Mutagenetix > Incidental Mutation

Incidental Mutation 'R6367:Als2'

512722

Institutional Source

Beutler Lab

Gene Symbol

Als2

Ensembl Gene

ENSMUSG00000026024

Gene Name

alsin Rho guanine nucleotide exchange factor

Synonyms

Als2cr6, 3222402C23Rik, Alsin, 9430073A21Rik

MMRRC Submission

044517-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.767) question?

Stock #

R6367 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

59202085-59276390 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 59238299 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Leucine at position 678 (V678L)

Ref Sequence

ENSEMBL: ENSMUSP00000125753 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027178] [ENSMUST00000163058]

AlphaFold

Q920R0

Predicted Effect

probably benign
Transcript: ENSMUST00000027178
AA Change: V678L

PolyPhen 2 Score 0.041 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000027178
Gene: ENSMUSG00000026024
AA Change: V678L

Domain	Start	End	E-Value	Type
Pfam:RCC1_2	93	122	1.1e-9	PFAM
Pfam:RCC1	109	165	9.5e-11	PFAM
Pfam:RCC1	170	216	6.6e-11	PFAM
low complexity region	268	282	N/A	INTRINSIC
low complexity region	465	483	N/A	INTRINSIC
Pfam:RCC1	521	568	5.4e-13	PFAM
Pfam:RCC1_2	555	584	8.3e-12	PFAM
Pfam:RCC1	571	619	3.4e-11	PFAM
Pfam:RhoGEF	688	877	6.5e-10	PFAM
PH	895	1001	2.17e0	SMART
MORN	1041	1062	1.34e-5	SMART
MORN	1064	1085	1.95e-1	SMART
MORN	1092	1113	6.68e-6	SMART
MORN	1115	1136	9.39e0	SMART
MORN	1143	1164	1.49e1	SMART
MORN	1167	1188	1.13e1	SMART
MORN	1190	1211	2.28e0	SMART
MORN	1213	1235	5.95e1	SMART
low complexity region	1470	1483	N/A	INTRINSIC
Pfam:VPS9	1546	1650	8.6e-25	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159166

Predicted Effect

probably benign
Transcript: ENSMUST00000163058
AA Change: V678L

PolyPhen 2 Score 0.041 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000125753
Gene: ENSMUSG00000026024
AA Change: V678L

Domain	Start	End	E-Value	Type
Pfam:RCC1_2	93	122	9.9e-10	PFAM
Pfam:RCC1	109	165	9.5e-12	PFAM
Pfam:RCC1	170	216	4.9e-12	PFAM
low complexity region	268	282	N/A	INTRINSIC
low complexity region	465	483	N/A	INTRINSIC
Pfam:RCC1	521	568	4.6e-14	PFAM
Pfam:RCC1_2	555	584	1.2e-11	PFAM
Pfam:RCC1	571	619	8.6e-11	PFAM
Pfam:RhoGEF	688	877	2.6e-10	PFAM
PH	895	1001	2.17e0	SMART
MORN	1041	1062	1.34e-5	SMART
MORN	1064	1085	1.95e-1	SMART
MORN	1092	1113	6.68e-6	SMART
MORN	1115	1136	9.39e0	SMART
MORN	1143	1164	1.49e1	SMART
MORN	1167	1188	1.13e1	SMART
MORN	1190	1211	2.28e0	SMART
MORN	1213	1235	5.95e1	SMART
low complexity region	1470	1483	N/A	INTRINSIC
Pfam:VPS9	1546	1650	1e-24	PFAM

