,434 (GRCm39)	T1311S	probably benign	Het
Ceacam18	T	C	7: 43,286,536 (GRCm39)		probably null	Het
Cfap96	T	C	8: 46,415,373 (GRCm39)	E211G	probably benign	Het
Cfhr4	C	T	1: 139,668,233 (GRCm39)	C300Y	probably damaging	Het
Chsy3	T	A	18: 59,543,318 (GRCm39)	S819T	probably damaging	Het
Col4a4	G	T	1: 82,431,614 (GRCm39)	R1557S	unknown	Het
Ddx18	A	G	1: 121,495,518 (GRCm39)		probably null	Het
Fam13c	C	G	10: 70,276,893 (GRCm39)	A17G	probably benign	Het
Fermt1	T	C	2: 132,748,685 (GRCm39)	Y646C	probably damaging	Het
Fra10ac1	A	G	19: 38,188,110 (GRCm39)	S229P	probably benign	Het
Gbp8	A	T	5: 105,198,845 (GRCm39)	H23Q	probably benign	Het
Gdf2	T	C	14: 33,666,788 (GRCm39)	V170A	probably benign	Het
Gm15723	T	C	10: 114,652,722 (GRCm39)		noncoding transcript	Het
Gm815	G	A	19: 26,863,806 (GRCm39)	V16I	unknown	Het
Ighv1-75	T	A	12: 115,797,797 (GRCm39)	K42*	probably null	Het
Isx	A	G	8: 75,619,473 (GRCm39)	T222A	probably benign	Het
Itgax	G	A	7: 127,747,450 (GRCm39)	D1018N	probably damaging	Het
Kcnc4	A	G	3: 107,355,401 (GRCm39)	F349S	probably damaging	Het
Lama3	A	C	18: 12,598,565 (GRCm39)	S991R	probably damaging	Het
Larp4b	C	T	13: 9,208,220 (GRCm39)	A398V	probably damaging	Het
Ltbp1	A	G	17: 75,670,357 (GRCm39)	N1466S	probably benign	Het
Metrn	A	T	17: 26,015,514 (GRCm39)	L67Q	probably damaging	Het
Morc1	G	A	16: 48,451,132 (GRCm39)	R937Q	probably benign	Het
Mta3	A	G	17: 84,112,003 (GRCm39)	Y577C	probably damaging	Het
Nalcn	A	G	14: 123,753,063 (GRCm39)	F308L	possibly damaging	Het
Nat8	A	T	6: 85,807,873 (GRCm39)	S87T	probably benign	Het
Oplah	A	T	15: 76,185,410 (GRCm39)		probably null	Het
Or2ak6	A	G	11: 58,592,778 (GRCm39)	N84D	probably benign	Het
Or2ak6	A	C	11: 58,592,779 (GRCm39)	N84T	possibly damaging	Het
Or7e166	A	G	9: 19,624,109 (GRCm39)		probably null	Het
Pcdh15	A	T	10: 74,232,204 (GRCm39)	I668L	possibly damaging	Het
Pecr	A	G	1: 72,316,444 (GRCm39)		probably null	Het
Plxna4	T	C	6: 32,493,956 (GRCm39)	E220G	possibly damaging	Het
Pnma8b	A	G	7: 16,679,199 (GRCm39)	K61R	unknown	Het
Prl8a6	C	T	13: 27,620,179 (GRCm39)	W81*	probably null	Het
Rab33b	C	T	3: 51,392,033 (GRCm39)		probably benign	Het
Rbm33	T	A	5: 28,557,772 (GRCm39)		probably null	Het
Relch	A	G	1: 105,649,101 (GRCm39)	S747G	probably benign	Het
Reln	C	T	5: 22,308,395 (GRCm39)	V325M	possibly damaging	Het
Rheb	A	C	5: 25,008,743 (GRCm39)	D158E	probably benign	Het
Rhebl1	T	A	15: 98,778,464 (GRCm39)		probably benign	Het
Rmdn2	T	A	17: 79,975,446 (GRCm39)	Y312N	probably damaging	Het
Scamp1	T	G	13: 94,368,594 (GRCm39)	N58T	probably benign	Het
Semp2l1	A	T	1: 32,584,598 (GRCm39)	C437*	probably null	Het
Slc35a1	C	T	4: 34,683,322 (GRCm39)	V53M	probably benign	Het
