Phenotypic Mutation '50-cal' (pdf version)
Allele | 50-cal |
Mutation Type |
critical splice donor site
(2 bp from exon)
|
Chromosome | 13 |
Coordinate | 13,882,797 bp (GRCm39) |
Base Change | T ⇒ A (forward strand) |
Gene |
Lyst
|
Gene Name | lysosomal trafficking regulator |
Synonym(s) | D13Sfk13 |
Chromosomal Location |
13,764,982-13,953,388 bp (+) (GRCm39)
|
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Mutations in this gene are associated with Chediak-Higashi syndrome, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants, though the full-length nature of some of these variants has not been determined. [provided by RefSeq, Apr 2013] PHENOTYPE: Homozygous mice have a phenotype similar to human Chediak-Higashi syndrome patients, exhibiting lysosomal dysfunction with resultant protein storage; diluted coat color; abnormal melanogenesis; immune cell dysfunction resulting in increased susceptibility to bacterial, viral, and parasitic infections and decreased cytotoxic activity against tumor cells. [provided by MGI curators]
|
Accession Number | NCBI RefSeq: NM_010748; MGI: 107448
|
Mapped | Yes |
Amino Acid Change |
|
Institutional Source | Beutler Lab |
Gene Model |
predicted gene model for protein(s):
[ENSMUSP00000106188 †]
† probably from a misspliced transcript
|
AlphaFold |
no structure available at present |
SMART Domains |
Protein: ENSMUSP00000106188 Gene: ENSMUSG00000019726
Domain | Start | End | E-Value | Type |
low complexity region
|
26 |
36 |
N/A |
INTRINSIC |
low complexity region
|
72 |
82 |
N/A |
INTRINSIC |
low complexity region
|
399 |
412 |
N/A |
INTRINSIC |
low complexity region
|
1333 |
1344 |
N/A |
INTRINSIC |
low complexity region
|
2295 |
2307 |
N/A |
INTRINSIC |
low complexity region
|
2427 |
2445 |
N/A |
INTRINSIC |
low complexity region
|
2534 |
2546 |
N/A |
INTRINSIC |
Pfam:PH_BEACH
|
3006 |
3101 |
5.8e-25 |
PFAM |
Beach
|
3118 |
3408 |
1.25e-193 |
SMART |
Blast:Beach
|
3441 |
3478 |
9e-13 |
BLAST |
WD40
|
3539 |
3579 |
5.75e-1 |
SMART |
WD40
|
3591 |
3630 |
2.89e-5 |
SMART |
WD40
|
3633 |
3676 |
1.38e0 |
SMART |
WD40
|
3724 |
3765 |
1.27e-1 |
SMART |
|
Predicted Effect |
probably null
|
Meta Mutation Damage Score |
0.9485 |
Is this an essential gene? |
Possibly nonessential (E-score: 0.395) |
Phenotypic Category |
Autosomal Recessive |
Candidate Explorer Status |
loading ... |
Single pedigree Linkage Analysis Data
|
|
Penetrance | |
Alleles Listed at MGI | All mutations/alleles(53) : Chemically induced (ENU)(6) Gene trapped(34) Radiation induced(1) Spontaneous(8) Targeted(4)
|
Lab Alleles |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00156:Lyst
|
APN |
13 |
13823463 |
missense |
probably benign |
|
IGL00474:Lyst
|
APN |
13 |
13818121 |
missense |
possibly damaging |
0.48 |
IGL00484:Lyst
|
APN |
13 |
13884188 |
missense |
probably benign |
0.02 |
IGL00492:Lyst
|
APN |
13 |
13852760 |
missense |
possibly damaging |
0.54 |
IGL00807:Lyst
|
APN |
13 |
13825008 |
missense |
possibly damaging |
0.91 |
IGL00949:Lyst
|
APN |
13 |
13810070 |
missense |
possibly damaging |
0.87 |
IGL00952:Lyst
|
APN |
13 |
13852692 |
missense |
probably benign |
0.05 |
IGL01305:Lyst
|
APN |
13 |
13852641 |
missense |
probably benign |
0.01 |
IGL01317:Lyst
|
APN |
13 |
13845455 |
missense |
probably benign |
|
IGL01419:Lyst
|
APN |
13 |
13810423 |
missense |
probably benign |
0.00 |
IGL01445:Lyst
|
APN |
13 |
13826299 |
missense |
probably benign |
0.00 |
IGL01690:Lyst
|
APN |
13 |
13917831 |
missense |
probably damaging |
1.00 |
IGL01791:Lyst
|
APN |
13 |
13809887 |
missense |
probably damaging |