Meta Mutation Damage Score

0.0651

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 97.9%
20x: 93.7%

Validation Efficiency

98% (44/45)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
PHENOTYPE: Homozygous null mutations in this gene may result in increased body weight, altered endosome trafficking, modest motor behavioral abnormalities, altered anxiety responses, impaired axonal transport, and mild neurolopathogical deficits including axonal degeneration in the corticospinal tract. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 45 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca13	A	G	11: 9,166,248 (GRCm39)	N54D	possibly damaging	Het
Abca4	A	C	3: 121,897,229 (GRCm39)	Q636P	probably damaging	Het
Agk	T	C	6: 40,363,875 (GRCm39)	F285S	probably benign	Het
Arhgap17	T	C	7: 122,907,586 (GRCm39)	*231W	probably null	Het
Atp11b	A	G	3: 35,838,686 (GRCm39)	T89A	probably damaging	Het
Axl	A	T	7: 25,486,858 (GRCm39)	C50S	probably damaging	Het
Cachd1	A	G	4: 100,860,167 (GRCm39)	D1246G	probably damaging	Het
Dip2b	A	T	15: 100,013,795 (GRCm39)	Q57L	possibly damaging	Het
Dnah14	A	G	1: 181,582,951 (GRCm39)		probably null	Het
Enpep	G	T	3: 129,125,730 (GRCm39)	T134N	possibly damaging	Het
Ets1	C	T	9: 32,645,256 (GRCm39)	Q168*	probably null	Het
Fanci	T	C	7: 79,075,943 (GRCm39)	C529R	probably damaging	Het
Fbxw28	A	G	9: 109,168,599 (GRCm39)		probably null	Het
Gucy2c	C	T	6: 136,686,776 (GRCm39)	E796K	probably damaging	Het
Igsf9b	G	A	9: 27,220,821 (GRCm39)	W62*	probably null	Het
Kcng1	C	A	2: 168,104,572 (GRCm39)	V425L	probably damaging	Het
Kndc1	T	C	7: 139,493,422 (GRCm39)	S463P	probably damaging	Het
Lrba	G	C	3: 86,275,869 (GRCm39)	A1746P	probably benign	Het
Mgat4c	G	T	10: 102,221,015 (GRCm39)		probably null	Het
Nckap1l	G	A	15: 103,384,149 (GRCm39)	M582I	probably benign	Het
Oacyl	G	T	18: 65,858,515 (GRCm39)	R207L	probably damaging	Het
Or12e13	T	C	2: 87,663,937 (GRCm39)	C185R	probably damaging	Het
Or2m12	C	T	16: 19,104,822 (GRCm39)	V224M	probably damaging	Het
Or4c52	A	G	2: 89,845,360 (GRCm39)	I29V	probably benign	Het
Or51f5	C	A	7: 102,424,036 (GRCm39)	Q102K	possibly damaging	Het
Pacsin2	C	T	15: 83,266,033 (GRCm39)	A55T	probably benign	Het
Plekhm2	T	C	4: 141,367,016 (GRCm39)	D208G	probably damaging	Het
Ptpru	T	C	4: 131,501,663 (GRCm39)	D1181G	probably benign	Het
Safb	A	G	17: 56,900,845 (GRCm39)		probably benign	Het
Scp2	T	A	4: 107,969,447 (GRCm39)	Y35F	probably damaging	Het
Secisbp2	A	G	13: 51,836,177 (GRCm39)	Y757C	probably damaging	Het
Sp110	C	T	1: 85,522,013 (GRCm39)	V97M	probably benign	Het
Ssx2ip	A	G	3: 146,124,921 (GRCm39)	Y82C	probably benign	Het
Svopl	A	T	6: 37,996,614 (GRCm39)	W288R	possibly damaging	Het
Tdg	T	C	10: 82,483,822 (GRCm39)	Y345H	possibly damaging	Het
Tmem109	A	G	19: 10,851,727 (GRCm39)	F53S	possibly damaging	Het
Tpsab1	G	T	17: 25,562,448 (GRCm39)	T293N	probably damaging	Het
Trpm8	A	G	1: 88,287,405 (GRCm39)	D796G	probably damaging	Het
Tuba1c	T	C	15: 98,935,334 (GRCm39)	I265T	probably damaging	Het
Unc80	T	C	1: 66,711,925 (GRCm39)	V2749A	probably benign	Het
Utrn	A	G	10: 12,623,719 (GRCm39)	L173P	probably damaging	Het
Vmn2r111	T	C	17: 22,778,032 (GRCm39)	N549S	possibly damaging	Het
Wbp2	G	T	11: 115,974,741 (GRCm39)	T31N	probably benign	Het
Wdr1	G	T	5: 38,703,189 (GRCm39)	A129D	possibly damaging	Het
Yod1	G	A	1: 130,645,275 (GRCm39)	G19S	probably damaging	Het