Slc35f3	A	T	8: 127,115,872 (GRCm39)	L266F	probably damaging	Het
Slc45a2	C	T	15: 11,027,871 (GRCm39)	T480I	probably damaging	Het
Ticrr	T	A	7: 79,344,471 (GRCm39)	S1445R	probably benign	Het
Ttc23l	T	C	15: 10,515,236 (GRCm39)	N381D	probably damaging	Het
Usp17ld	T	A	7: 102,899,781 (GRCm39)	K384*	probably null	Het
Vmn1r20	T	A	6: 57,409,050 (GRCm39)	Y125*	probably null	Het
Zfp738	G	T	13: 67,817,805 (GRCm39)	Q729K	probably benign	Het
Zfp770	T	A	2: 114,027,674 (GRCm39)	M132L	probably benign	Het

Other mutations in Depdc5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00861:Depdc5	APN	5	33,125,158 (GRCm39)	splice site	probably null
IGL01019:Depdc5	APN	5	33,050,745 (GRCm39)	missense	probably damaging	0.96
IGL01067:Depdc5	APN	5	33,056,411 (GRCm39)	splice site	probably null
IGL01405:Depdc5	APN	5	33,095,033 (GRCm39)	missense	possibly damaging	0.90
IGL01577:Depdc5	APN	5	33,113,241 (GRCm39)	missense	possibly damaging	0.49
IGL01633:Depdc5	APN	5	33,081,544 (GRCm39)	missense	probably damaging	1.00
IGL01998:Depdc5	APN	5	33,102,495 (GRCm39)	splice site	probably benign
IGL02025:Depdc5	APN	5	33,103,976 (GRCm39)	critical splice acceptor site	probably null
IGL02167:Depdc5	APN	5	33,061,145 (GRCm39)	missense	probably damaging	1.00
IGL02537:Depdc5	APN	5	33,125,131 (GRCm39)	missense	probably damaging	1.00
IGL02812:Depdc5	APN	5	33,050,712 (GRCm39)	splice site	probably benign
IGL03001:Depdc5	APN	5	33,102,434 (GRCm39)	missense	possibly damaging	0.74
IGL03253:Depdc5	APN	5	33,026,157 (GRCm39)	unclassified	probably benign
alligator	UTSW	5	33,121,851 (GRCm39)	splice site	probably null
lagarto	UTSW	5	33,136,852 (GRCm39)	missense	probably damaging	1.00
sauros	UTSW	5	33,144,310 (GRCm39)	missense	possibly damaging	0.92
IGL02988:Depdc5	UTSW	5	33,113,511 (GRCm39)	splice site	probably null
R0038:Depdc5	UTSW	5	33,026,197 (GRCm39)	missense	probably benign	0.01
R0038:Depdc5	UTSW	5	33,026,197 (GRCm39)	missense	probably benign	0.01
R0153:Depdc5	UTSW	5	33,091,281 (GRCm39)	splice site	probably benign
R0179:Depdc5	UTSW	5	33,058,918 (GRCm39)	unclassified	probably benign
R0212:Depdc5	UTSW	5	33,069,586 (GRCm39)	missense	probably benign	0.00
R0239:Depdc5	UTSW	5	33,100,584 (GRCm39)	missense	probably damaging	1.00
R0239:Depdc5	UTSW	5	33,100,584 (GRCm39)	missense	probably damaging	1.00
R0302:Depdc5	UTSW	5	33,061,890 (GRCm39)	critical splice donor site	probably benign
R0511:Depdc5	UTSW	5	33,102,372 (GRCm39)	nonsense	probably null
R0677:Depdc5	UTSW	5	33,058,814 (GRCm39)	missense	probably damaging	1.00
R0884:Depdc5	UTSW	5	33,075,322 (GRCm39)	missense	possibly damaging	0.94
R0973:Depdc5	UTSW	5	33,144,310 (GRCm39)	missense	possibly damaging	0.92
R1314:Depdc5	UTSW	5	33,034,418 (GRCm39)	missense	probably damaging	1.00