1.00 |
IGL01809:Lyst
|
APN |
13 |
13812388 |
missense |
probably damaging |
1.00 |
IGL01896:Lyst
|
APN |
13 |
13810162 |
missense |
probably benign |
0.04 |
IGL01938:Lyst
|
APN |
13 |
13812009 |
missense |
possibly damaging |
0.93 |
IGL01986:Lyst
|
APN |
13 |
13950212 |
critical splice donor site |
probably null |
|
IGL02022:Lyst
|
APN |
13 |
13838629 |
nonsense |
probably null |
|
IGL02044:Lyst
|
APN |
13 |
13887431 |
missense |
probably damaging |
1.00 |
IGL02157:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02185:Lyst
|
APN |
13 |
13835678 |
nonsense |
probably null |
|
IGL02215:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02245:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02246:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02247:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02297:Lyst
|
APN |
13 |
13812677 |
nonsense |
probably null |
|
IGL02411:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02415:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02419:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02420:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02429:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02501:Lyst
|
APN |
13 |
13886230 |
missense |
probably benign |
0.02 |
IGL02522:Lyst
|
APN |
13 |
13809290 |
missense |
possibly damaging |
0.81 |
IGL02535:Lyst
|
APN |
13 |
13824927 |
missense |
probably benign |
0.00 |
IGL02596:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02601:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02603:Lyst
|
APN |
13 |
13835541 |
missense |
probably benign |
|
IGL02608:Lyst
|
APN |
13 |
13887339 |
missense |
probably damaging |
0.98 |
IGL02622:Lyst
|
APN |
13 |
13855975 |
missense |
probably damaging |
1.00 |
IGL02690:Lyst
|
APN |
13 |
13815710 |
missense |
possibly damaging |
0.58 |
IGL02715:Lyst
|
APN |
13 |
13848905 |
splice site |
probably null |
|
IGL02725:Lyst
|
APN |
13 |
13935412 |
missense |
probably damaging |
1.00 |
IGL02729:Lyst
|
APN |
13 |
13921194 |
missense |
possibly damaging |
0.95 |
IGL02729:Lyst
|
APN |
13 |
13848924 |
missense |
possibly damaging |
0.81 |
IGL02820:Lyst
|
APN |
13 |
13812643 |
missense |
probably benign |
0.03 |
IGL02945:Lyst
|
APN |
13 |
13935783 |
missense |
possibly damaging |
0.48 |
IGL02981:Lyst
|
APN |
13 |
13809496 |
missense |
probably damaging |
0.99 |
IGL03087:Lyst
|
APN |
13 |
13809641 |
missense |
probably damaging |
1.00 |
IGL03149:Lyst
|
APN |
13 |
13856029 |
missense |
probably benign |
0.14 |
IGL03158:Lyst
|
APN |
13 |
13826337 |
critical splice donor site |
probably null |
|
IGL03226:Lyst
|
APN |
13 |
13884144 |
missense |
probably benign |
0.01 |
IGL03242:Lyst
|
APN |
13 |
13831466 |
nonsense |
probably null |
|
IGL03385:Lyst
|
APN |
13 |
13831565 |
nonsense |
probably null |
|
charcoal
|
UTSW |
13 |
13871346 |
nonsense |
probably null |
|
charlotte_gray
|
UTSW |
13 |
13602026 |
intron |
probably benign |
|
charzard
|
UTSW |
13 |
13821668 |
nonsense |
probably null |
|
grey_wolf
|
UTSW |
13 |
|
unclassified |
|
|
lightspeed
|
UTSW |
13 |
13915121 |
missense |
possibly damaging |
0.91 |
pardon
|
UTSW |
13 |
13852537 |
missense |
probably benign |
0.00 |
robin
|
UTSW |
13 |
13823387 |
nonsense |
probably null |
|
sooty
|
UTSW |
13 |
|
unclassified |
|
|
souris
|
UTSW |
13 |
13857808 |
unclassified |
probably benign |
|
Swallow
|
UTSW |
13 |
13932007 |
missense |
probably benign |
0.00 |
vulpix
|
UTSW |
13 |
13871379 |
splice site |
probably null |
|
ANU22:Lyst
|
UTSW |
13 |
13852641 |
missense |
probably benign |
0.01 |
IGL02835:Lyst
|
