Mutagenetix > Incidental Mutation

Incidental Mutation 'P0038:Atmin'

7731

Institutional Source

Beutler Lab

Gene Symbol

Atmin

Ensembl Gene

ENSMUSG00000047388

Gene Name

ATM interactor

Synonyms

gpg6, Asciz

MMRRC Submission

038287-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

P0038 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

117670132-117687184 bp(+) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 117683775 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Stop codon at position 478 (C478*)

Ref Sequence

ENSEMBL: ENSMUSP00000104727 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000109099]

AlphaFold

Q6P9S1

Predicted Effect

probably null
Transcript: ENSMUST00000109099
AA Change: C478*

SMART Domains

Protein: ENSMUSP00000104727
Gene: ENSMUSG00000047388
AA Change: C478*

Domain	Start	End	E-Value	Type
low complexity region	2	34	N/A	INTRINSIC
low complexity region	46	62	N/A	INTRINSIC
ZnF_C2H2	80	105	2.49e-1	SMART
ZnF_C2H2	127	156	7.11e0	SMART
ZnF_C2H2	161	181	4.5e1	SMART
ZnF_C2H2	187	210	1.06e2	SMART
low complexity region	289	304	N/A	INTRINSIC
low complexity region	644	657	N/A	INTRINSIC
low complexity region	722	738	N/A	INTRINSIC

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 79.6%
3x: 69.7%
10x: 40.2%
20x: 18.1%

Validation Efficiency

86% (80/93)

MGI Phenotype

PHENOTYPE: Mice homozygous for a knock-out allele exhibit fetal lethality, craniofacial defects, midbrain exencephaly, and premature senescence of mouse embryonic fibroblasts. Homozygotes for an ENU-induced mutation exhibit left-right patterning defects. [provided by MGI curators]

Allele List at MGI

All alleles(4) : Targeted(3) Gene trapped(1)

Other mutations in this stock

Total: 16 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Atad2b	C	A	12: 5,004,536 (GRCm39)		probably benign	Het
Cdh13	G	A	8: 119,401,843 (GRCm39)	V82M	probably damaging	Het
Dip2c	A	C	13: 9,697,018 (GRCm39)	T1310P	probably damaging	Het
Eral1	A	T	11: 77,966,847 (GRCm39)	D189E	probably damaging	Het
Fstl5	A	G	3: 76,052,369 (GRCm39)	Y33C	probably damaging	Het
Gjb4	A	T	4: 127,245,293 (GRCm39)	V216D	probably benign	Het
Lars2	T	C	9: 123,206,842 (GRCm39)	V103A	probably damaging	Het
Mfsd12	C	T	10: 81,198,052 (GRCm39)	T311I	probably benign	Het
Mtrex	A	C	13: 113,047,513 (GRCm39)	Y277*	probably null	Het
Paf1	T	C	7: 28,096,350 (GRCm39)		probably null	Het
Rfc1	T	C	5: 65,445,304 (GRCm39)	T435A	probably damaging	Het
Siglec1	T	C	2: 130,923,359 (GRCm39)	N462S	probably benign	Het
Tnks1bp1	C	T	2: 84,892,755 (GRCm39)	T232I	probably benign	Het
Trpc6	A	T	9: 8,649,512 (GRCm39)	N574I	possibly damaging	Het
Ttll7	T	C	3: 146,650,939 (GRCm39)	F700L	possibly damaging	Het
Zc3hav1	G	A	6: 38,309,469 (GRCm39)	T451M	probably damaging	Het

