Incidental Mutation 'R0546:Aass'
| ID |
44822 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Aass
|
| Ensembl Gene |
ENSMUSG00000029695 |
| Gene Name |
aminoadipate-semialdehyde synthase |
| Synonyms |
LOR/SDH, Lorsdh |
| MMRRC Submission |
038738-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R0546 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
6 |
| Chromosomal Location |
23072172-23132985 bp(-) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
A to G
at 23077076 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000031707
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000031707]
|
| AlphaFold |
Q99K67 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000031707
|
| SMART Domains |
Protein: ENSMUSP00000031707
Gene: ENSMUSG00000029695
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
2 |
20 |
N/A |
INTRINSIC |
|
AlaDh_PNT_N
|
27 |
157 |
2.76e-22 |
SMART |
|
AlaDh_PNT_C
|
197 |
399 |
7.94e-23 |
SMART |
|
Pfam:Sacchrp_dh_NADP
|
483 |
598 |
2.8e-26 |
PFAM |
|
Pfam:Sacchrp_dh_C
|
602 |
916 |
1.2e-88 |
PFAM |
|
| Meta Mutation Damage Score |
0.9481 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.7%
- 10x: 97.1%
- 20x: 95.0%
|
| Validation Efficiency |
99% (74/75) |
| MGI Phenotype |
FUNCTION: This gene encodes a bifunctional mitochondrial protein that catalyzes the first two steps in the lysine degradation pathway. The N-terminus contains lysine-ketoglutarate reductase activity and converts lysine to saccharopine, whereas the C-terminus contains saccharopine dehydrogenase activity and converts saccharopine to alpha-aminoadipate semialdehyde. Mutations in a human gene encoding a highly similar protein are associated with familial hyperlysinemia. [provided by RefSeq, Jul 2008]
|
| Allele List at MGI |
All alleles(10) : Targeted(2) Gene trapped(8)
|
| Other mutations in this stock |
Total: 75 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Actn1 |
C |
T |
12: 80,225,208 (GRCm39) |
R418Q |
probably benign |
Het |
| Adam39 |
G |
A |
8: 41,279,468 (GRCm39) |
V620M |
probably damaging |
Het |
| Agr3 |
C |
A |
12: 35,978,329 (GRCm39) |
T14K |
probably benign |
Het |
| Alpk2 |
T |
C |
18: 65,439,788 (GRCm39) |
D1002G |
probably benign |
Het |
| Amz2 |
T |
A |
11: 109,324,780 (GRCm39) |
N221K |
probably benign |
Het |
| Aox4 |
A |
G |
1: 58,289,333 (GRCm39) |
E752G |
probably damaging |
Het |
| Ap2a1 |
C |
T |
7: 44,554,132 (GRCm39) |
G500S |
probably damaging |
Het |
| Car5b |
G |
A |
X: 162,762,297 (GRCm39) |
R282C |
probably damaging |
Het |
| Ccdc112 |
A |
G |
18: 46,424,139 (GRCm39) |
S200P |
possibly damaging |
Het |
| Ccdc18 |
A |
T |
5: 108,322,830 (GRCm39) |
E643D |
probably benign |
Het |
| Ccdc180 |
A |
T |
4: 45,904,597 (GRCm39) |
T398S |
possibly damaging |
Het |
| Cnp |
A |
G |
11: 100,471,549 (GRCm39) |
Y397C |
probably damaging |
Het |
| Cpa4 |
T |
C |
6: 30,580,962 (GRCm39) |
W184R |
probably damaging |
Het |
| Crebbp |
A |
T |
16: 3,903,671 (GRCm39) |
I1856N |
probably damaging |
Het |
| Ctrl |
A |
G |
8: 106,658,966 (GRCm39) |
I200T |
probably damaging |
Het |
| Cyfip1 |
C |
T |
7: 55,572,564 (GRCm39) |
R934* |
probably null |
Het |
| Dennd5a |
A |
G |
7: 109,520,633 (GRCm39) |
V408A |
probably benign |
Het |
| Dhfr |
G |
A |
13: 92,504,692 (GRCm39) |
|
probably null |
Het |
| Dnajc6 |
A |
T |
4: 101,492,388 (GRCm39) |
N740Y |
probably damaging |
Het |
| Fam110a |
T |
C |
2: 151,812,732 (GRCm39) |
T13A |
probably benign |
Het |
| Fars2 |
G |
T |
13: 36,388,569 (GRCm39) |
K19N |
probably benign |
Het |
| Fer1l6 |
A |
T |
15: 58,430,257 (GRCm39) |
|
probably null |
Het |
| Gabra1 |
T |
