Incidental Mutation 'R0060:Flad1'
| ID |
17210 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Flad1
|
| Ensembl Gene |
ENSMUSG00000042642 |
| Gene Name |
flavin adenine dinucleotide synthetase 1 |
| Synonyms |
Pp591, A930017E24Rik |
| MMRRC Submission |
038353-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.889)
|
| Stock # |
R0060 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
3 |
| Chromosomal Location |
89309980-89319188 bp(-) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
G to A
at 89309552 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Stop codon
at position 515
(R515*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000051366
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000050398]
[ENSMUST00000057431]
[ENSMUST00000107426]
[ENSMUST00000129308]
|
| AlphaFold |
Q8R123 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000050398
AA Change: R515*
|
| SMART Domains |
Protein: ENSMUSP00000051366
Gene: ENSMUSG00000042642
AA Change: R515*
| Domain | Start | End | E-Value | Type |
|---|
|
MoCF_biosynth
|
19 |
180 |
7.52e-24 |
SMART |
|
Pfam:PAPS_reduct
|
303 |
460 |
5.2e-25 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000057431
|
| SMART Domains |
Protein: ENSMUSP00000052968
Gene: ENSMUSG00000078173
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:LEP503
|
1 |
61 |
6.1e-39 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000107426
|
| SMART Domains |
Protein: ENSMUSP00000103049
Gene: ENSMUSG00000042642
| Domain | Start | End | E-Value | Type |
|---|
|
MoCF_biosynth
|
19 |
180 |
7.52e-24 |
SMART |
|
Pfam:PAPS_reduct
|
303 |
460 |
4.7e-25 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000126926
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000129308
|
| SMART Domains |
Protein: ENSMUSP00000122252
Gene: ENSMUSG00000042642
| Domain | Start | End | E-Value | Type |
|---|
|
MoCF_biosynth
|
19 |
180 |
7.52e-24 |
SMART |
|
Pfam:PAPS_reduct
|
303 |
460 |
4.7e-25 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000145400
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000152143
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153969
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 90.4%
- 3x: 88.3%
- 10x: 83.8%
- 20x: 78.1%
|
| Validation Efficiency |
94% (74/79) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the enzyme that catalyzes adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
|
| Allele List at MGI |
All alleles(19) : Targeted(3) Gene trapped(16)
|
| Other mutations in this stock |
Total: 52 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1810065E05Rik |
A |
C |
11: 58,313,008 (GRCm39) |
|
probably benign |
Het |
| 4930432E11Rik |
A |
G |
7: 29,273,595 (GRCm39) |
|
noncoding transcript |
Het |
| A630091E08Rik |
A |
G |
7: 98,192,875 (GRCm39) |
|
noncoding transcript |
Het |
| Abca8a |
T |
C |
11: 109,961,306 (GRCm39) |
T539A |
probably damaging |
Het |
| Adam34 |
A |
T |
8: 44,128,920 (GRCm39) |
|
probably benign |
Het |
| Ankrd60 |
A |
T |
2: 173,414,406 (GRCm39) |
M1K |
probably null |
Het |
| Cald1 |
T |
C |
6: 34,692,394 (GRCm39) |
|
probably benign |
Het |
| Capn7 |
T |
C |
14: 31,087,561 (GRCm39) |
|
probably benign |
Het |
| Cd109 |
G |
A |
9: 78,610,389 (GRCm39) |
E1145K |
probably damaging |
Het |
| Celsr1 |
A |
T |
15: 85,806,399 (GRCm39) |
V2353D |
probably damaging |
Het |
| Cep135 |
A |
T |
5: 76,769,197 (GRCm39) |
I616F |
probably benign |
Het |
| Cep162 |
T |
A |
9: 87,119,878 (GRCm39) |
|
probably benign |
Het |
| Cep350 |