Other mutations in Atmin

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00639:Atmin	APN	8	117,683,396 (GRCm39)	missense	probably damaging	1.00
IGL02680:Atmin	APN	8	117,684,236 (GRCm39)	missense	probably damaging	1.00
IGL03355:Atmin	APN	8	117,684,164 (GRCm39)	nonsense	probably null
K3955:Atmin	UTSW	8	117,683,775 (GRCm39)	nonsense	probably null
R1440:Atmin	UTSW	8	117,684,115 (GRCm39)	missense	probably damaging	0.98
R1498:Atmin	UTSW	8	117,681,540 (GRCm39)	missense	probably benign	0.21
R1515:Atmin	UTSW	8	117,681,579 (GRCm39)	missense	possibly damaging	0.87
R2094:Atmin	UTSW	8	117,684,277 (GRCm39)	missense	probably damaging	1.00
R2306:Atmin	UTSW	8	117,684,389 (GRCm39)	missense	probably benign	0.04
R2363:Atmin	UTSW	8	117,681,653 (GRCm39)	critical splice donor site	probably null
R2866:Atmin	UTSW	8	117,683,112 (GRCm39)	missense	probably benign
R3743:Atmin	UTSW	8	117,683,312 (GRCm39)	missense	probably benign	0.02
R3901:Atmin	UTSW	8	117,683,036 (GRCm39)	missense	probably benign	0.00
R3902:Atmin	UTSW	8	117,683,036 (GRCm39)	missense	probably benign	0.00
R4664:Atmin	UTSW	8	117,684,698 (GRCm39)	missense	probably damaging	1.00
R4665:Atmin	UTSW	8	117,684,698 (GRCm39)	missense	probably damaging	1.00
R4666:Atmin	UTSW	8	117,684,698 (GRCm39)	missense	probably damaging	1.00
R5441:Atmin	UTSW	8	117,684,696 (GRCm39)	missense	probably damaging	0.99
R5496:Atmin	UTSW	8	117,683,911 (GRCm39)	missense	probably benign	0.01
R6914:Atmin	UTSW	8	117,683,452 (GRCm39)	missense	probably benign	0.02
R6942:Atmin	UTSW	8	117,683,452 (GRCm39)	missense	probably benign	0.02
R6965:Atmin	UTSW	8	117,683,777 (GRCm39)	missense	probably damaging	1.00
R7172:Atmin	UTSW	8	117,683,281 (GRCm39)	missense	probably damaging	1.00
R7492:Atmin	UTSW	8	117,683,657 (GRCm39)	missense	probably damaging	1.00
R7647:Atmin	UTSW	8	117,684,661 (GRCm39)	missense	possibly damaging	0.86
R8068:Atmin	UTSW	8	117,683,389 (GRCm39)	missense	probably benign	0.00
R8726:Atmin	UTSW	8	117,681,525 (GRCm39)	missense	possibly damaging	0.63
R8734:Atmin	UTSW	8	117,681,525 (GRCm39)	missense	possibly damaging	0.63
R8991:Atmin	UTSW	8	117,679,665 (GRCm39)	missense	probably damaging	1.00
R9284:Atmin	UTSW	8	117,684,019 (GRCm39)	missense	probably benign	0.32
R9429:Atmin	UTSW	8	117,670,307 (GRCm39)	missense	probably benign	0.02
R9478:Atmin	UTSW	8	117,681,537 (GRCm39)	missense	probably damaging	0.99
R9535:Atmin	UTSW	8	117,683,327 (GRCm39)	missense	probably damaging	0.96
R9720:Atmin	UTSW	8	117,681,653 (GRCm39)	critical splice donor site	probably null
V7732:Atmin	UTSW	8	117,683,218 (GRCm39)	missense	probably damaging	1.00
X0020:Atmin	UTSW	8	117,679,721 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

Atmin (alternatively, Asciz) is a DNA damage response protein [(1); reviewed in (2)]. In chicken DT40 B lymphocytes, Atmin was shown to antagonize base damage-induced recombinatorial immunonoglobulin gene diversification (3). In mice lacking Atmin in B cells, ATM signaling is impaired and the mice develop B cell lymphomas. These mice have defective peripheral V(D)J rearrangement and CSR, resulting in Igh and IgI translocations. Taken together, this study showed that Atmin is necessary for genomic stability and tumor suppression in B cells (4). Recently, researchers found that Atmin is involved in a feedback loop with the dynein light chain, Dynll1 (LC8) (5).