A |
11: 42,053,428 (GRCm39) |
T69S |
probably damaging |
Het |
| Galnt18 |
T |
G |
7: 111,107,348 (GRCm39) |
N475T |
probably damaging |
Het |
| Gbp4 |
T |
C |
5: 105,268,836 (GRCm39) |
Y439C |
probably damaging |
Het |
| Gpatch2l |
A |
G |
12: 86,335,622 (GRCm39) |
*409W |
probably null |
Het |
| Hip1r |
T |
C |
5: 124,137,114 (GRCm39) |
V658A |
possibly damaging |
Het |
| Hspg2 |
A |
G |
4: 137,229,605 (GRCm39) |
D73G |
probably benign |
Het |
| Ifitm2 |
A |
G |
7: 140,535,656 (GRCm39) |
V58A |
possibly damaging |
Het |
| Ift172 |
T |
C |
5: 31,414,945 (GRCm39) |
D1359G |
probably benign |
Het |
| Ing1 |
A |
G |
8: 11,607,031 (GRCm39) |
D41G |
probably damaging |
Het |
| Itgal |
C |
T |
7: 126,909,486 (GRCm39) |
T446I |
probably benign |
Het |
| Itgav |
G |
T |
2: 83,633,586 (GRCm39) |
M978I |
probably benign |
Het |
| Jazf1 |
A |
G |
6: 52,754,681 (GRCm39) |
Y132H |
possibly damaging |
Het |
| Lgr4 |
T |
A |
2: 109,829,766 (GRCm39) |
N211K |
probably damaging |
Het |
| Mgat4d |
A |
G |
8: 84,082,350 (GRCm39) |
N100S |
possibly damaging |
Het |
| Mrgprb3 |
T |
C |
7: 48,293,263 (GRCm39) |
Y96C |
probably damaging |
Het |
| Myh11 |
A |
C |
16: 14,023,492 (GRCm39) |
L1562R |
probably damaging |
Het |
| Mylk |
G |
C |
16: 34,699,845 (GRCm39) |
E403Q |
possibly damaging |
Het |
| Myo15a |
A |
G |
11: 60,397,139 (GRCm39) |
Y2667C |
probably damaging |
Het |
| Or14j7 |
T |
A |
17: 38,235,229 (GRCm39) |
C257* |
probably null |
Het |
| Or52ae7 |
A |
G |
7: 103,119,907 (GRCm39) |
I220M |
possibly damaging |
Het |
| Or6c70 |
G |
A |
10: 129,710,407 (GRCm39) |
T73I |
possibly damaging |
Het |
| Or8k37 |
T |
A |
2: 86,469,573 (GRCm39) |
T160S |
possibly damaging |
Het |
| Or8k38 |
C |
T |
2: 86,488,235 (GRCm39) |
C189Y |
possibly damaging |
Het |
| Or9m2 |
T |
A |
2: 87,820,816 (GRCm39) |
Y120* |
probably null |
Het |
| Paox |
G |
T |
7: 139,711,591 (GRCm39) |
G148W |
probably damaging |
Het |
| Pkd1 |
T |
C |
17: 24,799,112 (GRCm39) |
V2777A |
probably benign |
Het |
| Plod2 |
T |
A |
9: 92,477,388 (GRCm39) |
V360E |
probably damaging |
Het |
| Prune2 |
T |
C |
19: 16,998,030 (GRCm39) |
|
probably benign |
Het |
| Sbds |
G |
T |
5: 130,282,919 (GRCm39) |
A3D |
possibly damaging |
Het |
| Sec23a |
T |
C |
12: 59,031,953 (GRCm39) |
T426A |
probably benign |
Het |
| Sec31a |
T |
C |
5: 100,551,929 (GRCm39) |
Y148C |
probably damaging |
Het |
| Shprh |
T |
A |
10: 11,059,631 (GRCm39) |
|
probably benign |
Het |
| Slc16a7 |
A |
G |
10: 125,066,742 (GRCm39) |
V299A |
probably benign |
Het |
| Smg8 |
T |
C |
11: 86,974,439 (GRCm39) |
Y174C |
possibly damaging |
Het |
| Snx22 |
T |
A |
9: 65,976,059 (GRCm39) |
Y58F |
probably damaging |
Het |
| Snx25 |
A |
G |
8: 46,556,667 (GRCm39) |
Y308H |
probably benign |
Het |
| St3gal2 |
A |
G |
8: 111,696,738 (GRCm39) |
|
probably null |
Het |
| Stab1 |
C |
T |
14: 30,861,507 (GRCm39) |
R2500H |
possibly damaging |
Het |
| Steap4 |
T |
C |
5: 8,025,870 (GRCm39) |
S144P |
probably damaging |
Het |
| Stfa3 |
T |
A |
16: 36,272,619 (GRCm39) |
|
probably benign |
Het |
| Tmprss9 |
C |
A |
10: 80,735,157 (GRCm39) |
Q1095K |
probably benign |
Het |
| Top2a |
A |
G |
11: 98,890,052 (GRCm39) |
V1217A |
possibly damaging |
Het |
| Trhr2 |
A |
G |
8: 123,085,228 (GRCm39) |
|
probably null |
Het |
| Trim7 |
A |
G |
11: 48,736,336 (GRCm39) |
E23G |
probably damaging |
Het |
| Trpv3 |
A |
T |
11: 73,188,013 (GRCm39) |
E788V |
probably damaging |
Het |
| Ttn |
A |
G |
2: 76,575,863 (GRCm39) |
I25010T |
probably damaging |
Het |
| Ube2ql1 |
T |
C |
13: 69,887,419 (GRCm39) |
H14R |
unknown |
Het |
| Uggt1 |
C |
T |
1: 36,235,052 (GRCm39) |
