Incidental Mutation 'R2849:Als2'
ID 251904
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 040442-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.733) question?
Stock # R2849 (G1)
Quality Score 225
Status Not validated
Chromosome 1
Chromosomal Location 59202085-59276390 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 59245697 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Methionine at position 593 (T593M)
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: T593M

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000027178
Gene: ENSMUSG00000026024
AA Change: T593M

DomainStartEndE-ValueType
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: T593M

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000125753
Gene: ENSMUSG00000026024
AA Change: T593M

DomainStartEndE-ValueType
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: 99.2%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 94.8%
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: 61 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca17 G C 17: 24,508,481 (GRCm39) T1018R probably damaging Het
Abca8a T C 11: 109,932,931 (GRCm39) D1231G probably damaging Het
Adcy7 A G 8: 89,054,021 (GRCm39) I1017V probably benign Het
Agpat2 A G 2: 26,487,251 (GRCm39) I109T probably damaging Het
Aldh9a1 G A 1: 167,180,197 (GRCm39) R97H probably damaging Het
Ap3d1 G C 10: 80,577,742 (GRCm39) H28Q possibly damaging Het
Atxn1 A T 13: 45,720,175 (GRCm39) D573E probably damaging Het
Begain T A 12: 108,999,044 (GRCm39) M576L probably benign Het
Bod1l T C 5: 41,995,419 (GRCm39) N109S probably damaging Het
Boll A G 1: 55,385,532 (GRCm39) M131T possibly damaging Het
Celf2 T C 2: 6,608,936 (GRCm39) R282G probably damaging Het
Cers2 T C 3: 95,229,770 (GRCm39) F330L probably benign Het
Chst13 T C 6: 90,286,140 (GRCm39) D274G probably benign Het
Cimap1a A G 7: 140,429,182 (GRCm39) T156A probably benign Het
Cstdc5 T A 16: 36,187,814 (GRCm39) Q17L probably damaging Het
Dclk2 A G 3: 86,700,530 (GRCm39) V649A probably damaging Het
Deaf1 T C 7: 140,894,367 (GRCm39) *54W probably null Het
Fbf1 C T 11: 116,048,514 (GRCm39) probably null Het
Fbxo32 C T 15: 58,071,368 (GRCm39) S71N probably benign Het
Fbxo42 T A 4: 140,927,821 (GRCm39) N700K probably damaging Het
Fis1 T C 5: 136,991,971 (GRCm39) I55T possibly damaging Het
Fyco1 A T 9: 123,663,891 (GRCm39) L121* probably null Het
Gm2381 G A 7: 42,469,831 (GRCm39) P98S probably damaging Het
Grm7 G T 6: 110,623,309 (GRCm39) V161F probably damaging Het
Gtf2ird1 G A 5: 134,387,861 (GRCm39) T946I probably damaging Het
Hmcn1 G T 1: 150,439,350 (GRCm39) Y5494* probably null Het
Josd2 A G 7: 44,118,397 (GRCm39) probably null Het
Lfng T A 5: 140,597,622 (GRCm39) D149E probably damaging Het
Lrp1 C T 10: 127,378,165 (GRCm39) A4052T probably damaging Het
Lrrtm3 T C 10: 63,924,810 (GRCm39) N119S probably damaging Het
Lypd6 C T 2: 50,055,664 (GRCm39) P38L probably damaging Het
Msl3l2 T C 10: 55,991,538 (GRCm39) C88R probably benign Het
Nsd1 A G 13: 55,361,505 (GRCm39) T158A probably damaging Het
Nudt22 A T 19: 6,970,852 (GRCm39) S239R probably benign Het
Or4g7 T C 2: 111,309,699 (GRCm39) M190T probably benign Het
Or52r1c A T 7: 102,735,319 (GRCm39) D193V probably damaging Het
Osbpl8 T A 10: 111,105,297 (GRCm39) S251T probably benign Het
Otop3 T C 11: 115,235,384 (GRCm39) F339L probably damaging Het
Pcdhga10 T A 18: 37,881,253 (GRCm39) V338E possibly damaging Het
Pcnx2 A G 8: 126,487,666 (GRCm39) F1779S probably damaging Het
Plxna4 T C 6: 32,162,467 (GRCm39) K1349E probably damaging Het
Poteg A T 8: 27,971,704 (GRCm39) N406I probably benign Het
Ppp4r4 T C 12: 103,573,192 (GRCm39) V697A probably benign Het
Ptpra C A 2: 130,386,919 (GRCm39) H603Q probably benign Het
Rnf10 T C 5: 115,387,171 (GRCm39) D439G probably benign Het
Rnf43 T A 11: 87,623,093 (GRCm39) N731K probably benign Het
Slc2a4 T A 11: 69,836,997 (GRCm39) N116Y probably damaging Het
Slc6a15 C A 10: 103,240,552 (GRCm39) H392N probably benign Het
Slco6d1 C T 1: 98,394,441 (GRCm39) T375I probably benign Het
Smpd4 A G 16: 17,460,076 (GRCm39) D436G probably damaging Het
Spata22 G A 11: 73,244,571 (GRCm39) W311* probably null Het
Syt3 G A 7: 44,042,866 (GRCm39) V383I probably benign Het
Tle6 T A 10: 81,430,235 (GRCm39) I306F probably damaging Het
Tox3 G A 8: 90,975,018 (GRCm39) Q538* probably null Het
Trim24 T A 6: 37,933,388 (GRCm39) S656T probably damaging Het
Trnau1ap C A 4: 132,049,045 (GRCm39) V119F possibly damaging Het
Vmn1r181 G T 7: 23,683,943 (GRCm39) S136I possibly damaging Het
Vmn1r82 T C 7: 12,039,333 (GRCm39) V202A probably damaging Het
Zfp607b G A 7: 27,401,819 (GRCm39) V92I probably benign Het
Zfp964 G C 8: 70,116,504 (GRCm39) C368S unknown Het
Zw10 A G 9: 48,968,941 (GRCm39) probably null Het
Other mutations in Als2
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- GGAAAAGGAATGGCTTTGTGTC -3'
(R):5'- AGCAGGCCAGGTTTCATTTC -3'

Sequencing Primer
(F):5'- AGGAATGGCTTTGTGTCATAAAG -3'
(R):5'- AATCCAAGCTGCTGGTACTG -3'
Posted On 2014-12-04