Expression/Localization

Atmin is ubiquitously expressed, with highest expression in the placenta, lung, and kidney (6).

Background

Atmin^{tm1.1Axbe/tm1.1Axbe}; MGI:4868762

involves: BALB/c * C57BL/6

Homozygotes are embryonic lethal around E16.5 and mouse embryonic fibroblasts exhibit increased DNA damage when cultured in high oxygen compared with wild-type mice as well as exencephaly and abnormal craniofacial morphology (7)

Atmin^{tm1.1Jhh/tm1.1Jhh}; MGI:4881337

C57BL/6-Atmin^tm1.1Jhh

Homozygotes are embryonic lethal between E16.5 and E18.5 (8). At E11.5 and E12.5, mice lack developing pulmonary epithelium unlike wild-type mice (8). The mice have decreased fetal weight, growth retardation, exencephaly, abnormal heart position, and thymus hypoplasia (8). Mouse embryonic fibroblasts from the homozygotes exhibit abnormal base-excision repair, increased cellular sensitivity to methylmethanesulfonate, increased cellular sensitivity to hydrogen peroxide, and early cellular replicative senescence (8).

References

1. McNees, C. J., Conlan, L. A., Tenis, N., and Heierhorst, J. (2005) ASCIZ Regulates Lesion-Specific Rad51 Focus Formation and Apoptosis After Methylating DNA Damage. EMBO J. 24, 2447-2457.

2. Heierhorst, J. (2008) Mdt1/ASCIZ: A New DNA Damage Response Protein Family. Cell Cycle. 7, 2654-2660.

3. Oka, H., Sakai, W., Sonoda, E., Nakamura, J., Asagoshi, K., Wilson, S. H., Kobayashi, M., Yamamoto, K., Heierhorst, J., Takeda, S., and Taniguchi, Y. (2008) DNA Damage Response Protein ASCIZ Links Base Excision Repair with Immunoglobulin Gene Conversion. Biochem Biophys Res Commun. 371, 225-229.

4. Loizou, J. I., Sancho, R., Kanu, N., Bolland, D. J., Yang, F., Rada, C., Corcoran, A. E., and Behrens, A. (2011) ATMIN is Required for Maintenance of Genomic Stability and Suppression of B Cell Lymphoma. Cancer Cell. 19, 587-600.

5. Jurado, S., Conlan, L. A., Baker, E. K., Ng, J. L., Tenis, N., Hoch, N. C., Gleeson, K., Smeets, M., Izon, D., and Heierhorst, J. (2012) ATM Substrate Chk2-Interacting Zn2+ Finger (ASCIZ) is a Bi-Functional Transcriptional Activator and Feedback Sensor in the Regulation of Dynein Light Chain (DYNLL1) Expression. J Biol Chem. 287, 3156-3164.

6. Ishikawa, K., Nagase, T., Nakajima, D., Seki, N., Ohira, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1997) Prediction of the Coding Sequences of Unidentified Human Genes. VIII. 78 New cDNA Clones from Brain which Code for Large Proteins in Vitro. DNA Res. 4, 307-313.

7. Kanu, N., Penicud, K., Hristova, M., Wong, B., Irvine, E., Plattner, F., Raivich, G., and Behrens, A. (2010) The ATM Cofactor ATMIN Protects Against Oxidative Stress and Accumulation of DNA Damage in the Aging Brain. J Biol Chem. 285, 38534-38542.

8. Jurado, S., Smyth, I., van Denderen, B., Tenis, N., Hammet, A., Hewitt, K., Ng, J. L., McNees, C. J., Kozlov, S. V., Oka, H., Kobayashi, M., Conlan, L. A., Cole, T. J., Yamamoto, K., Taniguchi, Y., Takeda, S., Lavin, M. F., and Heierhorst, J. (2010) Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis. PLoS Genet. 6, e1001170.

Posted On

2012-10-29

Science Writer

Anne Murray