Incidental Mutation 'R0007:Cdh8'
ID |
8080 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Cdh8
|
Ensembl Gene |
ENSMUSG00000036510 |
Gene Name |
cadherin 8 |
Synonyms |
cad8 |
MMRRC Submission |
038302-MU
|
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
R0007 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
8 |
Chromosomal Location |
99751103-100143103 bp(-) (GRCm39) |
Type of Mutation |
nonsense |
DNA Base Change (assembly) |
A to T
at 99957088 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Leucine to Stop codon
at position 205
(L205*)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000123619
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000093249]
[ENSMUST00000128860]
[ENSMUST00000142129]
[ENSMUST00000142475]
[ENSMUST00000145601]
[ENSMUST00000155527]
|
AlphaFold |
P97291 |
Predicted Effect |
probably null
Transcript: ENSMUST00000093249
AA Change: L205*
|
SMART Domains |
Protein: ENSMUSP00000090935 Gene: ENSMUSG00000036510 AA Change: L205*
Domain | Start | End | E-Value | Type |
low complexity region
|
12 |
24 |
N/A |
INTRINSIC |
CA
|
84 |
165 |
9.52e-17 |
SMART |
CA
|
189 |
274 |
7.14e-30 |
SMART |
CA
|
298 |
390 |
8.16e-16 |
SMART |
CA
|
413 |
494 |
6.14e-20 |
SMART |
CA
|
517 |
604 |
1.16e-11 |
SMART |
transmembrane domain
|
622 |
644 |
N/A |
INTRINSIC |
Pfam:Cadherin_C
|
645 |
712 |
1.4e-16 |
PFAM |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000126895
|
Predicted Effect |
probably null
Transcript: ENSMUST00000128860
AA Change: L205*
|
SMART Domains |
Protein: ENSMUSP00000117326 Gene: ENSMUSG00000036510 AA Change: L205*
Domain | Start | End | E-Value | Type |
low complexity region
|
12 |
24 |
N/A |
INTRINSIC |
CA
|
84 |
165 |
9.52e-17 |
SMART |
CA
|
189 |
274 |
7.14e-30 |
SMART |
CA
|
298 |
390 |
8.16e-16 |
SMART |
CA
|
413 |
494 |
6.14e-20 |
SMART |
CA
|
517 |
604 |
1.16e-11 |
SMART |
transmembrane domain
|
622 |
644 |
N/A |
INTRINSIC |
Pfam:Cadherin_C
|
647 |
792 |
7e-54 |
PFAM |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000142129
AA Change: L205*
|
SMART Domains |
Protein: ENSMUSP00000114507 Gene: ENSMUSG00000036510 AA Change: L205*
Domain | Start | End | E-Value | Type |
low complexity region
|
12 |
24 |
N/A |
INTRINSIC |
CA
|
84 |
165 |
9.52e-17 |
SMART |
CA
|
189 |
274 |
7.14e-30 |
SMART |
CA
|
298 |
390 |
8.16e-16 |
SMART |
CA
|
413 |
494 |
6.14e-20 |
SMART |
CA
|
517 |
604 |
1.16e-11 |
SMART |
transmembrane domain
|
622 |
644 |
N/A |
INTRINSIC |
Pfam:Cadherin_C
|
645 |
702 |
5.3e-17 |
PFAM |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000142475
AA Change: L205*
|
SMART Domains |
Protein: ENSMUSP00000115977 Gene: ENSMUSG00000036510 AA Change: L205*
Domain | Start | End | E-Value | Type |
low complexity region
|
12 |
24 |
N/A |
INTRINSIC |
CA
|
84 |
165 |
9.52e-17 |
SMART |
Pfam:Cadherin
|
172 |
242 |
2.2e-10 |
PFAM |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000145601
AA Change: L205*
|
SMART Domains |
Protein: ENSMUSP00000122493 Gene: ENSMUSG00000036510 AA Change: L205*
Domain | Start | End | E-Value | Type |
low complexity region
|
12 |
24 |
N/A |
INTRINSIC |
CA
|
84 |
165 |
9.52e-17 |
SMART |
CA
|
189 |
274 |
7.14e-30 |
SMART |
CA
|
298 |
390 |
8.16e-16 |
SMART |
CA
|
413 |
502 |
1.27e-3 |
SMART |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000155527
AA Change: L205*
|
SMART Domains |
Protein: ENSMUSP00000123619 Gene: ENSMUSG00000036510 AA Change: L205*
