Mutagenetix > Incidental Mutation

Incidental Mutation 'R2292:Als2'

245015

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

040291-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.767) question?

Stock #

R2292 (G1)

Quality Score

203

Status

Validated

Chromosome

Chromosomal Location

59202085-59276390 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 59226544 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 920 (Q920R)

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: Q920R

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

SMART Domains

Protein: ENSMUSP00000027178
Gene: ENSMUSG00000026024
AA Change: Q920R

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 damaging
Transcript: ENSMUST00000163058
AA Change: Q920R

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

SMART Domains

Protein: ENSMUSP00000125753
Gene: ENSMUSG00000026024
AA Change: Q920R

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

0.1592

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 94.8%

Validation Efficiency

100% (44/44)

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
4932414N04Rik	T	C	2: 68,562,483 (GRCm39)	I370T	probably benign	Het
A2m	A	G	6: 121,650,518 (GRCm39)	T1209A	possibly damaging	Het
Arhgap20	T	A	9: 51,760,743 (GRCm39)	Y829N	possibly damaging	Het
Arhgap35	A	T	7: 16,297,476 (GRCm39)	F530I	probably damaging	Het
Arid4a	G	T	12: 71,108,315 (GRCm39)	G40V	probably damaging	Het
Ascc2	T	C	11: 4,629,352 (GRCm39)		probably benign	Het
Cacna1b	C	T	2: 24,496,632 (GRCm39)	V2312I	probably benign	Het
Dctn6	T	C	8: 34,559,679 (GRCm39)	T159A	probably benign	Het
Ddx55	G	T	5: 124,706,140 (GRCm39)	A522S	probably benign	Het
Dnah6	G	A	6: 72,998,092 (GRCm39)	T4110I	probably damaging	Het
Dvl1	G	A	4: 155,932,273 (GRCm39)	V28I	possibly damaging	Het
Dym	A	G	18: 75,332,283 (GRCm39)	T504A	possibly damaging	Het
E130308A19Rik	T	C	4: 59,690,579 (GRCm39)	Y138H	probably damaging	Het
Fgd4	A	T	16: 16,253,864 (GRCm39)	C568S	possibly damaging	Het
Fkbp4	A	C	6: 128,413,625 (GRCm39)	V6G	probably damaging	Het
Flg2	A	T	3: 93,127,984 (GRCm39)	S2299C	unknown	Het
Gdf2	A	T	14: 33,667,145 (GRCm39)	N289I	possibly damaging	Het
Gpr182	A	G	10: 127,586,051 (GRCm39)	I300T	possibly damaging	Het
Iqcg	A	G	16: 32,870,253 (GRCm39)	V80A	probably benign	Het
Letm1	A	AG	5: 33,926,859 (GRCm39)		probably null	Het
Lyst	T	G	13: 13,915,080 (GRCm39)	F3258C	probably damaging	Het
Map3k12	T	C	15: 102,408,574 (GRCm39)	E870G	probably damaging	Het
Mphosph10	G	A	7: 64,035,519 (GRCm39)	P384L	probably damaging	Het
Ncoa4	T	G	14: 31,895,413 (GRCm39)	L179R	probably damaging	Het
Nlrp1c-ps	A	G	11: 71,137,188 (GRCm39)		noncoding transcript	Het
Nwd2	A	T	5: 63,962,917 (GRCm39)	M834L	probably benign	Het
Or10a49	A	T	7: 108,468,223 (GRCm39)	M46K	probably benign	Het
Or2w6	A	G	13: 21,843,001 (GRCm39)	M164T	probably damaging	Het
Pccb	T	C	9: 100,876,685 (GRCm39)	E266G	probably benign	Het
Pcdhb2	T	A	18: 37,430,297 (GRCm39)		probably null	Het
Pramel25	T	C	4: 143,520,446 (GRCm39)	I66T	probably benign	Het
Prdm13	A	C	4: 21,683,914 (GRCm39)	I119S	unknown	Het
Tchh	A	G	3: 93,349,689 (GRCm39)	Y18C	probably damaging	Het
Tmem192	T	C	8: 65,411,998 (GRCm39)	V59A	probably damaging	Het
Trak2	A	T	1: 58,974,916 (GRCm39)	F92Y	probably damaging	Het
Trappc11	C	T	8: 47,958,771 (GRCm39)	G40D	probably damaging	Het
Ttc23	A	T	7: 67,319,535 (GRCm39)	I132F	probably benign	Het
Ttc9b	A	G	7: 27,355,405 (GRCm39)	D225G	probably benign	Het
Ubr3	G	T	2: 69,727,604 (GRCm39)		probably benign	Het
Vmn2r75	A	C	7: 85,798,144 (GRCm39)	C556W	probably damaging	Het
Zbtb41	T	C	1: 139,368,097 (GRCm39)	V595A	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
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
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'- TATGAGTACACTGACATTCGTGTAG -3'
(R):5'- AGCCTTTGCCCTTAGGTTTG -3'

Sequencing Primer
(F):5'- ACACTGACATTCGTGTAGCAGTG -3'
(R):5'- GCCCTTAGGTTTGCTTGCTACTG -3'

Posted On

2014-10-30