C |
T |
1: 155,804,372 (GRCm39) |
D904N |
probably damaging |
Het |
| Cep85 |
T |
C |
4: 133,894,611 (GRCm39) |
D65G |
probably damaging |
Het |
| Cfdp1 |
T |
C |
8: 112,566,986 (GRCm39) |
|
probably benign |
Het |
| Chl1 |
T |
A |
6: 103,688,019 (GRCm39) |
|
probably benign |
Het |
| Colec10 |
G |
A |
15: 54,302,542 (GRCm39) |
|
probably benign |
Het |
| Crxos |
A |
G |
7: 15,632,448 (GRCm39) |
T40A |
possibly damaging |
Het |
| Dnhd1 |
A |
G |
7: 105,317,721 (GRCm39) |
D472G |
probably damaging |
Het |
| Dpp6 |
C |
A |
5: 27,803,817 (GRCm39) |
N254K |
probably damaging |
Het |
| Eps8l3 |
T |
C |
3: 107,786,857 (GRCm39) |
L11S |
probably damaging |
Het |
| Fzd5 |
T |
C |
1: 64,774,835 (GRCm39) |
T309A |
probably benign |
Het |
| Gm19685 |
T |
C |
17: 61,075,418 (GRCm39) |
|
|
Het |
| Gsdme |
A |
G |
6: 50,198,009 (GRCm39) |
I317T |
possibly damaging |
Het |
| H2bc1 |
A |
T |
13: 24,117,928 (GRCm39) |
I71N |
possibly damaging |
Het |
| Incenp |
A |
G |
19: 9,862,823 (GRCm39) |
|
probably benign |
Het |
| Itgad |
T |
C |
7: 127,802,158 (GRCm39) |
S979P |
probably damaging |
Het |
| Kat2b |
T |
C |
17: 53,961,571 (GRCm39) |
V557A |
probably damaging |
Het |
| Lamc1 |
A |
T |
1: 153,117,614 (GRCm39) |
|
probably benign |
Het |
| Lgi4 |
G |
A |
7: 30,762,996 (GRCm39) |
G157D |
probably damaging |
Het |
| Mga |
T |
C |
2: 119,791,442 (GRCm39) |
|
probably null |
Het |
| Nubpl |
T |
C |
12: 52,357,470 (GRCm39) |
|
probably benign |
Het |
| Or2b4 |
T |
C |
17: 38,116,891 (GRCm39) |
L285P |
probably damaging |
Het |
| Or5be3 |
T |
C |
2: 86,864,118 (GRCm39) |
Y149C |
probably damaging |
Het |
| Or8c20 |
C |
T |
9: 38,260,808 (GRCm39) |
S143F |
probably benign |
Het |
| Peak1 |
A |
T |
9: 56,135,107 (GRCm39) |
I78K |
probably damaging |
Het |
| Prune2 |
T |
A |
19: 16,981,097 (GRCm39) |
F85I |
probably damaging |
Het |
| Rbm11 |
G |
T |
16: 75,395,667 (GRCm39) |
D113Y |
probably damaging |
Het |
| Rif1 |
C |
T |
2: 52,001,129 (GRCm39) |
R1528C |
probably damaging |
Het |
| Sema4d |
A |
G |
13: 51,859,293 (GRCm39) |
|
probably benign |
Het |
| Slc30a4 |
T |
A |
2: 122,527,104 (GRCm39) |
T381S |
probably benign |
Het |
| Slf2 |
G |
T |
19: 44,936,443 (GRCm39) |
G696V |
probably damaging |
Het |
| Suv39h2 |
T |
C |
2: 3,465,953 (GRCm39) |
Y134C |
probably damaging |
Het |
| Tmem273 |
C |
A |
14: 32,528,726 (GRCm39) |
|
probably benign |
Het |
| Tmem89 |
T |
A |
9: 108,744,485 (GRCm39) |
V126D |
probably damaging |
Het |
| Trf |
T |
C |
9: 103,098,121 (GRCm39) |
T46A |
probably benign |
Het |
| Trmt6 |
C |
T |
2: 132,648,689 (GRCm39) |
R415Q |
possibly damaging |
Het |
| Trp53bp1 |
T |
C |
2: 121,035,006 (GRCm39) |
K1625E |
probably damaging |
Het |
| Usp6nl |
T |
A |
2: 6,445,701 (GRCm39) |
D559E |
probably benign |
Het |
| Wdr75 |
A |
G |
1: 45,855,777 (GRCm39) |
D476G |
probably benign |
Het |
| Wrap53 |
A |
C |
11: 69,454,256 (GRCm39) |
L261V |
possibly damaging |
Het |
| Zcchc4 |
T |
A |
5: 52,964,420 (GRCm39) |
I292N |
possibly damaging |
Het |
|
| Other mutations in Flad1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00422:Flad1
|
APN |
3 |
89,313,160 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02065:Flad1
|
APN |
3 |
89,316,294 (GRCm39) |
missense |
probably damaging |
1.00 |
|
brick
|
UTSW |
3 |
89,318,494 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Impaler
|
UTSW |
3 |
89,310,758 (GRCm39) |
missense |
probably damaging |
0.99 |
|
stone
|
UTSW |
3 |
89,316,109 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3821:Flad1