Domain | Start | End | E-Value | Type |
low complexity region
|
12 |
24 |
N/A |
INTRINSIC |
CA
|
84 |
165 |
9.52e-17 |
SMART |
CA
|
189 |
274 |
7.14e-30 |
SMART |
CA
|
298 |
390 |
8.16e-16 |
SMART |
CA
|
413 |
494 |
6.14e-20 |
SMART |
CA
|
517 |
604 |
1.16e-11 |
SMART |
transmembrane domain
|
622 |
644 |
N/A |
INTRINSIC |
Pfam:Cadherin_C
|
645 |
745 |
1.8e-19 |
PFAM |
|
Meta Mutation Damage Score |
0.9754 |
Coding Region Coverage |
- 1x: 75.9%
- 3x: 62.7%
- 10x: 33.8%
- 20x: 16.7%
|
Validation Efficiency |
95% (54/57) |
MGI Phenotype |
FUNCTION: This gene encodes a member of the cadherin family of calcium-dependent glycoproteins that mediate cell adhesion and regulate many morphogenetic events during development. The encoded preproprotein is further processed to generate a mature protein. Mice lacking the encoded protein exhibit reduced behavioral responses to cold, but not thermal stimuli. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. Multiple distinct genes of the cadherin family, including this gene, are found on chromosome 8. [provided by RefSeq, Oct 2015] PHENOTYPE: Mice homozygous for a null allele are viable, fertile and overtly normal but display abnormal CNS synaptic transmission, raise their tails in response to stress, and show reduced sensitivity to cutaneous cold stimuli. [provided by MGI curators]
|
Allele List at MGI |
All alleles(4) : Targeted(4)
|
Other mutations in this stock |
Total: 23 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
4931406B18Rik |
T |
C |
7: 43,147,466 (GRCm39) |
|
probably benign |
Het |
Cntnap2 |
A |
C |
6: 45,969,007 (GRCm39) |
N250H |
possibly damaging |
Het |
Col7a1 |
T |
C |
9: 108,790,471 (GRCm39) |
V973A |
unknown |
Het |
Denr |
T |
A |
5: 124,062,877 (GRCm39) |
Y127N |
probably damaging |
Het |
Diaph3 |
C |
A |
14: 87,104,056 (GRCm39) |
R776L |
possibly damaging |
Het |
F2 |
T |
C |
2: 91,460,952 (GRCm39) |
E260G |
probably benign |
Het |
Il1rl1 |
C |
T |
1: 40,485,331 (GRCm39) |
T261I |
possibly damaging |
Het |
Lama3 |
T |
A |
18: 12,630,938 (GRCm39) |
|
probably benign |
Het |
Map2k5 |
A |
T |
9: 63,201,006 (GRCm39) |
I209N |
probably damaging |
Het |
Myo1b |
T |
A |
1: 51,815,413 (GRCm39) |
R650S |
probably damaging |
Het |
Nek10 |
T |
A |
14: 14,840,574 (GRCm38) |
H153Q |
probably benign |
Het |
Nlrp9a |
T |
C |
7: 26,250,515 (GRCm39) |
|
probably benign |
Het |
Pcnx4 |
T |
A |
12: 72,602,353 (GRCm39) |
F281I |
possibly damaging |
Het |
Pcsk5 |
C |
A |
19: 17,632,225 (GRCm39) |
G314C |
probably damaging |
Het |
Pkhd1l1 |
T |
C |
15: 44,437,794 (GRCm39) |
|
probably benign |
Het |
Polr2b |
T |
C |
5: 77,488,284 (GRCm39) |
V828A |
probably benign |
Het |
Slc44a4 |
G |
A |
17: 35,140,230 (GRCm39) |
A60T |
probably damaging |
Het |
Sparcl1 |
T |
A |
5: 104,234,946 (GRCm39) |
Q523L |
probably damaging |
Het |
Tnfrsf21 |
C |
T |
17: 43,349,104 (GRCm39) |
H239Y |
probably benign |
Het |
Trhr |
T |
C |
15: 44,092,547 (GRCm39) |
|
probably benign |
Het |
Trim16 |
A |
G |
11: 62,719,944 (GRCm39) |
M84V |
probably benign |
Het |
Trpm3 |
G |
A |
19: 22,964,893 (GRCm39) |
A1453T |
probably benign |
Het |
Zfp990 |
C |
A |
4: 145,264,008 (GRCm39) |
H335Q |
probably benign |
Het |
|
Other mutations in Cdh8 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00402:Cdh8
|
APN |
8 |
100,006,322 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL01377:Cdh8
