Mutagenetix > Incidental Mutations

Incidental Mutation 'R2870:Als2'

266479

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

040458-MU

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.768) question?

Stock #

R2870 (G1)

Quality Score

157

Status

Not validated

Chromosome

Chromosomal Location

59162926-59237231 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 59211137 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 483 (S483P)

Ref Sequence

ENSEMBL: ENSMUSP00000125753 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000027178
AA Change: S483P

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

SMART Domains

Protein: ENSMUSP00000027178
Gene: ENSMUSG00000026024
AA Change: S483P

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: S483P

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

SMART Domains

Protein: ENSMUSP00000125753
Gene: ENSMUSG00000026024
AA Change: S483P

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

0.2035

Coding Region Coverage

1x: 99.1%
3x: 98.6%
10x: 97.3%
20x: 95.0%

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930444G20Rik	A	T	10: 22,067,379	I234N	probably benign	Het
Actrt3	A	G	3: 30,599,698	V51A	probably damaging	Het
Adgb	C	T	10: 10,431,281		probably null	Het
AI481877	A	C	4: 59,093,850	L226R	probably damaging	Het
Ankrd10	C	T	8: 11,615,682	R306H	probably damaging	Het
Arhgef10	T	C	8: 14,975,093		probably null	Het
Arhgef10	A	G	8: 14,975,666	I459V	probably benign	Het
Armc2	C	T	10: 41,966,700		probably null	Het
Atp12a	A	G	14: 56,386,950	R952G	possibly damaging	Het
Atp6v1g1	A	G	4: 63,550,021	Y87C	probably benign	Het
C030034I22Rik	T	A	17: 69,418,111		noncoding transcript	Het
Cacna2d1	G	A	5: 16,312,568	C404Y	probably damaging	Het
Ccdc163	T	C	4: 116,741,861		silent	Het
Ccdc59	A	T	10: 105,841,527	K9M	possibly damaging	Het
Cd6	A	G	19: 10,794,626	I307T	possibly damaging	Het
Clasrp	C	A	7: 19,585,240		probably benign	Het
Csmd2	T	C	4: 128,557,718	F113S	unknown	Het
Csmd3	C	T	15: 47,857,924	G1437D	probably damaging	Het
Cyp4a14	C	A	4: 115,487,301	G456W	probably damaging	Het
Cyp4a30b	A	G	4: 115,458,362	H260R	possibly damaging	Het
Dcp1b	C	T	6: 119,214,774	S217L	probably benign	Het
Dhx57	A	T	17: 80,251,376	D1051E	probably benign	Het
Dmp1	A	G	5: 104,212,108	S217G	probably benign	Het
Eif4enif1	C	T	11: 3,242,586	P805S	probably damaging	Het
Eral1	A	G	11: 78,076,278	I164T	possibly damaging	Het
Esr1	G	A	10: 4,997,890	R481H	probably damaging	Het
Fam19a2	A	T	10: 123,704,365	H42L	possibly damaging	Het
Fan1	A	G	7: 64,363,190	I668T	probably benign	Het
Gbp11	C	T	5: 105,331,000	D191N	probably benign	Het
Gm21759	T	A	5: 8,180,863		probably benign	Het
Gm5454	C	A	13: 103,357,523		noncoding transcript	Het
Gm9874	A	T	17: 30,485,789		probably benign	Het