R1611:Depdc5	UTSW	5	33,148,297 (GRCm39)	missense	probably damaging	1.00
R1687:Depdc5	UTSW	5	33,067,751 (GRCm39)	critical splice acceptor site	probably benign
R1748:Depdc5	UTSW	5	33,075,286 (GRCm39)	missense	probably benign	0.24
R1903:Depdc5	UTSW	5	33,067,751 (GRCm39)	critical splice acceptor site	probably benign
R1956:Depdc5	UTSW	5	33,061,175 (GRCm39)	missense	probably damaging	1.00
R1997:Depdc5	UTSW	5	33,059,250 (GRCm39)	critical splice donor site	probably null
R2079:Depdc5	UTSW	5	33,104,018 (GRCm39)	missense	possibly damaging	0.75
R2131:Depdc5	UTSW	5	33,148,125 (GRCm39)	nonsense	probably null
R2291:Depdc5	UTSW	5	33,136,746 (GRCm39)	missense	probably damaging	1.00
R2422:Depdc5	UTSW	5	33,148,379 (GRCm39)	missense	probably damaging	1.00
R2851:Depdc5	UTSW	5	33,081,515 (GRCm39)	missense	probably damaging	0.96
R2852:Depdc5	UTSW	5	33,081,515 (GRCm39)	missense	probably damaging	0.96
R2937:Depdc5	UTSW	5	33,058,965 (GRCm39)	splice site	probably null
R2938:Depdc5	UTSW	5	33,058,965 (GRCm39)	splice site	probably null
R2974:Depdc5	UTSW	5	33,091,361 (GRCm39)	critical splice donor site	probably null
R3884:Depdc5	UTSW	5	33,101,421 (GRCm39)	missense	probably damaging	1.00
R3967:Depdc5	UTSW	5	33,101,459 (GRCm39)	nonsense	probably null
R4118:Depdc5	UTSW	5	33,121,979 (GRCm39)	missense	probably damaging	1.00
R4197:Depdc5	UTSW	5	33,148,547 (GRCm39)	missense	possibly damaging	0.93
R4407:Depdc5	UTSW	5	33,061,878 (GRCm39)	critical splice donor site	probably null
R4534:Depdc5	UTSW	5	33,067,751 (GRCm39)	critical splice acceptor site	probably benign
R4535:Depdc5	UTSW	5	33,067,751 (GRCm39)	critical splice acceptor site	probably benign
R4538:Depdc5	UTSW	5	33,141,290 (GRCm39)	missense	probably damaging	1.00
R4613:Depdc5	UTSW	5	33,132,790 (GRCm39)	missense	probably damaging	1.00
R4736:Depdc5	UTSW	5	33,132,666 (GRCm39)	missense	probably benign
R4738:Depdc5	UTSW	5	33,132,666 (GRCm39)	missense	probably benign
R4765:Depdc5	UTSW	5	33,094,979 (GRCm39)	missense	probably damaging	1.00
R5021:Depdc5	UTSW	5	33,136,758 (GRCm39)	missense	probably damaging	1.00
R5261:Depdc5	UTSW	5	33,095,635 (GRCm39)	missense	probably damaging	1.00
R5541:Depdc5	UTSW	5	33,021,973 (GRCm39)	utr 5 prime	probably benign
R5594:Depdc5	UTSW	5	33,058,834 (GRCm39)	missense	possibly damaging	0.46
R5929:Depdc5	UTSW	5	33,132,850 (GRCm39)	nonsense	probably null
R6132:Depdc5	UTSW	5	33,067,811 (GRCm39)	missense	probably damaging	0.99
R6146:Depdc5	UTSW	5	33,126,075 (GRCm39)	missense	probably benign	0.01
R6336:Depdc5	UTSW	5	33,121,851 (GRCm39)	splice site	probably null
R6468:Depdc5	UTSW	5	33,069,575 (GRCm39)	missense	probably benign	0.02
