Mutagenetix > Incidental Mutation

Incidental Mutation 'R1657:Als2'

186433

Institutional Source

Beutler Lab

Gene Symbol

Als2

Ensembl Gene

ENSMUSG00000026024

Gene Name

alsin Rho guanine nucleotide exchange factor

Synonyms

3222402C23Rik, Als2cr6, 9430073A21Rik, Alsin

MMRRC Submission

039693-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.776) question?

Stock #

R1657 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

59162926-59237231 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 59180601 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1185 (V1185A)

Ref Sequence

ENSEMBL: ENSMUSP00000125753 (fasta)

Gene Model

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

AlphaFold

Q920R0

Predicted Effect

probably damaging
Transcript: ENSMUST00000027178
AA Change: V1185A

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

SMART Domains

Protein: ENSMUSP00000027178
Gene: ENSMUSG00000026024
AA Change: V1185A

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

probably damaging
Transcript: ENSMUST00000163058
AA Change: V1185A

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

SMART Domains

Protein: ENSMUSP00000125753
Gene: ENSMUSG00000026024
AA Change: V1185A

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

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.5%
20x: 93.2%

Validation Efficiency

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: 55 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610009B22Rik	T	C	11: 51,685,678	Q131R	probably benign	Het
3632451O06Rik	G	C	14: 49,773,560	T230S	probably damaging	Het
Acaca	T	G	11: 84,264,084	D988E	probably benign	Het
Amdhd2	A	G	17: 24,156,055	V391A	probably damaging	Het
Caprin1	A	T	2: 103,769,506	V608E	probably damaging	Het
Celsr3	T	A	9: 108,842,952	C2512*	probably null	Het
Cfl1	A	T	19: 5,493,555	R187W	probably damaging	Het
Cgnl1	C	T	9: 71,725,944	V42I	probably damaging	Het
Chd2	A	G	7: 73,480,430	Y826H	probably damaging	Het
Col9a2	C	A	4: 121,040,974	P28T	unknown	Het
Cyp3a44	G	A	5: 145,779,743	P346S	probably damaging	Het
Dact2	A	G	17: 14,197,990	V151A	probably benign	Het
Dhx29	T	C	13: 112,952,843	I716T	probably damaging	Het
Esam	T	C	9: 37,537,621	S342P	probably damaging	Het
Fam189a2	C	A	19: 23,975,635	C437F	probably damaging	Het
Fer1l4	A	G	2: 156,035,598	V1053A	possibly damaging	Het
Grk3	A	G	5: 112,966,982	F124S	probably damaging	Het
H2-DMa	G	A	17: 34,137,399		probably null	Het
Hsd3b5	T	A	3: 98,619,720	I137F	possibly damaging	Het
Itgav	A	T	2: 83,801,779	I902F	probably benign	Het
Itsn1	G	T	16: 91,909,223	C179F	probably damaging	Het
Kcnh8	G	A	17: 52,839,125	R347H	probably damaging	Het
Kif9	T	C	9: 110,489,966	M166T	possibly damaging	Het
Kmt5c	C	T	7: 4,746,454	Q324*	probably null	Het
Lcn9	G	A	2: 25,824,710	E154K	probably benign	Het
Mfge8	A	T	7: 79,141,773	L227Q	probably benign	Het
Mroh2b	A	T	15: 4,931,043	R753*	probably null	Het
Mtif2	G	A	11: 29,540,721	R475Q	probably benign	Het
Nln	C	T	13: 104,036,947	V584I	possibly damaging	Het
Nr2e3	T	C	9: 59,948,767	E129G	probably benign	Het
Ocstamp	T	C	2: 165,397,516	D250G	probably damaging	Het
Olfr1065	A	C	2: 86,445,218	L255V	probably damaging	Het
Olfr403	A	T	11: 74,195,896	H131L	probably damaging	Het
Olfr503	T	C	7: 108,545,377	I284T	possibly damaging	Het
Pld1	A	T	3: 28,071,187	I417L	probably benign	Het
Polr1a	A	T	6: 71,941,535	K692N	probably damaging	Het
Qsox2	A	T	2: 26,220,747	Y152*	probably null	Het
Rpap1	T	C	2: 119,783,778	D46G	possibly damaging	Het
Rpe65	A	G	3: 159,614,448	T246A	probably damaging	Het
Scn5a	T	C	9: 119,562,380	D82G	probably damaging	Het
Sema3d	A	G	5: 12,584,974	E669G	possibly damaging	Het
Serpinb6c	T	C	13: 33,880,226	N282S	probably benign	Het
Snap47	A	T	11: 59,428,770	S181T	probably benign	Het
Snx9	A	C	17: 5,918,436	T336P	possibly damaging	Het
Sphkap	G	A	1: 83,277,515	R838*	probably null	Het
Terb1	A	T	8: 104,488,491	D284E	possibly damaging	Het
Tmem266	C	T	9: 55,418,008	A153V	probably damaging	Het
Ttn	T	C	2: 76,742,804	E25915G	possibly damaging	Het
Tubal3	A	G	13: 3,933,011	T264A	possibly damaging	Het
Vldlr	G	A	19: 27,245,670	R747Q	probably benign	Het
Zc3h8	G	T	2: 128,929,957		probably benign	Het
Zfp184	C	T	13: 21,959,273	T383M	probably damaging	Het
Zfp455	T	C	13: 67,198,639	F38S	possibly damaging	Het
Zfp746	A	G	6: 48,082,174	V167A	possibly damaging	Het
Zfp985	T	A	4: 147,584,110	N478K	probably benign	Het

