Incidental Mutation 'R0055:Ucp1'
ID |
16008 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Ucp1
|
Ensembl Gene |
ENSMUSG00000031710 |
Gene Name |
uncoupling protein 1 (mitochondrial, proton carrier) |
Synonyms |
Slc25a7 |
MMRRC Submission |
038349-MU
|
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
R0055 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
8 |
Chromosomal Location |
84016981-84025081 bp(+) (GRCm39) |
Type of Mutation |
nonsense |
DNA Base Change (assembly) |
G to T
at 84017233 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Glutamic Acid to Stop codon
at position 8
(E8*)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000034146
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034146]
|
AlphaFold |
P12242 |
Predicted Effect |
probably null
Transcript: ENSMUST00000034146
AA Change: E8*
|
SMART Domains |
Protein: ENSMUSP00000034146 Gene: ENSMUSG00000031710 AA Change: E8*
Domain | Start | End | E-Value | Type |
Pfam:Mito_carr
|
10 |
107 |
5.7e-20 |
PFAM |
Pfam:Mito_carr
|
109 |
206 |
3.3e-20 |
PFAM |
Pfam:Mito_carr
|
209 |
300 |
1.6e-18 |
PFAM |
|
Meta Mutation Damage Score |
0.9755 |
Coding Region Coverage |
- 1x: 89.7%
- 3x: 87.2%
- 10x: 80.9%
- 20x: 71.2%
|
Validation Efficiency |
85% (52/61) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Mitochondrial uncoupling proteins (UCP) are members of the family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. This gene is expressed only in brown adipose tissue, a specialized tissue which functions to produce heat. [provided by RefSeq, Jul 2008] PHENOTYPE: Homozygous null mutants exhibit impaired thermoregulation on some genetic backgrounds. Biochemical alterations in brown fat mitochondria are also observed. [provided by MGI curators]
|
Allele List at MGI |
All alleles(3) : Targeted(2) Spontaneous(1)
|
Other mutations in this stock |
Total: 37 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
A2ml1 |
T |
C |
6: 128,547,057 (GRCm39) |
|
probably benign |
Het |
Atp6v1h |
A |
T |
1: 5,154,677 (GRCm39) |
T2S |
probably benign |
Het |
BC034090 |
A |
T |
1: 155,117,404 (GRCm39) |
L238Q |
probably damaging |
Het |
Ccdc61 |
T |
C |
7: 18,626,461 (GRCm39) |
D128G |
probably damaging |
Het |
Cfap96 |
A |
T |
8: 46,421,198 (GRCm39) |
S108R |
probably damaging |
Het |
Dennd5a |
A |
G |
7: 109,498,998 (GRCm39) |
I955T |
possibly damaging |
Het |
Ephx4 |
T |
C |
5: 107,560,944 (GRCm39) |
L32S |
probably damaging |
Het |
Fbxo21 |
T |
A |
5: 118,138,555 (GRCm39) |
D493E |
probably benign |
Het |
Frmd4b |
A |
T |
6: 97,300,610 (GRCm39) |
|
probably benign |
Het |
Fzd1 |
A |
T |
5: 4,806,037 (GRCm39) |
M515K |
possibly damaging |
Het |
Gli2 |
A |
G |
1: 118,818,138 (GRCm39) |
|
probably benign |
Het |
Gm12887 |
T |
A |
4: 121,473,666 (GRCm39) |
K61N |
probably damaging |
Het |
Grin2a |
A |
T |
16: 9,487,671 (GRCm39) |
V409D |
probably damaging |
Het |
Grin2b |
T |
C |
6: 135,900,201 (GRCm39) |
I227V |
probably benign |
Het |
Helz2 |
T |
G |
2: 180,870,614 (GRCm39) |
D2879A |
possibly damaging |
Het |
Itpr2 |
T |
C |
6: 146,224,631 (GRCm39) |
N1453S |
probably benign |
Het |
Lin7c |
T |
A |
2: 109,726,798 (GRCm39) |
|
probably benign |
Het |
Ly75 |
T |
C |
2: 60,152,262 (GRCm39) |
E1097G |
probably benign |
Het |
Mcm10 |
T |
C |
2: 4,996,218 (GRCm39) |
N882D |
probably damaging |
Het |
Mybph |
G |
T |
1: 134,121,590 (GRCm39) |
V88L |
probably damaging |
Het |
Nefm |
T |
A |
14: 68,358,648 (GRCm39) |
|
probably benign |
Het |
Nf1 |
A |
G |
11: 79,362,377 (GRCm39) |
E1497G |
probably damaging |
Het |
Or2j3 |
T |
C |
17: 38,615,702 (GRCm39) |
S217G |
possibly damaging |
Het |
Or51ah3 |
A |
G |
7: 103,210,244 (GRCm39) |
K187E |
probably damaging |
Het |
Or52e18 |
T |
A |
7: 104,609,703 (GRCm39) |
T79S |
possibly damaging |
Het |
Phf8-ps |
A |
T |
17: 33,285,696 (GRCm39) |
W369R |
probably damaging |
Het |
Plcd3 |
C |
G |
11: 102,968,411 (GRCm39) |
W382S |
probably damaging |
Het |
Plxna1 |
T |
A |
6: 89,306,721 (GRCm39) |
I1370F |
possibly damaging |
