Mutagenetix > Incidental Mutation

Incidental Mutation 'R0007:Cdh8'

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) question?

Stock #

R0007 (G1)

Quality Score

Status

Validated

Chromosome

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

Cdh8^{tm1Mta/tm1Mta}; MGI:3707077

B6.129P2-Cdh8^tm1Mta

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.

4. Suzuki, S., Sano, K., and Tanihara, H. (1991) Diversity of the Cadherin Family: Evidence for Eight New Cadherins in Nervous Tissue. Cell Regul. 2, 261-270.

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