|
APN |
8 |
99,760,021 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL01845:Cdh8
|
APN |
8 |
99,825,586 (GRCm39) |
splice site |
probably benign |
|
IGL02166:Cdh8
|
APN |
8 |
99,917,083 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02392:Cdh8
|
APN |
8 |
99,757,387 (GRCm39) |
missense |
probably damaging |
0.96 |
R0179:Cdh8
|
UTSW |
8 |
99,838,344 (GRCm39) |
missense |
possibly damaging |
0.84 |
R0196:Cdh8
|
UTSW |
8 |
99,917,066 (GRCm39) |
missense |
probably damaging |
0.99 |
R0220:Cdh8
|
UTSW |
8 |
99,838,311 (GRCm39) |
missense |
probably benign |
0.21 |
R0271:Cdh8
|
UTSW |
8 |
99,838,347 (GRCm39) |
missense |
possibly damaging |
0.83 |
R0592:Cdh8
|
UTSW |
8 |
100,006,110 (GRCm39) |
missense |
probably damaging |
1.00 |
R0612:Cdh8
|
UTSW |
8 |
100,127,546 (GRCm39) |
missense |
probably benign |
0.02 |
R1404:Cdh8
|
UTSW |
8 |
100,006,250 (GRCm39) |
missense |
probably damaging |
1.00 |
R1404:Cdh8
|
UTSW |
8 |
100,006,250 (GRCm39) |
missense |
probably damaging |
1.00 |
R1588:Cdh8
|
UTSW |
8 |
99,917,039 (GRCm39) |
missense |
probably damaging |
1.00 |
R1635:Cdh8
|
UTSW |
8 |
99,757,656 (GRCm39) |
missense |
probably damaging |
1.00 |
R1717:Cdh8
|
UTSW |
8 |
99,757,337 (GRCm39) |
missense |
probably damaging |
1.00 |
R1781:Cdh8
|
UTSW |
8 |
100,006,290 (GRCm39) |
missense |
probably damaging |
0.98 |
R1781:Cdh8
|
UTSW |
8 |
99,917,094 (GRCm39) |
splice site |
probably null |
|
R1862:Cdh8
|
UTSW |
8 |
99,917,026 (GRCm39) |
missense |
probably damaging |
1.00 |
R1895:Cdh8
|
UTSW |
8 |
100,006,189 (GRCm39) |
missense |
possibly damaging |
0.84 |
R1912:Cdh8
|
UTSW |
8 |
99,825,502 (GRCm39) |
missense |
probably damaging |
1.00 |
R2005:Cdh8
|
UTSW |
8 |
99,760,103 (GRCm39) |
splice site |
probably null |
|
R2142:Cdh8
|
UTSW |
8 |
99,838,325 (GRCm39) |
missense |
probably damaging |
1.00 |
R2197:Cdh8
|
UTSW |
8 |
99,922,897 (GRCm39) |
missense |
probably damaging |
1.00 |
R2512:Cdh8
|
UTSW |
8 |
100,127,495 (GRCm39) |
missense |
probably benign |
0.05 |
R3085:Cdh8
|
UTSW |
8 |
99,923,018 (GRCm39) |
missense |
probably benign |
0.00 |
R3436:Cdh8
|
UTSW |
8 |
100,127,350 (GRCm39) |
splice site |
probably benign |
|
R3898:Cdh8
|
UTSW |
8 |
99,898,005 (GRCm39) |
missense |
probably damaging |
0.98 |
R4470:Cdh8
|
UTSW |
8 |
100,143,321 (GRCm39) |
unclassified |
probably benign |
|
R4615:Cdh8
|
UTSW |
8 |
100,006,254 (GRCm39) |
missense |
probably damaging |
1.00 |
R4652:Cdh8
|
UTSW |
8 |
99,751,491 (GRCm39) |
missense |
probably benign |
|
R4666:Cdh8
|
UTSW |
8 |
99,751,534 (GRCm39) |
missense |
possibly damaging |
0.71 |
R4798:Cdh8
|
UTSW |
8 |
99,751,558 (GRCm39) |
nonsense |
probably null |
|
R4871:Cdh8
|
UTSW |
8 |
99,757,536 (GRCm39) |
missense |
probably damaging |
1.00 |
R5170:Cdh8
|
UTSW |
8 |
100,006,182 (GRCm39) |
missense |
probably damaging |
1.00 |
R5406:Cdh8
|
UTSW |
8 |
99,923,002 (GRCm39) |
missense |
probably damaging |
1.00 |
R5564:Cdh8
|
UTSW |
8 |
99,757,498 (GRCm39) |
missense |
possibly damaging |
0.57 |
R5686:Cdh8
|
UTSW |
8 |
99,759,854 (GRCm39) |
missense |
probably benign |
0.00 |
R6311:Cdh8
|
UTSW |
8 |
100,127,527 (GRCm39) |
missense |
probably damaging |
0.99 |
R6786:Cdh8
|
UTSW |
8 |
99,950,579 (GRCm39) |
missense |
probably benign |
0.19 |
R6855:Cdh8
|
UTSW |
8 |
99,916,849 (GRCm39) |
missense |
probably damaging |
0.99 |
R6950:Cdh8
|
UTSW |
8 |
99,757,395 (GRCm39) |