Het |
Qng1 |
T |
C |
13: 58,531,980 (GRCm39) |
D192G |
probably damaging |
Het |
Rarb |
G |
A |
14: 16,509,066 (GRCm38) |
R106C |
probably damaging |
Het |
Rps6ka5 |
G |
A |
12: 100,644,839 (GRCm39) |
T37I |
probably damaging |
Het |
Scube1 |
A |
G |
15: 83,518,937 (GRCm39) |
V301A |
probably damaging |
Het |
Slc25a45 |
T |
C |
19: 5,930,495 (GRCm39) |
F3L |
probably damaging |
Het |
Slfn10-ps |
A |
G |
11: 82,921,126 (GRCm39) |
|
noncoding transcript |
Het |
Slit2 |
C |
A |
5: 48,439,068 (GRCm39) |
C1077* |
probably null |
Het |
Zdhhc11 |
C |
T |
13: 74,130,805 (GRCm39) |
Q295* |
probably null |
Het |
Zfp457 |
T |
A |
13: 67,442,098 (GRCm39) |
H63L |
probably damaging |
Het |
|
Other mutations in Ucp1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
PIT4585001:Ucp1
|
UTSW |
8 |
84,020,577 (GRCm39) |
missense |
probably damaging |
1.00 |
R0050:Ucp1
|
UTSW |
8 |
84,020,857 (GRCm39) |
missense |
probably damaging |
1.00 |
R0055:Ucp1
|
UTSW |
8 |
84,017,233 (GRCm39) |
nonsense |
probably null |
|
R0505:Ucp1
|
UTSW |
8 |
84,021,936 (GRCm39) |
missense |
possibly damaging |
0.78 |
R0590:Ucp1
|
UTSW |
8 |
84,018,232 (GRCm39) |
splice site |
probably benign |
|
R0681:Ucp1
|
UTSW |
8 |
84,021,936 (GRCm39) |
missense |
possibly damaging |
0.78 |
R0731:Ucp1
|
UTSW |
8 |
84,024,476 (GRCm39) |
splice site |
probably benign |
|
R1606:Ucp1
|
UTSW |
8 |
84,021,933 (GRCm39) |
missense |
probably damaging |
1.00 |
R1722:Ucp1
|
UTSW |
8 |
84,017,317 (GRCm39) |
missense |
probably benign |
0.25 |
R1809:Ucp1
|
UTSW |
8 |
84,024,496 (GRCm39) |
missense |
probably damaging |
0.99 |
R1823:Ucp1
|
UTSW |
8 |
84,020,661 (GRCm39) |
missense |
probably damaging |
1.00 |
R3809:Ucp1
|
UTSW |
8 |
84,017,270 (GRCm39) |
missense |
probably damaging |
0.99 |
R4085:Ucp1
|
UTSW |
8 |
84,020,580 (GRCm39) |
missense |
probably benign |
0.43 |
R4673:Ucp1
|
UTSW |
8 |
84,021,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R4998:Ucp1
|
UTSW |
8 |
84,024,484 (GRCm39) |
critical splice acceptor site |
probably null |
|
R5163:Ucp1
|
UTSW |
8 |
84,020,832 (GRCm39) |
missense |
possibly damaging |
0.95 |
R5421:Ucp1
|
UTSW |
8 |
84,017,320 (GRCm39) |
missense |
probably benign |
0.12 |
R5790:Ucp1
|
UTSW |
8 |
84,024,520 (GRCm39) |
missense |
possibly damaging |
0.54 |
R5994:Ucp1
|
UTSW |
8 |
84,020,567 (GRCm39) |
missense |
possibly damaging |
0.92 |
R6574:Ucp1
|
UTSW |
8 |
84,020,718 (GRCm39) |
critical splice donor site |
probably null |
|
R6732:Ucp1
|
UTSW |
8 |
84,018,106 (GRCm39) |
missense |
probably benign |
0.08 |
R7282:Ucp1
|
UTSW |
8 |
84,020,531 (GRCm39) |
missense |
probably benign |
0.03 |
R7343:Ucp1
|
UTSW |
8 |
84,021,881 (GRCm39) |
missense |
probably damaging |
0.99 |
R7878:Ucp1
|
UTSW |
8 |
84,024,521 (GRCm39) |
missense |
probably benign |
0.19 |
R8008:Ucp1
|
UTSW |
8 |
84,020,640 (GRCm39) |
missense |
probably benign |
0.32 |
R8365:Ucp1
|
UTSW |
8 |
84,020,628 (GRCm39) |
missense |
probably damaging |
0.97 |
R8899:Ucp1
|
UTSW |
8 |
84,017,216 (GRCm39) |
missense |
probably benign |
0.35 |
R9186:Ucp1
|
UTSW |
8 |
84,017,272 (GRCm39) |
nonsense |
probably null |
|
R9499:Ucp1
|
UTSW |
8 |
84,024,509 (GRCm39) |
missense |
probably damaging |
1.00 |
R9551:Ucp1
|
UTSW |
8 |
84,024,509 (GRCm39) |
missense |
probably damaging |
1.00 |
R9552:Ucp1
|
UTSW |
8 |
84,024,509 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Protein Function and Prediction |
Ucp1 encodes UCP1 (alternatively, thermogenin), a transmembrane member of the mitochondrial anion carrier family (1). UCP1 is involved in regulating β-adrenergically controlled nonshivering thermogenesis in brown adipocytes (1). UCP1 facilitates maximum mitochondrial respiration by promoting proton reentry into the mitochondrial matrix to subsequently produce heat (1-4). The UCP1-catalyzed proton leak in the inner mitochondrial membrane can be inhibited by purine nucleotides and activated by free fatty acids (1). In addition, norephinephrine is the main positive regulator of UCP synthesis and activity (4).