UTSW |
13 |
13835685 |
missense |
possibly damaging |
0.82 |
P0031:Lyst
|
UTSW |
13 |
13838616 |
missense |
probably damaging |
1.00 |
R0012:Lyst
|
UTSW |
13 |
13862279 |
missense |
probably benign |
0.10 |
R0012:Lyst
|
UTSW |
13 |
13862279 |
missense |
probably benign |
0.10 |
R0031:Lyst
|
UTSW |
13 |
13882741 |
missense |
probably benign |
0.14 |
R0115:Lyst
|
UTSW |
13 |
13852537 |
missense |
probably benign |
0.00 |
R0212:Lyst
|
UTSW |
13 |
13810570 |
missense |
possibly damaging |
0.93 |
R0386:Lyst
|
UTSW |
13 |
13882799 |
splice site |
probably benign |
|
R0393:Lyst
|
UTSW |
13 |
13821664 |
missense |
probably benign |
0.01 |
R0415:Lyst
|
UTSW |
13 |
13886195 |
splice site |
probably benign |
|
R0446:Lyst
|
UTSW |
13 |
13812633 |
missense |
probably benign |
0.00 |
R0481:Lyst
|
UTSW |
13 |
13852537 |
missense |
probably benign |
0.00 |
R0499:Lyst
|
UTSW |
13 |
13791298 |
missense |
probably damaging |
1.00 |
R0506:Lyst
|
UTSW |
13 |
13812600 |
missense |
probably benign |
|
R0530:Lyst
|
UTSW |
13 |
13931891 |
splice site |
probably benign |
|
R0541:Lyst
|
UTSW |
13 |
13855878 |
missense |
probably benign |
0.00 |
R0570:Lyst
|
UTSW |
13 |
13883971 |
missense |
probably benign |
0.26 |
R0680:Lyst
|
UTSW |
13 |
13824926 |
missense |
probably benign |
0.01 |
R0842:Lyst
|
UTSW |
13 |
13852826 |
nonsense |
probably null |
|
R0848:Lyst
|
UTSW |
13 |
13809515 |
missense |
probably benign |
0.00 |
R1014:Lyst
|
UTSW |
13 |
13808645 |
missense |
possibly damaging |
0.49 |
R1205:Lyst
|
UTSW |
13 |
13854787 |
missense |
probably benign |
|
R1251:Lyst
|
UTSW |
13 |
13809068 |
missense |
probably benign |
0.00 |
R1304:Lyst
|
UTSW |
13 |
13926569 |
nonsense |
probably null |
|
R1398:Lyst
|
UTSW |
13 |
13915121 |
missense |
possibly damaging |
0.91 |
R1445:Lyst
|
UTSW |
13 |
13814639 |
missense |
possibly damaging |
0.94 |
R1475:Lyst
|
UTSW |
13 |
13882797 |
critical splice donor site |
probably null |
|
R1479:Lyst
|
UTSW |
13 |
13809067 |
missense |
probably benign |
0.00 |
R1484:Lyst
|
UTSW |
13 |
13852775 |
missense |
probably benign |
0.01 |
R1498:Lyst
|
UTSW |
13 |
13824960 |
missense |
possibly damaging |
0.49 |
R1540:Lyst
|
UTSW |
13 |
13809686 |
missense |
possibly damaging |
0.81 |
R1611:Lyst
|
UTSW |
13 |
13809482 |
missense |
probably damaging |
0.97 |
R1653:Lyst
|
UTSW |
13 |
13809811 |
missense |
probably damaging |
1.00 |
R1669:Lyst
|
UTSW |
13 |
13818672 |
missense |
possibly damaging |
0.90 |
R1686:Lyst
|
UTSW |
13 |
13809290 |
missense |
possibly damaging |
0.81 |
R1694:Lyst
|
UTSW |
13 |
13835746 |
missense |
probably damaging |
0.98 |
R1747:Lyst
|
UTSW |
13 |
13932007 |
missense |
probably benign |
0.00 |
R1793:Lyst
|
UTSW |
13 |
13821668 |
nonsense |
probably null |
|
R1871:Lyst
|
UTSW |
13 |
13826297 |
missense |
probably benign |
0.00 |
R1905:Lyst
|
UTSW |
13 |
13808719 |
missense |
probably benign |
|
R1958:Lyst
|
UTSW |
13 |
13791203 |
missense |
probably damaging |
1.00 |
R1969:Lyst
|
UTSW |
13 |
13904929 |
missense |
probably damaging |
0.99 |
R2040:Lyst
|
UTSW |
13 |
13815807 |
missense |
probably benign |
0.00 |
R2109:Lyst
|
UTSW |
13 |
13887405 |
missense |
possibly damaging |
0.46 |
R2116:Lyst
|
UTSW |
13 |
13810286 |
missense |
probably damaging |
0.99 |
R2121:Lyst
|
UTSW |
13 |
13835556 |
missense |
probably damaging |
1.00 |
R2127:Lyst
|
UTSW |
13 |
13809847 |
missense |
probably damaging |
1.00 |
R2187:Lyst
|
UTSW |
13 |
13883926 |
missense |
possibly damaging |
0.61 |
R2238:Lyst
|
UTSW |
13 |
13917848 |
missense |
probably benign |
0.41 |
R2258:Lyst
|
UTSW |
13 |
13812243 |
missense |