Gria2	G	A	3: 80,702,492	T670I	probably damaging	Het
Gria4	T	A	9: 4,503,614	N334I	probably damaging	Het
Grm5	T	C	7: 87,602,722	V60A	possibly damaging	Het
Ift172	C	T	5: 31,257,861	V1335I	probably benign	Het
Ino80d	C	T	1: 63,061,039		probably null	Het
Kif1c	A	G	11: 70,724,081	E567G	probably damaging	Het
Krt31	T	G	11: 100,047,873	N298T	possibly damaging	Het
Mapk7	C	A	11: 61,490,212		probably benign	Het
March8	C	T	6: 116,401,145		probably benign	Het
Matr3	T	A	18: 35,572,296	S91R	probably benign	Het
Mdm1	A	G	10: 118,150,942	T267A	probably benign	Het
Mlxip	A	G	5: 123,452,667	M878V	probably benign	Het
Mtm1	T	C	X: 71,296,362		probably benign	Homo
Mtor	T	A	4: 148,540,030	M2089K	probably benign	Het
Mylk2	A	G	2: 152,919,348	K457R	probably damaging	Het
Nell1	A	T	7: 50,249,657		probably benign	Het
Nomo1	C	A	7: 46,046,937	T293N	probably damaging	Het
Odf3l2	G	A	10: 79,645,653	T14I	probably benign	Het
Olfr1080	T	C	2: 86,553,584	D180G	possibly damaging	Het
Olfr1510	T	G	14: 52,410,861	T4P	probably benign	Het
Olfr801	A	T	10: 129,669,759	C253*	probably null	Het
Ostc	T	C	3: 130,703,508	N80S	probably damaging	Het
Otud4	T	A	8: 79,661,073	N300K	possibly damaging	Het
Otx1	A	G	11: 21,998,681		probably benign	Het
Palmd	T	C	3: 116,923,751	R366G	possibly damaging	Het
Pcdhb20	A	T	18: 37,505,780	Q453L	possibly damaging	Het
Pcdhga9	T	A	18: 37,737,471	Y118N	possibly damaging	Het
Pes1	C	A	11: 3,976,834	T372K	probably benign	Het
Plcl1	A	T	1: 55,697,150	D550V	probably benign	Het
Plekhg5	T	A	4: 152,107,503	C433S	probably benign	Het
Plin2	A	G	4: 86,668,678	M1T	probably null	Het
Pold1	C	T	7: 44,543,347		silent	Het
Ppp1r7	T	A	1: 93,357,863		probably null	Het
Psmb8	T	C	17: 34,200,170	I146T	probably damaging	Het
Pzp	A	T	6: 128,485,556		probably null	Het
Rel	T	C	11: 23,761,129	I13V	probably benign	Het
Reln	C	T	5: 22,049,791	V527I	possibly damaging	Het
Retnla	A	G	16: 48,843,612	R90G	probably benign	Het
Slc39a8	T	A	3: 135,886,793		probably null	Het
Slc5a8	A	G	10: 88,904,963	I247V	probably benign	Het
Son	A	G	16: 91,664,317		probably null	Het
Spcs2	T	C	7: 99,839,761	D240G	probably damaging	Het
St5	A	T	7: 109,557,430	Y38N	probably benign	Het
Stx3	A	T	19: 11,789,574	V91D	probably damaging	Het
Taf6l	A	G	19: 8,778,628		probably benign	Het
Tbc1d8	A	G	1: 39,405,317	F187S	probably damaging	Het
Thbs1	C	G	2: 118,119,378	N611K	probably damaging	Het
Tipin	A	C	9: 64,304,327	S232R	probably benign	Het
Tmem132b	A	G	5: 125,638,268	D347G	probably benign	Het
Tmem161a	C	T	8: 70,178,915		probably benign	Het
Vmn2r68	A	C	7: 85,233,626	M306R	probably benign	Het
Vwa7	G	A	17: 35,021,242	M395I	probably damaging	Het
Ybx3	G	A	6: 131,370,413	A253V	probably damaging	Het
Zfp53	A	T	17: 21,508,078	E124D	probably benign	Het
Zzz3	T	A	3: 152,446,844		silent	Het

