Mutagenetix > Incidental Mutation

Incidental Mutation 'R3054:Als2'

265055

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

040563-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.767) question?

Stock #

R3054 (G1)

Quality Score

135

Status

Not validated

Chromosome

Chromosomal Location

59202085-59276390 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 59254653 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Arginine at position 235 (C235R)

Ref Sequence

ENSEMBL: ENSMUSP00000125753 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027178] [ENSMUST00000160945] [ENSMUST00000163058]

AlphaFold

Q920R0

Predicted Effect

probably damaging
Transcript: ENSMUST00000027178
AA Change: C235R

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000027178
Gene: ENSMUSG00000026024
AA Change: C235R

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: ENSMUST00000160945

SMART Domains

Protein: ENSMUSP00000140990
Gene: ENSMUSG00000026024

Domain	Start	End	E-Value	Type
Pfam:RCC1	1	52	3.3e-8	PFAM
Pfam:RCC1_2	39	66	4.1e-5	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000163058
AA Change: C235R

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000125753
Gene: ENSMUSG00000026024
AA Change: C235R

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000188469

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.4%
20x: 95.5%

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: 41 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5730596B20Rik	A	T	6: 52,156,108 (GRCm39)		probably benign	Het
Aldh1l2	T	C	10: 83,338,336 (GRCm39)	K528E	probably benign	Het
Armc6	C	A	8: 70,677,799 (GRCm39)	V177L	probably benign	Het
Asb7	A	T	7: 66,328,959 (GRCm39)	V27D	probably damaging	Het
Bard1	A	G	1: 71,127,390 (GRCm39)	V73A	possibly damaging	Het
Ccdc150	A	G	1: 54,328,001 (GRCm39)	N361S	possibly damaging	Het
Cntn5	A	G	9: 10,419,076 (GRCm39)	L7P	probably benign	Het
Cst3	A	G	2: 148,713,951 (GRCm39)	S118P	probably damaging	Het
Cyp2a22	T	C	7: 26,638,254 (GRCm39)	D84G	probably damaging	Het
Ddo	A	G	10: 40,507,738 (GRCm39)	N45S	probably benign	Het
Drd4	T	C	7: 140,874,392 (GRCm39)	V319A	probably damaging	Het
Fat3	C	T	9: 15,871,792 (GRCm39)	R3533H	probably benign	Het
Fras1	A	T	5: 96,912,802 (GRCm39)	I3369F	probably damaging	Het
Gm5591	T	C	7: 38,220,058 (GRCm39)	S272G	probably benign	Het
Gm8444	A	T	15: 81,727,845 (GRCm39)		probably benign	Het
Gm9776	A	G	13: 94,495,158 (GRCm39)		probably benign	Het
Kdm1b	C	T	13: 47,216,553 (GRCm39)	R308W	probably damaging	Het
Larp1b	A	T	3: 40,918,535 (GRCm39)	I59F	probably benign	Het
Ltn1	C	T	16: 87,200,961 (GRCm39)	A1092T	probably benign	Het
Map1b	A	G	13: 99,569,250 (GRCm39)	V1157A	unknown	Het
Mboat1	A	T	13: 30,379,724 (GRCm39)	M92L	probably benign	Het
Meis3	G	T	7: 15,916,378 (GRCm39)	L284F	probably damaging	Het
Muc20	T	C	16: 32,599,403 (GRCm39)	F3317L	probably benign	Het
Muc5b	G	T	7: 141,417,778 (GRCm39)	V3575F	probably damaging	Het
Polr1e	C	T	4: 45,018,724 (GRCm39)	T18I	possibly damaging	Het
Ppp4r1	G	T	17: 66,143,074 (GRCm39)	A764S	probably damaging	Het
Psg29	A	G	7: 16,942,727 (GRCm39)	T243A	probably benign	Het
Ptprn2	T	C	12: 116,685,753 (GRCm39)	Y71H	probably damaging	Het
Radx	T	A	X: 138,412,306 (GRCm39)	V439E	possibly damaging	Het
Rufy4	T	C	1: 74,186,822 (GRCm39)	C537R	probably damaging	Het
Sh3bp1	C	T	15: 78,795,622 (GRCm39)	P584S	probably benign	Het
Slc4a4	T	C	5: 89,373,807 (GRCm39)	V971A	probably damaging	Het
Stil	T	A	4: 114,862,163 (GRCm39)	H35Q	probably damaging	Het
Strn	A	T	17: 78,990,321 (GRCm39)	V65D	probably damaging	Het
Sumf1	T	C	6: 108,130,165 (GRCm39)	N185D	probably benign	Het
Timm29	T	C	9: 21,504,887 (GRCm39)	M185T	probably damaging	Het
Tjp3	T	C	10: 81,116,341 (GRCm39)	K251R	probably benign	Het
Tubgcp6	A	T	15: 89,006,806 (GRCm39)	M72K	probably damaging	Het
Utp14b	T	A	1: 78,642,442 (GRCm39)	D113E	possibly damaging	Het
Vps13b	A	G	15: 35,646,507 (GRCm39)	E1537G	probably damaging	Het
Zfr	A	G	15: 12,154,593 (GRCm39)	N592S	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
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
R6367:Als2	UTSW	1	59,238,299 (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'- CAGTTCAGCTTCTACCACCG -3'
(R):5'- CACTCAGCAGAGAGATCTGG -3'

Sequencing Primer
(F):5'- TCTACCACCGTGTTCTCAAAC -3'
(R):5'- CTCAGCAGAGAGATCTGGGCATG -3'

Posted On

2015-02-05