missense |
probably benign |
0.18 |
R7112:Cdh8
|
UTSW |
8 |
99,922,984 (GRCm39) |
missense |
probably damaging |
1.00 |
R7181:Cdh8
|
UTSW |
8 |
99,825,557 (GRCm39) |
missense |
probably benign |
|
R7384:Cdh8
|
UTSW |
8 |
99,957,138 (GRCm39) |
missense |
probably benign |
|
R7400:Cdh8
|
UTSW |
8 |
100,006,192 (GRCm39) |
missense |
probably damaging |
1.00 |
R7537:Cdh8
|
UTSW |
8 |
99,825,517 (GRCm39) |
nonsense |
probably null |
|
R7763:Cdh8
|
UTSW |
8 |
100,006,306 (GRCm39) |
nonsense |
probably null |
|
R8130:Cdh8
|
UTSW |
8 |
99,757,676 (GRCm39) |
missense |
probably damaging |
0.98 |
R8215:Cdh8
|
UTSW |
8 |
99,757,498 (GRCm39) |
missense |
possibly damaging |
0.57 |
R8314:Cdh8
|
UTSW |
8 |
99,898,011 (GRCm39) |
missense |
probably damaging |
1.00 |
R8443:Cdh8
|
UTSW |
8 |
99,757,672 (GRCm39) |
missense |
possibly damaging |
0.56 |
R9673:Cdh8
|
UTSW |
8 |
99,757,367 (GRCm39) |
missense |
possibly damaging |
0.71 |
R9756:Cdh8
|
UTSW |
8 |
99,759,976 (GRCm39) |
missense |
probably damaging |
1.00 |
X0022:Cdh8
|
UTSW |
8 |
100,006,107 (GRCm39) |
missense |
probably damaging |
1.00 |
Z1088:Cdh8
|
UTSW |
8 |
100,006,134 (GRCm39) |
missense |
probably damaging |
1.00 |
Z1176:Cdh8
|
UTSW |
8 |
99,916,837 (GRCm39) |
missense |
probably null |
0.89 |
Z1176:Cdh8
|
UTSW |
8 |
99,897,955 (GRCm39) |
missense |
probably benign |
0.02 |
|
Protein Function and Prediction |
Cadherin 8 (Cdh8) is an integral membrane protein that mediates calcium-dependent cell-cell adhesion. CDH8 has been implicated in both kidney morphogenesis as well as tumorigenesis in some types of renal cell carcinoma (1). A knockout model demonstrated that Cdh8 is necessary to establish physiological coupling between cold-sensitive sensory neurons and their target dorsal horn neurons (2). Furthermore, Cdh8 regulates mossy fiber fasciculation and targeting (3).
|
Expression/Localization |
Northern blot analysis detected Cdh8 expression only in rat brain, with multiple transcripts present (4;5). Cdh8 can be detected in the kidney during early stages of kidney development (1).
|
Background |
Cdh8tm1Mta/tm1Mta; MGI:3707077
B6.129P2-Cdh8tm1Mta
Mice homozygous for a null allele are viable, fertile and overtly normal but display abnormal CNS synaptic transmission, raise their tails in response to stress, and show reduced sensitivity to cutaneous cold stimuli (2).
|
References |
1. Blaschke, S., Mueller, C. A., Markovic-Lipkovski, J., Puch, S., Miosge, N., Becker, V., Mueller, G. A., and Klein, G. (2002) Expression of Cadherin-8 in Renal Cell Carcinoma and Fetal Kidney. Int J Cancer. 101, 327-334.
2. Suzuki, S. C., Furue, H., Koga, K., Jiang, N., Nohmi, M., Shimazaki, Y., Katoh-Fukui, Y., Yokoyama, M., Yoshimura, M., and Takeichi, M. (2007) Cadherin-8 is Required for the First Relay Synapses to Receive Functional Inputs from Primary Sensory Afferents for Cold Sensation. J Neurosci. 27, 3466-3476.
3. Bekirov, I. H., Nagy, V., Svoronos, A., Huntley, G. W., and Benson, D. L. (2008) Cadherin-8 and N-Cadherin Differentially Regulate Pre- and Postsynaptic Development of the Hippocampal Mossy Fiber Pathway. Hippocampus. 18, 349-363.
5. Kido, M., Obata, S., Tanihara, H., Rochelle, J. M., Seldin, M. F., Taketani, S., and Suzuki, S. T. (1998) Molecular Properties and Chromosomal Location of Cadherin-8. Genomics. 48, 186-194.
|
Posted On |
2012-11-20 |
Science Writer |
Anne Murray |