Other mutations in Als2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00772:Als2	APN	1	59169896	nonsense	probably null
IGL00924:Als2	APN	1	59215862	missense	probably benign	0.03
IGL00949:Als2	APN	1	59215572	missense	probably damaging	1.00
IGL00950:Als2	APN	1	59215382	missense	probably benign	0.01
IGL01090:Als2	APN	1	59215616	missense	possibly damaging	0.81
IGL01116:Als2	APN	1	59186004	splice site	probably benign
IGL02001:Als2	APN	1	59180188	splice site	probably benign
IGL02075:Als2	APN	1	59207786	missense	probably damaging	1.00
IGL02441:Als2	APN	1	59215472	missense	probably damaging	0.98
IGL02728:Als2	APN	1	59196347	missense	probably benign	0.00
IGL02740:Als2	APN	1	59169919	missense	probably benign	0.01
IGL02885:Als2	APN	1	59167491	missense	probably benign	0.30
IGL02896:Als2	APN	1	59183787	missense	probably benign	0.17
IGL02978:Als2	APN	1	59215165	missense	probably benign	0.32
IGL03032:Als2	APN	1	59216030	splice site	probably benign
IGL03065:Als2	APN	1	59215872	missense	probably benign
IGL03212:Als2	APN	1	59202926	missense	probably benign	0.00
IGL03226:Als2	APN	1	59186520	missense	probably benign	0.43
R0014:Als2	UTSW	1	59211388	missense	possibly damaging	0.53
R0243:Als2	UTSW	1	59215387	missense	probably benign
R0326:Als2	UTSW	1	59180583	missense	probably damaging	1.00
R0376:Als2	UTSW	1	59215565	missense	probably benign	0.00
R0605:Als2	UTSW	1	59168414	missense	probably benign	0.02
R1607:Als2	UTSW	1	59180147	missense	probably damaging	1.00
R1631:Als2	UTSW	1	59218067	missense	probably benign	0.00
R1657:Als2	UTSW	1	59180601	missense	probably damaging	1.00
R1763:Als2	UTSW	1	59174991	missense	probably benign
R1950:Als2	UTSW	1	59185601	critical splice acceptor site	probably null
R1970:Als2	UTSW	1	59215169	missense	probably benign	0.34
R2151:Als2	UTSW	1	59207789	missense	probably damaging	1.00
R2292:Als2	UTSW	1	59187385	missense	probably damaging	1.00
R2513:Als2	UTSW	1	59215117	missense	probably benign	0.00
R2849:Als2	UTSW	1	59206538	missense	probably damaging	0.97
R2869:Als2	UTSW	1	59211137	missense	probably damaging	1.00
R2869:Als2	UTSW	1	59211137	missense	probably damaging	1.00
R2870:Als2	UTSW	1	59211137	missense	probably damaging	1.00
R2872:Als2	UTSW	1	59211137	missense	probably damaging	1.00
R2872:Als2	UTSW	1	59211137	missense	probably damaging	1.00
R2873:Als2	UTSW	1	59211137	missense	probably damaging	1.00
R3054:Als2	UTSW	1	59215494	missense	probably damaging	1.00
R3081:Als2	UTSW	1	59187349	missense	probably damaging	1.00
R3176:Als2	UTSW	1	59170008	missense	possibly damaging	0.88
R3276:Als2	UTSW	1	59170008	missense	possibly damaging	0.88
R3801:Als2	UTSW	1	59167199	missense	probably damaging	1.00
R3803:Als2	UTSW	1	59167199	missense	probably damaging	1.00
R3808:Als2	UTSW	1	59170450	missense	probably benign	0.08
R3884:Als2	UTSW	1	59185568	missense	probably damaging	0.99
R4012:Als2	UTSW	1	59187416	missense	probably benign	0.09
R4033:Als2	UTSW	1	59196241	missense	probably benign
R4201:Als2	UTSW	1	59180154	missense	possibly damaging	0.77
R4321:Als2	UTSW	1	59167454	splice site	probably benign
R4707:Als2	UTSW	1	59215313	missense	probably benign
R4784:Als2	UTSW	1	59215313	missense	probably benign
R4785:Als2	UTSW	1	59215313	missense	probably benign
R4991:Als2	UTSW	1	59207768	missense	probably benign	0.10
R5068:Als2	UTSW	1	59211274	missense	probably benign	0.13
R5110:Als2	UTSW	1	59185441	missense	probably damaging	0.98
R5141:Als2	UTSW	1	59170452	missense	possibly damaging	0.80
R5394:Als2	UTSW	1	59174946	missense	probably benign	0.06
R5621:Als2	UTSW	1	59191890	missense	probably benign	0.33
R5685:Als2	UTSW	1	59179091	missense	possibly damaging	0.73
R5987:Als2	UTSW	1	59206587	missense	probably damaging	1.00
R6012:Als2	UTSW	1	59185215	missense	probably damaging	1.00
R6118:Als2	UTSW	1	59203069	missense	possibly damaging	0.62
R6222:Als2	UTSW	1	59180125	missense	probably benign	0.04
R6367:Als2	UTSW	1	59199140	missense	probably benign	0.04
R6394:Als2	UTSW	1	59167197	missense	probably damaging	0.99
R6866:Als2	UTSW	1	59211133	missense	probably damaging	1.00
R6965:Als2	UTSW	1	59170557	missense	possibly damaging	0.70
R7038:Als2	UTSW	1	59167514	missense	possibly damaging	0.94
R7178:Als2	UTSW	1	59207812	missense	probably damaging	0.96
R7494:Als2	UTSW	1	59183166	splice site	probably null
R7541:Als2	UTSW	1	59167616	splice site	probably null
R7601:Als2	UTSW	1	59170002	missense	probably benign	0.17
R8380:Als2	UTSW	1	59211308	missense	probably benign
R8478:Als2	UTSW	1	59186016	missense	probably damaging	0.96
R8492:Als2	UTSW	1	59211344	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- TGAAGCAGAGAAACTGATAGCTTTC -3'
(R):5'- GAGACGGCAGCTCAGTCG -3'

Sequencing Primer
(F):5'- AGTTGACTGTGAGCATCCAC -3'
(R):5'- AGCTCAGTCGGGCAGTG -3'

Posted On

2015-02-18