Other mutations in Als2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00772:Als2	APN	1	59,209,055 (GRCm39)	nonsense	probably null
IGL00924:Als2	APN	1	59,255,021 (GRCm39)	missense	probably benign	0.03
IGL00949:Als2	APN	1	59,254,731 (GRCm39)	missense	probably damaging	1.00
IGL00950:Als2	APN	1	59,254,541 (GRCm39)	missense	probably benign	0.01
IGL01090:Als2	APN	1	59,254,775 (GRCm39)	missense	possibly damaging	0.81
IGL01116:Als2	APN	1	59,225,163 (GRCm39)	splice site	probably benign
IGL02001:Als2	APN	1	59,219,347 (GRCm39)	splice site	probably benign
IGL02075:Als2	APN	1	59,246,945 (GRCm39)	missense	probably damaging	1.00
IGL02441:Als2	APN	1	59,254,631 (GRCm39)	missense	probably damaging	0.98
IGL02728:Als2	APN	1	59,235,506 (GRCm39)	missense	probably benign	0.00
IGL02740:Als2	APN	1	59,209,078 (GRCm39)	missense	probably benign	0.01
IGL02885:Als2	APN	1	59,206,650 (GRCm39)	missense	probably benign	0.30
IGL02896:Als2	APN	1	59,222,946 (GRCm39)	missense	probably benign	0.17
IGL02978:Als2	APN	1	59,254,324 (GRCm39)	missense	probably benign	0.32
IGL03032:Als2	APN	1	59,255,189 (GRCm39)	splice site	probably benign
IGL03065:Als2	APN	1	59,255,031 (GRCm39)	missense	probably benign
IGL03212:Als2	APN	1	59,242,085 (GRCm39)	missense	probably benign	0.00
IGL03226:Als2	APN	1	59,225,679 (GRCm39)	missense	probably benign	0.43
R0014:Als2	UTSW	1	59,250,547 (GRCm39)	missense	possibly damaging	0.53
R0243:Als2	UTSW	1	59,254,546 (GRCm39)	missense	probably benign
R0326:Als2	UTSW	1	59,219,742 (GRCm39)	missense	probably damaging	1.00
R0376:Als2	UTSW	1	59,254,724 (GRCm39)	missense	probably benign	0.00
R0605:Als2	UTSW	1	59,207,573 (GRCm39)	missense	probably benign	0.02
R1607:Als2	UTSW	1	59,219,306 (GRCm39)	missense	probably damaging	1.00
R1631:Als2	UTSW	1	59,257,226 (GRCm39)	missense	probably benign	0.00
R1657:Als2	UTSW	1	59,219,760 (GRCm39)	missense	probably damaging	1.00
R1763:Als2	UTSW	1	59,214,150 (GRCm39)	missense	probably benign
R1950:Als2	UTSW	1	59,224,760 (GRCm39)	critical splice acceptor site	probably null
R1970:Als2	UTSW	1	59,254,328 (GRCm39)	missense	probably benign	0.34
R2151:Als2	UTSW	1	59,246,948 (GRCm39)	missense	probably damaging	1.00
R2292:Als2	UTSW	1	59,226,544 (GRCm39)	missense	probably damaging	1.00
R2513:Als2	UTSW	1	59,254,276 (GRCm39)	missense	probably benign	0.00
R2849:Als2	UTSW	1	59,245,697 (GRCm39)	missense	probably damaging	0.97
R2869:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R2869:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R2870:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R2870:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R2872:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R2872:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R2873:Als2	UTSW	1	59,250,296 (GRCm39)	missense	probably damaging	1.00
R3054:Als2	UTSW	1	59,254,653 (GRCm39)	missense	probably damaging	1.00
R3081:Als2	UTSW	1	59,226,508 (GRCm39)	missense	probably damaging	1.00
R3176:Als2	UTSW	1	59,209,167 (GRCm39)	missense	possibly damaging	0.88
R3276:Als2	UTSW	1	59,209,167 (GRCm39)	missense	possibly damaging	0.88
R3801:Als2	UTSW	1	59,206,358 (GRCm39)	missense	probably damaging	1.00