probably benign |
0.00 |
R2292:Lyst
|
UTSW |
13 |
13915080 |
missense |
probably damaging |
1.00 |
R2368:Lyst
|
UTSW |
13 |
13871248 |
missense |
probably damaging |
0.96 |
R2908:Lyst
|
UTSW |
13 |
13844458 |
missense |
probably benign |
0.03 |
R3001:Lyst
|
UTSW |
13 |
13871290 |
missense |
probably benign |
|
R3002:Lyst
|
UTSW |
13 |
13871290 |
missense |
probably benign |
|
R3024:Lyst
|
UTSW |
13 |
13833272 |
missense |
probably benign |
|
R3113:Lyst
|
UTSW |
13 |
13844512 |
missense |
probably benign |
0.12 |
R3406:Lyst
|
UTSW |
13 |
13809815 |
missense |
possibly damaging |
0.56 |
R3972:Lyst
|
UTSW |
13 |
13881210 |
missense |
possibly damaging |
0.67 |
R3978:Lyst
|
UTSW |
13 |
13808753 |
missense |
possibly damaging |
0.82 |
R4032:Lyst
|
UTSW |
13 |
13791250 |
missense |
probably damaging |
1.00 |
R4192:Lyst
|
UTSW |
13 |
13915098 |
missense |
probably damaging |
1.00 |
R4206:Lyst
|
UTSW |
13 |
13810574 |
missense |
probably benign |
0.03 |
R4298:Lyst
|
UTSW |
13 |
13809472 |
missense |
probably damaging |
1.00 |
R4344:Lyst
|
UTSW |
13 |
13873051 |
missense |
probably benign |
0.06 |
R4441:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4445:Lyst
|
UTSW |
13 |
13884149 |
missense |
probably benign |
0.42 |
R4477:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4493:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4494:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4495:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4622:Lyst
|
UTSW |
13 |
13848983 |
missense |
probably benign |
0.01 |
R4638:Lyst
|
UTSW |
13 |
13871379 |
splice site |
probably null |
|
R4658:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4675:Lyst
|
UTSW |
13 |
13809968 |
missense |
probably damaging |
1.00 |
R4719:Lyst
|
UTSW |
13 |
13824935 |
missense |
probably benign |
|
R4729:Lyst
|
UTSW |
13 |
13812486 |
missense |
probably damaging |
1.00 |
R4774:Lyst
|
UTSW |
13 |
13915182 |
missense |
probably damaging |
1.00 |
R4811:Lyst
|
UTSW |
13 |
13951685 |
missense |
probably benign |
0.33 |
R4877:Lyst
|
UTSW |
13 |
13857734 |
missense |
probably damaging |
1.00 |
R4920:Lyst
|
UTSW |
13 |
13821645 |
missense |
possibly damaging |
0.79 |
R4933:Lyst
|
UTSW |
13 |
13933963 |
missense |
probably benign |
0.12 |
R4933:Lyst
|
UTSW |
13 |
13812349 |
missense |
probably damaging |
0.98 |
R4958:Lyst
|
UTSW |
13 |
13810048 |
missense |
probably benign |
0.00 |
R4982:Lyst
|
UTSW |
13 |
13900539 |
missense |
probably damaging |
1.00 |
R4992:Lyst
|
UTSW |
13 |
13835748 |
missense |
probably damaging |
1.00 |
R5024:Lyst
|
UTSW |
13 |
13808989 |
missense |
probably benign |
|
R5049:Lyst
|
UTSW |
13 |
13810649 |
missense |
probably damaging |
1.00 |
R5079:Lyst
|
UTSW |
13 |
13931938 |
missense |
probably benign |
0.08 |
R5254:Lyst
|
UTSW |
13 |
13857655 |
missense |
probably benign |
0.00 |
R5266:Lyst
|
UTSW |
13 |
13835555 |
missense |
probably damaging |
1.00 |
R5279:Lyst
|
UTSW |
13 |
13823387 |
nonsense |
probably null |
|
R5285:Lyst
|
UTSW |
13 |
13809011 |
missense |
probably benign |
0.01 |
R5364:Lyst
|
UTSW |
13 |
13831439 |
missense |
probably benign |
0.35 |
R5435:Lyst
|
UTSW |
13 |
13951649 |
missense |
possibly damaging |
0.64 |
R5516:Lyst
|
UTSW |
13 |
13818707 |
missense |
probably benign |
0.10 |
R5524:Lyst
|
UTSW |
13 |
13921364 |
missense |
probably benign |
0.03 |
R5591:Lyst
|
UTSW |
13 |
13917918 |
missense |
probably damaging |
0.99 |
R5592:Lyst
|
UTSW |
13 |
13917918 |
missense |
probably damaging |
0.99 |
R5593:Lyst
|
UTSW |
13 |
13917918 |
missense |
probably damaging |
0.99 |
R5594:Lyst
|
UTSW |
13 |
13917918 |
missense |
probably damaging |
0.99 |
R5594:Lyst
|
UTSW |
13 |
13933982 |
missense |
probably benign |
0.00 |
R5644:Lyst
|
UTSW |
13 |
13812081 |
missense |
possibly damaging |
0.58 |
R5659:Lyst
|
UTSW |
13 |
13809212 |
missense |
possibly damaging |
0.58 |
R5741:Lyst
|
UTSW |
13 |
13808615 |
missense |
probably benign |
0.44 |
R5908:Lyst
|
UTSW |
13 |
13871346 |
nonsense |
probably null |
|
R5969:Lyst
|
UTSW |
13 |
13862398 |
splice site |
probably null |
|
R6128:Lyst
|
UTSW |
13 |
13933964 |
missense |
possibly damaging |
0.67 |
R6271:Lyst
|
UTSW |
13 |
13833339 |
missense |
probably benign |
0.30 |
R6315:Lyst
|
UTSW |
13 |
13818089 |
missense |
probably benign |
|
R6318:Lyst
|
UTSW |
13 |
13917896 |
missense |
possibly damaging |
0.88 |
R6555:Lyst
|
UTSW |
13 |
13823510 |
missense |
probably benign |
0.01 |
R6663:Lyst
|
UTSW |
13 |
13838701 |
splice site |
probably null |
|
R6701:Lyst
|
UTSW |
13 |
13856070 |
missense |
probably benign |
0.06 |
R6711:Lyst
|
UTSW |
13 |
13809820 |
missense |
possibly damaging |
0.80 |
R6909:Lyst
|
UTSW |
13 |
13917960 |
missense |
probably damaging |
1.00 |
R6915:Lyst
|
UTSW |
13 |
13900629 |
missense |
probably benign |
0.01 |
R6929:Lyst
|
UTSW |
13 |
13917909 |
missense |
probably damaging |
1.00 |
R6960:Lyst
|
UTSW |
13 |
13808663 |
missense |
probably benign |
0.12 |
R7018:Lyst
|
UTSW |
13 |
13918044 |
critical splice donor site |
probably null |
|
R7037:Lyst
|
UTSW |
13 |
13791251 |
missense |
probably damaging |
1.00 |
R7045:Lyst
|
UTSW |
13 |
13812293 |
missense |
probably damaging |
1.00 |
R7045:Lyst
|
UTSW |
13 |
13809485 |
missense |
probably benign |
0.34 |
R7070:Lyst
|
UTSW |
13 |
13932029 |
missense |
probably benign |
0.23 |
R7188:Lyst
|
UTSW |
13 |
13926675 |
missense |
possibly damaging |
0.66 |
R7201:Lyst
|
UTSW |
13 |
13883885 |
nonsense |
probably null |
|
R7210:Lyst
|
UTSW |
13 |
13831568 |
missense |
probably damaging |
1.00 |
R7229:Lyst
|
UTSW |
13 |
13818094 |
missense |
probably benign |
0.00 |
R7293:Lyst
|
UTSW |
13 |
13854822 |
missense |
probably benign |
0.01 |
R7318:Lyst
|
UTSW |
13 |
13932028 |
missense |
probably benign |
0.13 |
R7344:Lyst
|
UTSW |
13 |
13881140 |
missense |
probably benign |
|
R7426:Lyst
|
UTSW |
13 |
13812109 |
missense |
probably benign |
|
R7522:Lyst
|
UTSW |
13 |
13821668 |
nonsense |
probably null |
|
R7583:Lyst
|
UTSW |
13 |
13810472 |
missense |
probably damaging |
1.00 |
R7606:Lyst
|
UTSW |
13 |
13812060 |
missense |
probably damaging |
1.00 |
R7636:Lyst
|
UTSW |
13 |
13791332 |
critical splice donor site |
probably null |
|
R7658:Lyst
|
UTSW |
13 |
13905061 |
missense |
possibly damaging |
0.63 |
R7685:Lyst
|
UTSW |
13 |
13844450 |
missense |
probably benign |
0.00 |
R7689:Lyst
|
UTSW |
13 |
13857808 |
critical splice donor site |
probably null |
|
R7765:Lyst
|
UTSW |
13 |
13884117 |
missense |
possibly damaging |
0.75 |
R7779:Lyst
|
UTSW |
13 |
13809128 |
missense |
probably damaging |
1.00 |
R7871:Lyst
|
UTSW |
13 |
13810637 |
nonsense |
probably null |
|
R7872:Lyst
|
UTSW |
13 |
13810450 |
missense |
probably benign |
0.14 |
R7884:Lyst
|
UTSW |
13 |
13882268 |
missense |
probably benign |
0.09 |
R7890:Lyst
|
UTSW |
13 |
13915154 |
missense |
probably damaging |
0.99 |
R7916:Lyst
|
UTSW |
13 |
13821657 |
missense |
possibly damaging |
0.64 |
R7948:Lyst
|
UTSW |
13 |
13921174 |
missense |
possibly damaging |
0.59 |
R7956:Lyst
|
UTSW |
13 |
13815788 |
missense |
possibly damaging |
0.80 |
R8048:Lyst
|
UTSW |
13 |
13862230 |
missense |
probably benign |
0.12 |
R8085:Lyst
|
UTSW |
13 |
13808894 |
missense |
probably damaging |
0.98 |
R8165:Lyst
|
UTSW |
13 |
13872945 |
missense |
probably damaging |
0.99 |
R8235:Lyst
|
UTSW |
13 |
13935323 |
missense |
possibly damaging |
0.69 |
R8237:Lyst
|
UTSW |
13 |
13826317 |
missense |
probably benign |
0.00 |
R8275:Lyst
|
UTSW |
13 |
13950667 |
missense |
probably benign |
0.02 |
R8300:Lyst
|
UTSW |
13 |
13838643 |
missense |
possibly damaging |
0.79 |
R8350:Lyst
|
UTSW |
13 |
13824973 |
nonsense |
probably null |
|
R8526:Lyst
|
UTSW |
13 |
13935391 |
missense |
probably damaging |
0.99 |
R8551:Lyst
|
UTSW |
13 |
13808645 |
missense |
possibly damaging |
0.77 |
R8723:Lyst
|
UTSW |
13 |
13887342 |
missense |
possibly damaging |
0.89 |
R8772:Lyst
|
UTSW |
13 |
13812077 |
nonsense |
probably null |
|
R8778:Lyst
|
UTSW |
13 |
13903152 |
missense |
possibly damaging |
0.89 |
R8778:Lyst
|
UTSW |
13 |
13810361 |
missense |
possibly damaging |
0.89 |
R8801:Lyst
|
UTSW |
13 |
13835595 |
missense |
probably benign |
0.10 |
R8837:Lyst
|
UTSW |
13 |
13852548 |
missense |
probably benign |
|
R8874:Lyst
|
UTSW |
13 |
13812147 |
missense |
probably benign |
|
R8878:Lyst
|
UTSW |
13 |
13815661 |
missense |
probably benign |
0.00 |
R8891:Lyst
|
UTSW |
13 |
13887435 |
missense |
possibly damaging |
0.67 |
R9077:Lyst
|
UTSW |
13 |
13857693 |
missense |
probably benign |
0.02 |
R9127:Lyst
|
UTSW |
13 |
13808827 |
missense |
probably damaging |
1.00 |
R9143:Lyst
|
UTSW |
13 |
13835750 |
missense |
probably damaging |
0.98 |
R9216:Lyst
|
UTSW |
13 |
13823188 |
missense |
probably benign |
|
R9217:Lyst
|
UTSW |
13 |
13871245 |
missense |
probably benign |
0.01 |
R9291:Lyst
|
UTSW |
13 |
13883938 |
missense |
probably benign |
0.01 |
R9302:Lyst
|
UTSW |
13 |
13904947 |
missense |
possibly damaging |
0.46 |
R9370:Lyst
|
UTSW |
13 |
13935333 |
missense |
probably damaging |
1.00 |
R9402:Lyst
|
UTSW |
13 |
13812463 |
missense |
probably benign |
|
R9457:Lyst
|
UTSW |
13 |
13862330 |
missense |
possibly damaging |
0.83 |
R9481:Lyst
|
UTSW |
13 |
13857653 |
missense |
possibly damaging |
0.68 |
R9563:Lyst
|
UTSW |
13 |
13812408 |
missense |
probably benign |
0.36 |
R9623:Lyst
|
UTSW |
13 |
13852587 |
missense |
probably benign |
|
R9661:Lyst
|
UTSW |
13 |
13808779 |
missense |
probably benign |
0.01 |
R9682:Lyst
|
UTSW |
13 |
13831526 |
missense |
probably benign |
0.21 |
R9743:Lyst
|
UTSW |
13 |
13809323 |
missense |
possibly damaging |
0.67 |
R9801:Lyst
|
UTSW |
13 |
13809290 |
missense |
probably damaging |
0.97 |
RF001:Lyst
|
UTSW |
13 |
13810426 |
missense |
probably benign |
|
RF002:Lyst
|
UTSW |
13 |
13808948 |
missense |
probably benign |
0.05 |
X0024:Lyst
|
UTSW |
13 |
13809033 |
missense |
probably benign |
0.00 |
X0026:Lyst
|
UTSW |
13 |
13926555 |
missense |
probably damaging |
0.99 |
Z1088:Lyst
|
UTSW |
13 |
13918018 |
missense |
probably benign |
0.09 |
Z1176:Lyst
|
UTSW |
13 |
13951664 |
missense |
probably benign |
0.27 |
Z1176:Lyst
|
UTSW |
13 |
13814692 |
missense |
probably damaging |
1.00 |
Z1177:Lyst
|
UTSW |
13 |
13854719 |
missense |
possibly damaging |
0.73 |
|
Mode of Inheritance |
Autosomal Recessive |
Local Stock | |
Repository | None
|
Last Updated |
2019-10-14 8:42 PM
by Diantha La Vine
|
Record Created |
2014-09-10 2:12 PM
by Carlos Reyna
|
Record Posted |
2015-02-05 |
Phenotypic Description |
The 50-cal phenotype was identified among ENU-induced G3 mice of the pedigree R1475, some of which had a dark grey coat color (Figure 1). Some mice also showed increased mouse cytomegalovirus (MCMV) titers in the spleen (Figure 2) and liver (Figure 3) after MCMV infection.