R419H |
probably benign |
Het |
| Xpo4 |
A |
G |
14: 57,850,731 (GRCm39) |
V391A |
probably benign |
Het |
| Zfhx3 |
A |
G |
8: 109,520,819 (GRCm39) |
D647G |
probably damaging |
Het |
| Zfp354c |
A |
T |
11: 50,706,457 (GRCm39) |
M206K |
probably benign |
Het |
| Zfp804a |
A |
G |
2: 82,089,264 (GRCm39) |
N1031S |
possibly damaging |
Het |
| Zfp868 |
A |
G |
8: 70,064,882 (GRCm39) |
V151A |
probably benign |
Het |
|
| Other mutations in Aass |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00916:Aass
|
APN |
6 |
23,075,851 (GRCm39) |
missense |
probably benign |
0.10 |
|
IGL01465:Aass
|
APN |
6 |
23,114,838 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL01617:Aass
|
APN |
6 |
23,115,149 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
IGL01810:Aass
|
APN |
6 |
23,107,633 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02024:Aass
|
APN |
6 |
23,113,705 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02167:Aass
|
APN |
6 |
23,122,721 (GRCm39) |
intron |
probably benign |
|
|
IGL02339:Aass
|
APN |
6 |
23,093,965 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02720:Aass
|
APN |
6 |
23,122,702 (GRCm39) |
intron |
probably benign |
|
|
IGL02877:Aass
|
APN |
6 |
23,078,875 (GRCm39) |
nonsense |
probably null |
|
|
IGL02948:Aass
|
APN |
6 |
23,094,318 (GRCm39) |
splice site |
probably benign |
|
|
PIT4651001:Aass
|
UTSW |
6 |
23,118,750 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0152:Aass
|
UTSW |
6 |
23,074,688 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0196:Aass
|
UTSW |
6 |
23,109,519 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0841:Aass
|
UTSW |
6 |
23,075,810 (GRCm39) |
missense |
probably benign |
|
|
R0848:Aass
|
UTSW |
6 |
23,114,984 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0942:Aass
|
UTSW |
6 |
23,075,151 (GRCm39) |
splice site |
probably benign |
|
|
R1082:Aass
|
UTSW |
6 |
23,093,907 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1159:Aass
|
UTSW |
6 |
23,115,137 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1730:Aass
|
UTSW |
6 |
23,121,018 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1818:Aass
|
UTSW |
6 |
23,075,857 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R1906:Aass
|
UTSW |
6 |
23,072,984 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2004:Aass
|
UTSW |
6 |
23,092,561 (GRCm39) |
nonsense |
probably null |
|
|
R2191:Aass
|
UTSW |
6 |
23,078,865 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R3690:Aass
|
UTSW |
6 |
23,091,328 (GRCm39) |
missense |
probably benign |
0.09 |
|
R3843:Aass
|
UTSW |
6 |
23,092,495 (GRCm39) |
nonsense |
probably null |
|
|
R3879:Aass
|
UTSW |
6 |
23,122,520 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4080:Aass
|
UTSW |
6 |
23,109,497 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R4081:Aass
|
UTSW |
6 |
23,109,497 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R4082:Aass
|
UTSW |
6 |
23,109,497 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R4348:Aass
|
UTSW |
6 |
23,113,738 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4622:Aass
|
UTSW |
6 |
23,092,329 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4701:Aass
|
UTSW |
6 |
23,075,855 (GRCm39) |
nonsense |
probably null |
|
|
R4823:Aass
|
UTSW |
6 |
23,107,690 (GRCm39) |
missense |
probably benign |
|
|
R5108:Aass
|
UTSW |
6 |
23,094,207 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5248:Aass
|
UTSW |
6 |
23,109,437 (GRCm39) |
missense |
probably benign |
0.08 |
|
R5481:Aass
|
UTSW |
6 |
23,113,475 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5776:Aass
|
UTSW |
6 |