|
UTSW |
3 |
89,318,494 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3822:Flad1
|
UTSW |
3 |
89,318,494 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4458:Flad1
|
UTSW |
3 |
89,316,241 (GRCm39) |
missense |
probably benign |
0.14 |
|
R4838:Flad1
|
UTSW |
3 |
89,313,217 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5296:Flad1
|
UTSW |
3 |
89,318,503 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6522:Flad1
|
UTSW |
3 |
89,310,490 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6703:Flad1
|
UTSW |
3 |
89,315,897 (GRCm39) |
missense |
probably benign |
|
|
R7000:Flad1
|
UTSW |
3 |
89,309,549 (GRCm39) |
utr 3 prime |
probably benign |
|
|
R7114:Flad1
|
UTSW |
3 |
89,314,837 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7127:Flad1
|
UTSW |
3 |
89,310,725 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7365:Flad1
|
UTSW |
3 |
89,315,972 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R7626:Flad1
|
UTSW |
3 |
89,310,718 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7662:Flad1
|
UTSW |
3 |
89,310,758 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8097:Flad1
|
UTSW |
3 |
89,316,442 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8296:Flad1
|
UTSW |
3 |
89,316,109 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8332:Flad1
|
UTSW |
3 |
89,314,828 (GRCm39) |
missense |
probably benign |
|
|
R8531:Flad1
|
UTSW |
3 |
89,310,517 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8711:Flad1
|
UTSW |
3 |
89,316,415 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9090:Flad1
|
UTSW |
3 |
89,315,858 (GRCm39) |
nonsense |
probably null |
|
|
R9271:Flad1
|
UTSW |
3 |
89,315,858 (GRCm39) |
nonsense |
probably null |
|
|
R9767:Flad1
|
UTSW |
3 |
89,310,718 (GRCm39) |
missense |
probably benign |
0.01 |
|
| Protein Function and Prediction |
Flad1 encodes FAD synthetase (FADS), an enzyme that catalyzes the adenylation of riboflavin into the redox cofactor FAD (1). Within the cells, dietary riboflavin (i.e., vitamin B2) is converted into catalytically active cofactors via riboflavin kinase, which converts riboflavin into flavin mononucleotide (FMN) and FADS (1). Silencing of the Flad1 homologue in C. elegans resulted in decreased ATP, an increase in ROS, and impaired locomotion proposed to be due to altered cholinergic transmission (2). The human FLAD1 gene has two isoforms and both possess FADS activity (1). The two isoforms differ in at the N-terminus (3).
|
| Expression/Localization |
Most FADS is isolated from the liver, but in depth expression analysis has not been conducted. Isoform 1 of FLAD1 is localized in the mitochondria (3).
|
| References |
1. Brizio, C., Galluccio, M., Wait, R., Torchetti, E. M., Bafunno, V., Accardi, R., Gianazza, E., Indiveri, C., and Barile, M. (2006) Over-Expression in Escherichia Coli and Characterization of Two Recombinant Isoforms of Human FAD Synthetase. Biochem Biophys Res Commun. 344, 1008-1016.
2. Liuzzi, V. C., Giancaspero, T. A., Gianazza, E., Banfi, C., Barile, M., and De Giorgi, C. (2012) Silencing of FAD Synthase Gene in Caenorhabditis Elegans Upsets Protein Homeostasis and Impacts on Complex Behavioral Patterns. Biochim Biophys Acta. 1820, 521-531.
3. Torchetti, E. M., Brizio, C., Colella, M., Galluccio, M., Giancaspero, T. A., Indiveri, C., Roberti, M., and Barile, M. (2010) Mitochondrial Localization of Human FAD Synthetase Isoform 1. Mitochondrion. 10, 263-273. |
| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation