Phenotypic Mutation 'Swallow' (pdf version)
Allele | Swallow |
Mutation Type |
missense
|
Chromosome | 13 |
Coordinate | 13,932,007 bp (GRCm39) |
Base Change | T ⇒ C (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_010748.2; MGI:107448
|
Mapped | Yes |
Amino Acid Change |
Phenylalanine changed to Serine
|
Institutional Source | Beutler Lab |
Gene Model |
predicted gene model for protein(s):
[ENSMUSP00000106188]
|
AlphaFold |
no structure available at present |
SMART Domains |
Protein: ENSMUSP00000106188 Gene: ENSMUSG00000019726 AA Change: F3545S
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 benign
PolyPhen 2
Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
(Using ENSMUST00000110559)
|
Meta Mutation Damage Score |
0.1680 |
Is this an essential gene? |
Possibly nonessential (E-score: 0.414) |
Phenotypic Category |
Autosomal Semidominant |
Candidate Explorer Status |
loading ... |
Single pedigree Linkage Analysis Data
|
|
Penetrance | |
Alleles Listed at MGI | All mutations/alleles(54) : Chemically induced (ENU)(7) 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 |
|
50-cal
|
UTSW |
13 |
13882797 |
critical splice donor site |
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 |
|
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 Semidominant |
Local Stock | |
MMRRC Submission |
038166-MU
|
Last Updated |
2019-09-04 9:46 PM
by Diantha La Vine
|
Record Created |
2015-01-20 6:40 PM
by Zhao Zhang
|
Record Posted |
2015-02-12 |
Phenotypic Description |
The Swallow phenotype was identified among N-Nitroso-N-ethylurea (ENU)-mutagenized G3 mice of the pedigree R1747, some of which showed an increased rate of phagocytosis in peritoneal exudate cells (PECs; Figure 1). Phagocytosis was detected by measuring the fluorescence intensity of pHrodo® Green E. coli conjugates two hours after treatment of PECs with an experimental phagocytosis effector (e.g., Cytochalasin D). The pHrodo® Green E. coli conjugates fluoresce at acidic pH, such as in phagosomes. Some mice also exhibited hypopigmentation.
|
Nature of Mutation |
Whole exome HiSeq sequencing of the G1 grandsire identified 65 mutations. The increased rate of PEC phagocytosis was linked by continuous variable mapping to a mutation in Lyst: a T to C transition at base pair 13,757,422 (v38) on chromosome 13, or base pair 167,091 in the GenBank genomic region NC_000079 encoding Lyst. Linkage was found with an additive model of inheritance (P = 2.769 x 10-7), wherein 8 variant homozygotes and 8 heterozygotes departed phenotypically from 4 homozygous reference mice (Figure 2). The mutation corresponds to residue 10,815 in the mRNA sequence NM_010748.2 within exon 47 of 53 total exons.
10799 GAGCCACCAATCAACTTCATTCAGAGTTCACAG
3540 -E--P--P--I--N--F--I--Q--S--S--Q-
|
The mutated nucleotide is indicated in red. The mutation results in a phenylalanine (F) to serine (S) substitution at position 3545 (F3545S) in the Lyst protein, and is strongly predicted by Polyphen-2 to be benign (score = 0.004).
|
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 2). 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 Swallow mutation is predicted to affect the first WD40 motif. 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). Defective lysosome-related functions in immune cells lead to immune deficiency, recurrent bacterial infections and lymphoproliferative disorder in CHS patients. 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 (CTL) function (14), and increased susceptibility to infections (15;16). CHS macrophages and polymorphonuclear leukocytes have normal phagocytic ability, but delayed fusion of phagosomes with lysosomes, allowing bacterial replication and escape and leading to persistent infections (2). The increased fluorescence intensity observed in the Swallow PECs indicates that phagocytosis is occuring and, similar to patients with CHS, that the fusion between the phagosomes and lysosomes may be delayed leading to protein accumulation within the phagosome.
|
Primers |
PCR Primer
Swallow_pcr_F: TTAGGAAGGGATGGCTTCTCCCAG
Swallow_pcr_R: GCAAGCTCTCCCAATGAGGAAGTAG
Sequencing Primer
Swallow_seq_F: CCAGCAGAGTTTACTTCCAGTG
Swallow_seq_R: CCGTGGGACCTAATCAGATG
|
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 719 nucleotides is amplified (chromosome 13, + strand):
1 ttaggaaggg atggcttctc ccagcagagt ttacttccag tgttcaaagt tgttcatact 61 gactactcag cactagatat caagaacgtt acttaacaag tatttaggtc atgtttcact 121 tttaaagaaa aagaatctca gagcacgaat agagtaagct ttattattgt tgttgtcttt 181 ataaaatttt atctgagaag ataattccac ccttaggact aaaactaaga ttattttatc 241 tcagacagat aaggacatag tgcctgaaaa gagtgtatat tctgctttat aaatgtcagc 301 ctttaccttg ctcttgtctg aggtgttata tgatactata ctgacaacta gatccttggt 361 tttcccttct gttgaggtgt gagaagcatg aacaacacca atattcagtg gtctgctatc 421 ctaagctggg gatatgctga caacatctta cggttgaaaa gtaagcagag tgagccacca 481 atcaacttca ttcagagttc acagcagcac caggtaagct taggtataag gactgtatgc 541 tgatgaagtt ccatgtcttg cgaaggaagg aaggaaggaa ggaatctagc taacactggt 601 ctacttaaat gtcagcccag aagctgctgt ttgcagagct tctaggtgtc ataatccctg 661 ctcatctgat taggtcccac ggtttgattt ttgcctactt cctcattggg agagcttgc
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., Barrat, F. J., Tchernev, V. T., Nguyen, Q. A., Mishra, V. S., Colman, S. D., Pastural, E., Dufourcq-Lagelouse, R., Fischer, A., Holcombe, R. F., Wallace, M. R., Brandt, S. J., de Saint, B. G., and Kingsmore, S. F. (1997) Identification of Mutations in Two Major mRNA Isoforms of the Chediak-Higashi Syndrome Gene in Human and Mouse. Hum Mol Genet. 6, 1091-1098.
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 | Peter Jurek, Katherine Timer |
Authors | Zhao Zhang, Ying Wang, Hexin Shi, Doan Dao, Lei Sun, Bruce Beutler |