Other mutations in Als2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00772:Als2	APN	1	59,169,896 (GRCm38)	nonsense	probably null
IGL00924:Als2	APN	1	59,215,862 (GRCm38)	missense	probably benign	0.03
IGL00949:Als2	APN	1	59,215,572 (GRCm38)	missense	probably damaging	1.00
IGL00950:Als2	APN	1	59,215,382 (GRCm38)	missense	probably benign	0.01
IGL01090:Als2	APN	1	59,215,616 (GRCm38)	missense	possibly damaging	0.81
IGL01116:Als2	APN	1	59,186,004 (GRCm38)	splice site	probably benign
IGL02001:Als2	APN	1	59,180,188 (GRCm38)	splice site	probably benign
IGL02075:Als2	APN	1	59,207,786 (GRCm38)	missense	probably damaging	1.00
IGL02441:Als2	APN	1	59,215,472 (GRCm38)	missense	probably damaging	0.98
IGL02728:Als2	APN	1	59,196,347 (GRCm38)	missense	probably benign	0.00
IGL02740:Als2	APN	1	59,169,919 (GRCm38)	missense	probably benign	0.01
IGL02885:Als2	APN	1	59,167,491 (GRCm38)	missense	probably benign	0.30
IGL02896:Als2	APN	1	59,183,787 (GRCm38)	missense	probably benign	0.17
IGL02978:Als2	APN	1	59,215,165 (GRCm38)	missense	probably benign	0.32
IGL03032:Als2	APN	1	59,216,030 (GRCm38)	splice site	probably benign
IGL03065:Als2	APN	1	59,215,872 (GRCm38)	missense	probably benign
IGL03212:Als2	APN	1	59,202,926 (GRCm38)	missense	probably benign	0.00
IGL03226:Als2	APN	1	59,186,520 (GRCm38)	missense	probably benign	0.43
R0014:Als2	UTSW	1	59,211,388 (GRCm38)	missense	possibly damaging	0.53
R0243:Als2	UTSW	1	59,215,387 (GRCm38)	missense	probably benign
R0326:Als2	UTSW	1	59,180,583 (GRCm38)	missense	probably damaging	1.00
R0376:Als2	UTSW	1	59,215,565 (GRCm38)	missense	probably benign	0.00
R0605:Als2	UTSW	1	59,168,414 (GRCm38)	missense	probably benign	0.02
R1607:Als2	UTSW	1	59,180,147 (GRCm38)	missense	probably damaging	1.00
R1631:Als2	UTSW	1	59,218,067 (GRCm38)	missense	probably benign	0.00
R1763:Als2	UTSW	1	59,174,991 (GRCm38)	missense	probably benign
R1950:Als2	UTSW	1	59,185,601 (GRCm38)	critical splice acceptor site	probably null
R1970:Als2	UTSW	1	59,215,169 (GRCm38)	missense	probably benign	0.34
R2151:Als2	UTSW	1	59,207,789 (GRCm38)	missense	probably damaging	1.00
R2292:Als2	UTSW	1	59,187,385 (GRCm38)	missense	probably damaging	1.00
R2513:Als2	UTSW	1	59,215,117 (GRCm38)	missense	probably benign	0.00
R2849:Als2	UTSW	1	59,206,538 (GRCm38)	missense	probably damaging	0.97
R2869:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R2869:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R2870:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R2870:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R2872:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R2872:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R2873:Als2	UTSW	1	59,211,137 (GRCm38)	missense	probably damaging	1.00
R3054:Als2	UTSW	1	59,215,494 (GRCm38)	missense	probably damaging	1.00
R3081:Als2	UTSW	1	59,187,349 (GRCm38)	missense	probably damaging	1.00
R3176:Als2	UTSW	1	59,170,008 (GRCm38)	missense	possibly damaging	0.88
R3276:Als2	UTSW	1	59,170,008 (GRCm38)	missense	possibly damaging	0.88
R3801:Als2	UTSW	1	59,167,199 (GRCm38)	missense	probably damaging	1.00
R3803:Als2	UTSW	1	59,167,199 (GRCm38)	missense	probably damaging	1.00