|
Expression/Localization |
Ucp1 expression is limited to mature brown adipocytes (2) and is inserted into the inner mitochondrial membrane (1).
|
Background |
Mutations in UCP1 are controversially linked to susceptibility to obesity [OMIM: # 601665; (5)].
Ucp1tm1Kz/tm1Kz; MGI:1857471
(129S1.Cg-Ucptm1Kz x B6.Cg-Ucptm1Kz)F1
Mitochondria from homozygotes exhibit an impaired response to free fatty acid-induced decoupling to a de-energized state, but they maintained normal body temperature upon exposure to cold (3).
Ucp1tm1Kz/tm1Kz; MGI:1857471
129S1.Cg-Ucptm1Kz
In this genetic background, homozyoges have increased brown adipose tissue weight and mitochondria exhibit an impaired response to free fatty acid-induced decoupling to a de-energized state (3). Homozygotes lose body core temperature rapidly upon exposure to cold temperatures (3).
Ucp1tm1Kz/tm1Kz; MGI:1857471
B6.Cg-Ucptm1Kz
In this genetic background, homozyoges have increased brown adipose tissue weight, reduced weight of white adipose tissue, and mitochondria exhibit an impaired response to free fatty acid-induced decoupling to a de-energized state (3;6). These mice also have a decreased susceptibility to diet-induce obesity, decreased body weight, and impaired adaptive thermogenesis (3;6).
Ucp1tm1Kz/tm1Kz; MGI:1857471
involves: 129S2/SvPas
Homozygotes in this genetic background have increased mass of brown fat, decreased susceptibility to diet-induced obesity, impaired adaptive thermogenesis, and abnormal oxygen consumption (7;8)
Ucp1tm1Kz/tm1Kz; MGI:1857471
involves: 129S2/SvPas * C57BL/6J
Homozygotes in this genetic background have mitochondria that respond to free fatty acids by uncoupling to a de-energized state similar to controls. In addition, mutant mitochondria are in a perpetually energized state (9).
|
References |
1. Klingenspor, M., Fromme, T., Hughes, D. A.,Jr, Manzke, L., Polymeropoulos, E., Riemann, T., Trzcionka, M., Hirschberg, V., and Jastroch, M. (2008) An Ancient Look at UCP1. Biochim Biophys Acta. 1777, 637-641.
3. Hofmann, W. E., Liu, X., Bearden, C. M., Harper, M. E., and Kozak, L. P. (2001) Effects of Genetic Background on Thermoregulation and Fatty Acid-Induced Uncoupling of Mitochondria in UCP1-Deficient Mice. J Biol Chem. 276, 12460-12465.
5. Jia, J. J., Tian, Y. B., Cao, Z. H., Tao, L. L., Zhang, X., Gao, S. Z., Ge, C. R., Lin, Q. Y., and Jois, M. (2010) The Polymorphisms of UCP1 Genes Associated with Fat Metabolism, Obesity and Diabetes. Mol Biol Rep. 37, 1513-1522.
6. Liu, X., Rossmeisl, M., McClaine, J., Riachi, M., Harper, M. E., and Kozak, L. P. (2003) Paradoxical Resistance to Diet-Induced Obesity in UCP1-Deficient Mice. J Clin Invest. 111, 399-407.
7. Enerback, S., Jacobsson, A., Simpson, E. M., Guerra, C., Yamashita, H., Harper, M. E., and Kozak, L. P. (1997) Mice Lacking Mitochondrial Uncoupling Protein are Cold-Sensitive but Not Obese. Nature. 387, 90-94.
8. Gong, D. W., Monemdjou, S., Gavrilova, O., Leon, L. R., Marcus-Samuels, B., Chou, C. J., Everett, C., Kozak, L. P., Li, C., Deng, C., Harper, M. E., and Reitman, M. L. (2000) Lack of Obesity and Normal Response to Fasting and Thyroid Hormone in Mice Lacking Uncoupling Protein-3. J Biol Chem. 275, 16251-16257.
|
Posted On |
2013-01-08 |
Science Writer |
Anne Murray |