|
Nature of Mutation |
Whole exome HiSeq sequencing of the G1 grandsire identified 54 mutations. The increased susceptibility to MCMV infection phenotype was linked by continuous variable mapping to a mutation in Lyst. The Lyst mutation is a T to A transversion at base pair 13,708,212 (v38) on chromosome 13, or base pair 117,881 in the GenBank genomic region NC_000079 within the donor splice site of intron 34. The strongest association was found with a recessive model of linkage to the normalized MCMV titer in the spleen, wherein 1 variant homozygote departed phenotypically from 10 homozygous reference mice and 9 heterozygous mice with a P value of 5.221 x 10-50 (Figure 4). The effect of the mutation at the cDNA and protein level have not examined, but the mutation is predicted to result in skipping of the 189-nucleotide exon 34 (out of 53 total exons), resulting in coding of one aberrant amino acid (S2857R); the rest of the protein product is unchanged.
<--exon 33 <--exon 34 intron 34--> exon 35-->
8735 ……AACAACAACCAGCAAAG ……CAGCTGACACATGACAG gtgtgcagtgggaac…… AGCAGTCTGGTATGAC……
2852 ……-N--N--N--Q--Q--S ……-Q--L--T--H--D--R --A--V--W--Y--D-……
correct deleted correct
|
The donor splice site of intron 34, which is destroyed by the 50-cal mutation, is indicated in blue lettering and the mutated nucleotide is indicated in red. The highlighted amino acid (S2857) is aberrant as the result of the mutation. Alternatively, the use of a cryptic site in exon 34 may be used resulting in deletion of 89 nucleotides in exon 34. The deletion would result in a frameshift, coding of four aberrant amino acids after amino acid 2890, and coding of a premature stop codon after amino acid 2894.
<--exon 33 <--exon 34 intron 34--> exon 35-->
8735 ……AACAACAACCAGCAAAG ……AAGGAAGAAGGTGATCCAGC……CAGCTGACACATGACAG gtgtgcagtgggaac…… AGCAGTCTGGTATGA
2852 ……-N--N--N--Q--Q--S ……--R--K--K--V--I--Q--……-Q--L--T--H--D--R -S--S--L--V--*
correct deleted aberrant
|
The donor splice site of intron 34, which is destroyed by the 50-cal mutation, is indicated in blue lettering and the mutated nucleotide is indicated in red. The putative cryptic splice donor site is highlighted.
|
Illustration of Mutations in
Gene & Protein |
|
---|
Protein Prediction |
The Lyst gene encodes the protein Lyst (also CHS/Beige), a 3788-amino acid protein whose biochemical functions remain unknown (Figure 3). A large N-terminal portion of the protein (amino acids 1-3132) contains approximately twenty repeats with homology to ARM (Armadillo) and HEAT (huntingtin, elongation factor 3, A subunit of protein phosphatase A, target of rapamycin) repeat motifs (1;2). ARM and HEAT motifs are α-helical domains of about 50 amino acids that pack together to form elongated “solenoids” (3); evidence suggests they mediate protein associations at the membrane (4), and vesicle transport (5), respectively. The C-terminus of Lyst contains two distinct domains, a BEACH (beige and chediak) domain (amino acids 3132-3472) and seven WD40 motifs (1). The BEACH domain is a 345-amino acid region of unknown function (1), and WD40 motifs are protein interaction motifs that typically form β sheets arranged in a 7-bladed β propeller fold (6).The 50-cal mutation is predicted to affect the ARM/HEAT domain. Please see the record for souris for information about Lyst.
|
Putative Mechanism | In humans, mutations in the LYST gene cause Chediak-Higashi Syndrome (CHS, OMIM #214500), a rare autosomal recessive disorder characterized by oculocutaneous albinism, severe immune deficiency, bleeding tendency, recurrent pyogenic infection, progressive neurologic defects and a lymphoproliferative syndrome [(7;8); reviewed in (2)]. These defects are caused by the aberrant formation of giant granules within a variety of cell types, and disrupted intracellular protein trafficking (2;9;10). The enlarged granules consist of organelles such as lysosomes, melanosomes, cytolytic granules and platelet dense bodies, and it is thought that the increased size of these organelles inhibits their migration and fusion at the cell surface and/or organelle-organelle fusion. There is no clear understanding of the molecular mechanisms of Lyst protein function, or how its loss leads to the formation of enlarged lysosomes and lysosome-related organelles. In mice, mutations in Lyst cause the beige phenotype (7;8). As in humans, beige mice exhibit hypopigmentation, bleeding tendency, and defective immune cell function resulting from the formation of giant granules in melanosomes, lymphocytes, neutrophils, and other cell types (10-12). Beige mice have defective NK cell (13) and cytotoxic T lymphocyte function (14), and increased susceptibility to infections including MCMV (15;16). However, beige mice do not develop lymphoproliferative disorder, even after challenge with infection (15). The 50-cal hypopigmentation and MCMV susceptibility phenotype mimics other known alleles of Lyst (see MGI for a list of Lyst alleles as well as the Beutler alleles souris and charlotte_gray) indicating that there is loss of function in the Lyst50-cal protein.