R3808:Als2	UTSW	1	59,170,450 (GRCm38)	missense	probably benign	0.08
R3884:Als2	UTSW	1	59,185,568 (GRCm38)	missense	probably damaging	0.99
R4012:Als2	UTSW	1	59,187,416 (GRCm38)	missense	probably benign	0.09
R4033:Als2	UTSW	1	59,196,241 (GRCm38)	missense	probably benign
R4201:Als2	UTSW	1	59,180,154 (GRCm38)	missense	possibly damaging	0.77
R4321:Als2	UTSW	1	59,167,454 (GRCm38)	splice site	probably benign
R4707:Als2	UTSW	1	59,215,313 (GRCm38)	missense	probably benign
R4784:Als2	UTSW	1	59,215,313 (GRCm38)	missense	probably benign
R4785:Als2	UTSW	1	59,215,313 (GRCm38)	missense	probably benign
R4991:Als2	UTSW	1	59,207,768 (GRCm38)	missense	probably benign	0.10
R5068:Als2	UTSW	1	59,211,274 (GRCm38)	missense	probably benign	0.13
R5110:Als2	UTSW	1	59,185,441 (GRCm38)	missense	probably damaging	0.98
R5141:Als2	UTSW	1	59,170,452 (GRCm38)	missense	possibly damaging	0.80
R5394:Als2	UTSW	1	59,174,946 (GRCm38)	missense	probably benign	0.06
R5621:Als2	UTSW	1	59,191,890 (GRCm38)	missense	probably benign	0.33
R5685:Als2	UTSW	1	59,179,091 (GRCm38)	missense	possibly damaging	0.73
R5987:Als2	UTSW	1	59,206,587 (GRCm38)	missense	probably damaging	1.00
R6012:Als2	UTSW	1	59,185,215 (GRCm38)	missense	probably damaging	1.00
R6118:Als2	UTSW	1	59,203,069 (GRCm38)	missense	possibly damaging	0.62
R6222:Als2	UTSW	1	59,180,125 (GRCm38)	missense	probably benign	0.04
R6367:Als2	UTSW	1	59,199,140 (GRCm38)	missense	probably benign	0.04
R6394:Als2	UTSW	1	59,167,197 (GRCm38)	missense	probably damaging	0.99
R6866:Als2	UTSW	1	59,211,133 (GRCm38)	missense	probably damaging	1.00
R6965:Als2	UTSW	1	59,170,557 (GRCm38)	missense	possibly damaging	0.70
R7038:Als2	UTSW	1	59,167,514 (GRCm38)	missense	possibly damaging	0.94
R7178:Als2	UTSW	1	59,207,812 (GRCm38)	missense	probably damaging	0.96
R7494:Als2	UTSW	1	59,183,166 (GRCm38)	splice site	probably null
R7541:Als2	UTSW	1	59,167,616 (GRCm38)	splice site	probably null
R7601:Als2	UTSW	1	59,170,002 (GRCm38)	missense	probably benign	0.17
R8380:Als2	UTSW	1	59,211,308 (GRCm38)	missense	probably benign
R8478:Als2	UTSW	1	59,186,016 (GRCm38)	missense	probably damaging	0.96
R8492:Als2	UTSW	1	59,211,344 (GRCm38)	missense	probably damaging	0.98
R9048:Als2	UTSW	1	59,186,511 (GRCm38)	missense	possibly damaging	0.81
R9090:Als2	UTSW	1	59,203,030 (GRCm38)	missense	probably benign	0.01
R9128:Als2	UTSW	1	59,180,550 (GRCm38)	missense	probably benign	0.00
R9206:Als2	UTSW	1	59,185,247 (GRCm38)	missense	probably damaging	1.00
R9271:Als2	UTSW	1	59,203,030 (GRCm38)	missense	probably benign	0.01
R9430:Als2	UTSW	1	59,192,039 (GRCm38)	missense	probably benign	0.00
R9455:Als2	UTSW	1	59,180,137 (GRCm38)	missense	probably damaging	1.00
R9482:Als2	UTSW	1	59,191,950 (GRCm38)	missense	probably damaging	1.00
R9494:Als2	UTSW	1	59,167,505 (GRCm38)	missense	probably damaging	1.00
R9544:Als2	UTSW	1	59,211,309 (GRCm38)	missense	probably benign	0.00
R9796:Als2	UTSW	1	59,170,442 (GRCm38)	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- TGTCCAGTCATCGGAAAATTCTCCTTC -3'
(R):5'- CAGTCCAGATTAGGCGTGTAATGCAG -3'

Sequencing Primer
(F):5'- caagagagaggcagaagcag -3'
(R):5'- TGTAATGCAGGTCCCTGTAAGAG -3'

Posted On

2014-05-09