R6911:Depdc5	UTSW	5	33,081,536 (GRCm39)	missense	probably damaging	1.00
R6969:Depdc5	UTSW	5	33,141,204 (GRCm39)	missense	probably damaging	1.00
R7002:Depdc5	UTSW	5	33,034,502 (GRCm39)	splice site	probably null
R7066:Depdc5	UTSW	5	33,059,192 (GRCm39)	missense	probably benign	0.08
R7231:Depdc5	UTSW	5	33,059,209 (GRCm39)	missense	possibly damaging	0.92
R7264:Depdc5	UTSW	5	33,125,089 (GRCm39)	missense	probably benign
R7302:Depdc5	UTSW	5	33,136,852 (GRCm39)	missense	probably damaging	1.00
R7386:Depdc5	UTSW	5	33,085,280 (GRCm39)	missense	probably benign
R7564:Depdc5	UTSW	5	33,058,854 (GRCm39)	missense	probably damaging	1.00
R7636:Depdc5	UTSW	5	33,075,327 (GRCm39)	missense	probably benign
R7795:Depdc5	UTSW	5	33,101,447 (GRCm39)	missense	probably damaging	1.00
R7845:Depdc5	UTSW	5	33,061,259 (GRCm39)	splice site	probably null
R8013:Depdc5	UTSW	5	33,131,186 (GRCm39)	missense	probably benign	0.01
R8037:Depdc5	UTSW	5	33,116,692 (GRCm39)	critical splice donor site	probably null
R8038:Depdc5	UTSW	5	33,116,692 (GRCm39)	critical splice donor site	probably null
R8065:Depdc5	UTSW	5	33,053,252 (GRCm39)	missense	possibly damaging	0.89
R8067:Depdc5	UTSW	5	33,053,252 (GRCm39)	missense	possibly damaging	0.89
R8108:Depdc5	UTSW	5	33,102,393 (GRCm39)	missense	probably benign	0.01
R8112:Depdc5	UTSW	5	33,126,050 (GRCm39)	missense	possibly damaging	0.67
R8213:Depdc5	UTSW	5	33,094,981 (GRCm39)	missense	probably damaging	1.00
R8382:Depdc5	UTSW	5	33,085,242 (GRCm39)	missense	probably benign	0.00
R8680:Depdc5	UTSW	5	33,101,382 (GRCm39)	missense	possibly damaging	0.48
R8743:Depdc5	UTSW	5	33,081,587 (GRCm39)	missense	probably benign	0.10
R8754:Depdc5	UTSW	5	33,136,881 (GRCm39)	missense	probably benign	0.00
R9157:Depdc5	UTSW	5	33,102,452 (GRCm39)	missense	probably damaging	0.98
R9364:Depdc5	UTSW	5	33,122,076 (GRCm39)	missense	probably benign
R9441:Depdc5	UTSW	5	33,095,042 (GRCm39)	missense	probably benign	0.03
R9450:Depdc5	UTSW	5	33,091,354 (GRCm39)	missense	probably benign
R9459:Depdc5	UTSW	5	33,148,117 (GRCm39)	missense	probably damaging	0.99
R9554:Depdc5	UTSW	5	33,122,076 (GRCm39)	missense	probably benign
R9569:Depdc5	UTSW	5	33,025,321 (GRCm39)	missense	probably damaging	0.98
R9647:Depdc5	UTSW	5	33,081,567 (GRCm39)	missense	possibly damaging	0.94
R9688:Depdc5	UTSW	5	33,055,276 (GRCm39)	nonsense	probably null
X0027:Depdc5	UTSW	5	33,061,636 (GRCm39)	missense	probably damaging	1.00
Z1176:Depdc5	UTSW	5	33,100,626 (GRCm39)	missense	possibly damaging	0.87

Predicted Primers

PCR Primer
(F):5'- TGCTCACACACTCGCTCATT -3'
(R):5'- GGGCCACCAAACCTAACTGAAAT -3'

Sequencing Primer
(F):5'- CGCTCATTTCTTTTCCAGGAGGG -3'
(R):5'- GCAAATGTCTCCATGAGATCTGGC -3'

Posted On

2016-07-06