23,107,649 (GRCm39) |
missense |
possibly damaging |
0.66 |
|
R5883:Aass
|
UTSW |
6 |
23,072,993 (GRCm39) |
missense |
probably benign |
0.04 |
|
R6356:Aass
|
UTSW |
6 |
23,093,901 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6594:Aass
|
UTSW |
6 |
23,113,432 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6784:Aass
|
UTSW |
6 |
23,093,895 (GRCm39) |
missense |
probably null |
1.00 |
|
R6855:Aass
|
UTSW |
6 |
23,114,844 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7184:Aass
|
UTSW |
6 |
23,094,219 (GRCm39) |
missense |
possibly damaging |
0.55 |
|
R7208:Aass
|
UTSW |
6 |
23,074,629 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7464:Aass
|
UTSW |
6 |
23,077,152 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R7750:Aass
|
UTSW |
6 |
23,075,199 (GRCm39) |
missense |
possibly damaging |
0.58 |
|
R7821:Aass
|
UTSW |
6 |
23,120,929 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8262:Aass
|
UTSW |
6 |
23,107,709 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R8303:Aass
|
UTSW |
6 |
23,092,367 (GRCm39) |
missense |
probably benign |
0.03 |
|
R8430:Aass
|
UTSW |
6 |
23,078,981 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8817:Aass
|
UTSW |
6 |
23,097,195 (GRCm39) |
nonsense |
probably null |
|
|
R8941:Aass
|
UTSW |
6 |
23,075,261 (GRCm39) |
splice site |
probably benign |
|
|
R9065:Aass
|
UTSW |
6 |
23,075,746 (GRCm39) |
missense |
probably benign |
0.38 |
|
R9067:Aass
|
UTSW |
6 |
23,077,123 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9068:Aass
|
UTSW |
6 |
23,075,828 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9119:Aass
|
UTSW |
6 |
23,094,000 (GRCm39) |
missense |
probably benign |
0.05 |
|
R9210:Aass
|
UTSW |
6 |
23,075,767 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9212:Aass
|
UTSW |
6 |
23,075,767 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9372:Aass
|
UTSW |
6 |
23,078,856 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9517:Aass
|
UTSW |
6 |
23,113,528 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9626:Aass
|
UTSW |
6 |
23,127,502 (GRCm39) |
missense |
unknown |
|
|
R9704:Aass
|
UTSW |
6 |
23,120,887 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
Z1176:Aass
|
UTSW |
6 |
23,078,856 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- GGCATGACTTCCCCATTGTTCAGG -3'
(R):5'- GGGCAGGGGCTGTAAAATTCATTTG -3'
Sequencing Primer
(F):5'- CCCATTGTTCAGGGAATGATCC -3'
(R):5'- AGGGGCTGTAAAATTCATTTGTCTTC -3'
|
| Protein Function and Prediction |
In lysine metabolism, the first two steps of the lysine-degradation pathway are catalyzed by lysine-ketoglutarate reducase (LKR) and saccharopine dehydrogenase (SDH), respectively. AASS is a bifunctional protein that contains both LKR and SDH activity (1). AASS was detected in all human tissues examined by Northern blot analysis; highest expression was observed in the liver (1).
|
| Background |
Mutations in AASS are linked to hyperlysinemia (OMIM: #238700) and saccaropinuria (OMIM: %268700). Patients with hyperlysinemia are often mentally retarded and exhibit convulsions, have impaired sexual development, lax ligaments and muscles, and mild anemia (2). Patients with saccharopinuria exhibit moderate retardation and EEG abnormalities (3).
|
| References |
1. Sacksteder, K. A., Biery, B. J., Morrell, J. C., Goodman, B. K., Geisbrecht, B. V., Cox, R. P., Gould, S. J., and Geraghty, M. T. (2000) Identification of the Alpha-Aminoadipic Semialdehyde Synthase Gene, which is Defective in Familial Hyperlysinemia. Am J Hum Genet. 66, 1736-1743. |
| Posted On |
2013-06-11 |
| Science Writer |
Anne Murray |
Incidental Mutation