|
Primers |
PCR Primer
50-cal_pcr_F: GTATGCTGGAGACGGTACTCAGG
50-cal_pcr_R: ACCCTCTCCTCTCCAGGTATGTC
Sequencing Primer
50-cal_seq_F: GGTTCTCCAGCATGCTAGTC
50-cal_seq_R: GTCTGAGGACAGTTACAGTG
|
Genotyping | PCR program 1) 94°C 2:00 2) 94°C 0:30 3) 55°C 0:30 4) 72°C 1:00 5) repeat steps (2-4) 40x 6) 72°C 10:00 7) 4°C hold
The following sequence of 494 nucleotides is amplified (chromosome 13, + strand):
1 gtatgctgga gacggtactc aggttctcca gcatgctagt caaatgctat accactgagc 61 tgtatcccag cctgaggtgt actgttcaga tacttaatgt ttagtgaata cttaactttg 121 gaacaatctt gttggtttag tctcttccag aggctcgatt tcaaatccaa ggatatatct 181 aaaatcgctg cagacatcac ccaggctgta tcactctccc aaggcattga aaggaagaag 241 gtgatccagc acatcagagg gatgtacaaa gttgacctga gtgccagcag gcactggcag 301 gaatgcatcc agcagctgac acatgacagg tgtgcagtgg gaacacgtgg ctgagcacag 361 cttctatatg tgatgtgtaa tagtgttttc attccagtac tcacatttat acaattattt 421 ttttaaaaga tttatttatt gttatatgta agtacactgt aactgtcctc agacatacct 481 ggagaggaga gggt
Primer binding sites are underlined and the sequencing primers are highlighted; the mutated nucleotide is shown in red. |
References | 1. Nagle, D. L., Karim, M. A., Woolf, E. A., Holmgren, L., Bork, P., Misumi, D. J., McGrail, S. H., Dussault, B. J.,Jr, Perou, C. M., Boissy, R. E., Duyk, G. M., Spritz, R. A., and Moore, K. J. (1996) Identification and Mutation Analysis of the Complete Gene for Chediak-Higashi Syndrome. Nat Genet. 14, 307-311.
3. Andrade, M. A., Petosa, C., O'Donoghue, S. I., Muller, C. W., and Bork, P. (2001) Comparison of ARM and HEAT Protein Repeats. J Mol Biol. 309, 1-18.
6. Sondek, J., Bohm, A., Lambright, D. G., Hamm, H. E., and Sigler, P. B. (1996) Crystal Structure of a G-Protein Beta Gamma Dimer at 2.1A Resolution. Nature. 379, 369-374.
7. Barbosa, M. D., Nguyen, Q. A., Tchernev, V. T., Ashley, J. A., Detter, J. C., Blaydes, S. M., Brandt, S. J., Chotai, D., Hodgman, C., Solari, R. C., Lovett, M., and Kingsmore, S. F. (1996) Identification of the Homologous Beige and Chediak-Higashi Syndrome Genes. Nature. 382, 262-265.
8. Perou, C. M., Moore, K. J., Nagle, D. L., Misumi, D. J., Woolf, E. A., McGrail, S. H., Holmgren, L., Brody, T. H., Dussault, B. J.,Jr., Monroe, C. A., Duyk, G. M., Pryor, R. J., Li, L., Justice, M. J., and Kaplan, J. (1996) Identification of the Murine Beige Gene by YAC Complementation and Positional Cloning. Nat Genet. 13, 303-308.
9. Faigle, W., Raposo, G., Tenza, D., Pinet, V., Vogt, A. B., Kropshofer, H., Fischer, A., de Saint-Basile, G., and Amigorena, S. (1998) Deficient Peptide Loading and MHC Class II Endosomal Sorting in a Human Genetic Immunodeficiency Disease: The Chediak-Higashi Syndrome. J Cell Biol. 141, 1121-1134.
11. Kelly, E. M. (1957) Beige, Bg. Mouse News Lett. 16, 36-36.
|
Science Writers | Anne Murray |
Illustrators | Katherine Timer |
Authors | Tao Yue, Duanwu Zhang, Carlos Reyna, Tiana Purrington, Bruce Beutler |