R3803:Als2	UTSW	1	59,206,358 (GRCm39)	missense	probably damaging	1.00
R3808:Als2	UTSW	1	59,209,609 (GRCm39)	missense	probably benign	0.08
R3884:Als2	UTSW	1	59,224,727 (GRCm39)	missense	probably damaging	0.99
R4012:Als2	UTSW	1	59,226,575 (GRCm39)	missense	probably benign	0.09
R4033:Als2	UTSW	1	59,235,400 (GRCm39)	missense	probably benign
R4201:Als2	UTSW	1	59,219,313 (GRCm39)	missense	possibly damaging	0.77
R4321:Als2	UTSW	1	59,206,613 (GRCm39)	splice site	probably benign
R4707:Als2	UTSW	1	59,254,472 (GRCm39)	missense	probably benign
R4784:Als2	UTSW	1	59,254,472 (GRCm39)	missense	probably benign
R4785:Als2	UTSW	1	59,254,472 (GRCm39)	missense	probably benign
R4991:Als2	UTSW	1	59,246,927 (GRCm39)	missense	probably benign	0.10
R5068:Als2	UTSW	1	59,250,433 (GRCm39)	missense	probably benign	0.13
R5110:Als2	UTSW	1	59,224,600 (GRCm39)	missense	probably damaging	0.98
R5141:Als2	UTSW	1	59,209,611 (GRCm39)	missense	possibly damaging	0.80
R5394:Als2	UTSW	1	59,214,105 (GRCm39)	missense	probably benign	0.06
R5621:Als2	UTSW	1	59,231,049 (GRCm39)	missense	probably benign	0.33
R5685:Als2	UTSW	1	59,218,250 (GRCm39)	missense	possibly damaging	0.73
R5987:Als2	UTSW	1	59,245,746 (GRCm39)	missense	probably damaging	1.00
R6012:Als2	UTSW	1	59,224,374 (GRCm39)	missense	probably damaging	1.00
R6118:Als2	UTSW	1	59,242,228 (GRCm39)	missense	possibly damaging	0.62
R6222:Als2	UTSW	1	59,219,284 (GRCm39)	missense	probably benign	0.04
R6394:Als2	UTSW	1	59,206,356 (GRCm39)	missense	probably damaging	0.99
R6866:Als2	UTSW	1	59,250,292 (GRCm39)	missense	probably damaging	1.00
R6965:Als2	UTSW	1	59,209,716 (GRCm39)	missense	possibly damaging	0.70
R7038:Als2	UTSW	1	59,206,673 (GRCm39)	missense	possibly damaging	0.94
R7178:Als2	UTSW	1	59,246,971 (GRCm39)	missense	probably damaging	0.96
R7494:Als2	UTSW	1	59,222,325 (GRCm39)	splice site	probably null
R7541:Als2	UTSW	1	59,206,775 (GRCm39)	splice site	probably null
R7601:Als2	UTSW	1	59,209,161 (GRCm39)	missense	probably benign	0.17
R8380:Als2	UTSW	1	59,250,467 (GRCm39)	missense	probably benign
R8478:Als2	UTSW	1	59,225,175 (GRCm39)	missense	probably damaging	0.96
R8492:Als2	UTSW	1	59,250,503 (GRCm39)	missense	probably damaging	0.98
R9048:Als2	UTSW	1	59,225,670 (GRCm39)	missense	possibly damaging	0.81
R9090:Als2	UTSW	1	59,242,189 (GRCm39)	missense	probably benign	0.01
R9128:Als2	UTSW	1	59,219,709 (GRCm39)	missense	probably benign	0.00
R9206:Als2	UTSW	1	59,224,406 (GRCm39)	missense	probably damaging	1.00
R9271:Als2	UTSW	1	59,242,189 (GRCm39)	missense	probably benign	0.01
R9430:Als2	UTSW	1	59,231,198 (GRCm39)	missense	probably benign	0.00
R9455:Als2	UTSW	1	59,219,296 (GRCm39)	missense	probably damaging	1.00
R9482:Als2	UTSW	1	59,231,109 (GRCm39)	missense	probably damaging	1.00
R9494:Als2	UTSW	1	59,206,664 (GRCm39)	missense	probably damaging	1.00
R9544:Als2	UTSW	1	59,250,468 (GRCm39)	missense	probably benign	0.00
R9796:Als2	UTSW	1	59,209,601 (GRCm39)	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- AAACAAGAGCCCGGATGATC -3'
(R):5'- GAGCTCTGATATGCACTGTTTG -3'

Sequencing Primer
(F):5'- ATCTGGGGGTGCAGGCAG -3'
(R):5'- CAGTTTAATGACTGCTTACCAGC -3'

Posted On

2018-04-27