Incidental Mutation 'R0046:Actl7a'
ID |
16123 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Actl7a
|
Ensembl Gene |
ENSMUSG00000070979 |
Gene Name |
actin-like 7a |
Synonyms |
Tact2, t-actin 2 |
MMRRC Submission |
038340-MU
|
Accession Numbers |
|
Essential gene? |
Possibly essential
(E-score: 0.552)
|
Stock # |
R0046 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
4 |
Chromosomal Location |
56743422-56744925 bp(+) (GRCm39) |
Type of Mutation |
nonsense |
DNA Base Change (assembly) |
A to T
at 56743877 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Lysine to Stop codon
at position 135
(K135*)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000092692
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000095079]
[ENSMUST00000095080]
[ENSMUST00000181745]
|
AlphaFold |
Q9QY84 |
Predicted Effect |
probably null
Transcript: ENSMUST00000095079
AA Change: K135*
|
SMART Domains |
Protein: ENSMUSP00000092692 Gene: ENSMUSG00000070979 AA Change: K135*
Domain | Start | End | E-Value | Type |
Pfam:ACTL7A_N
|
6 |
70 |
1.3e-39 |
PFAM |
ACTIN
|
74 |
440 |
4.63e-123 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000095080
|
SMART Domains |
Protein: ENSMUSP00000092693 Gene: ENSMUSG00000070980
Domain | Start | End | E-Value | Type |
ACTIN
|
51 |
418 |
1.6e-117 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000181745
|
Meta Mutation Damage Score |
0.9705 |
Coding Region Coverage |
- 1x: 89.2%
- 3x: 86.2%
- 10x: 78.3%
- 20x: 64.0%
|
Validation Efficiency |
98% (86/88) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene (ACTL7A), and related gene, ACTL7B, are intronless, and are located approximately 4 kb apart in a head-to-head orientation within the familial dysautonomia candidate region on 9q31. Based on mutational analysis of the ACTL7A gene in patients with this disorder, it was concluded that it is unlikely to be involved in the pathogenesis of dysautonomia. The ACTL7A gene is expressed in a wide variety of adult tissues, however, its exact function is not known. [provided by RefSeq, Jul 2008]
|
Allele List at MGI |
|
Other mutations in this stock |
Total: 57 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Adamts16 |
A |
G |
13: 70,911,579 (GRCm39) |
S871P |
probably benign |
Het |
Adcy10 |
A |
T |
1: 165,367,403 (GRCm39) |
I558F |
probably damaging |
Het |
Adsl |
T |
G |
15: 80,846,989 (GRCm39) |
|
probably null |
Het |
Aldob |
T |
C |
4: 49,543,842 (GRCm39) |
I47V |
possibly damaging |
Het |
Alkbh8 |
A |
G |
9: 3,343,247 (GRCm39) |
E46G |
probably damaging |
Het |
Atp1a4 |
A |
T |
1: 172,067,664 (GRCm39) |
L533Q |
probably benign |
Het |
Auts2 |
T |
C |
5: 131,799,624 (GRCm39) |
|
noncoding transcript |
Het |
B3gnt3 |
T |
C |
8: 72,145,567 (GRCm39) |
Y267C |
probably damaging |
Het |
Ccdc39 |
A |
G |
3: 33,898,301 (GRCm39) |
F15L |
possibly damaging |
Het |
Cntnap5c |
T |
G |
17: 58,666,295 (GRCm39) |
D1108E |
probably benign |
Het |
Col14a1 |
G |
A |
15: 55,272,359 (GRCm39) |
|
probably benign |
Het |
Col9a3 |
G |
A |
2: 180,251,280 (GRCm39) |
A317T |
possibly damaging |
Het |
Cpt1c |
A |
T |
7: 44,609,256 (GRCm39) |
|
probably benign |
Het |
Cpt2 |
A |
G |
4: 107,761,559 (GRCm39) |
|
probably null |
Het |
Crebrf |
T |
A |
17: 26,982,308 (GRCm39) |
L565M |
probably damaging |
Het |
Dmxl1 |
T |
A |
18: 50,011,149 (GRCm39) |
V1102E |
probably benign |
Het |
Dock4 |
G |
A |
12: 40,787,359 (GRCm39) |
|
probably benign |
Het |
Dpp3 |
G |
T |
19: 4,964,671 (GRCm39) |
N545K |
probably damaging |
Het |
Elmo2 |
T |
A |
2: 165,140,646 (GRCm39) |
N275I |
probably damaging |
Het |
Farp1 |
A |
G |
14: 121,492,925 (GRCm39) |
K509R |
probably benign |
Het |
Flg |
T |
A |
3: 93,185,028 (GRCm39) |
|
probably benign |
Het |
Gas2l2 |
A |
T |
11: 83,312,736 (GRCm39) |
W859R |
probably damaging |
Het |
Gatm |
T |
C |
2: 122,431,225 (GRCm39) |
D254G |
probably damaging |
Het |
Gjd4 |
T |
A |
18: 9,280,998 (GRCm39) |
I27F |
probably damaging |
Het |
Gm19410 |
A |
G |
8: 36,269,799 (GRCm39) |
E1148G |
probably benign |
Het |
Haus5 |
C |
T |
7: 30,353,605 (GRCm39) |
V591I |
probably benign |
Het |
Kcnab3 |
G |
A |
11: 69,221,053 (GRCm39) |
|
probably null |
Het |
Limk1 |
T |
C |
5: 134,701,615 (GRCm39) |
Y96C |
probably damaging |
Het |
Lrp2bp |
T |
A |
8: 46,466,192 (GRCm39) |
Y100* |
probably null |
Het |
Ly75 |
A |
T |
2: 60,169,801 (GRCm39) |
|
probably benign |
Het |
Mamstr |
T |
G |
7: 45,291,194 (GRCm39) |
|
probably benign |
Het |
Man1a |
A |
G |
10: 53,795,283 (GRCm39) |
Y657H |
probably damaging |
Het |
Marf1 |
G |
A |
16: 13,929,591 (GRCm39) |
P1672S |
possibly damaging |
Het |
Mboat7 |
T |
C |
7: 3,686,817 (GRCm39) |
Y341C |
probably damaging |
Het |
Nhsl1 |
A |
T |
10: 18,401,417 (GRCm39) |
N881I |
probably damaging |
Het |
Nox3 |
T |
C |
17: 3,733,236 (GRCm39) |
Y225C |
probably benign |
Het |
Or4c109 |
C |
T |
2: 88,817,693 (GRCm39) |
M284I |
probably benign |
Het |
Or4c35 |
C |
T |
2: 89,808,851 (GRCm39) |
T243I |
probably damaging |
Het |
Pclo |
C |
T |
5: 14,590,493 (GRCm39) |
T931M |
unknown |
Het |
Pfas |
G |
T |
11: 68,881,293 (GRCm39) |
R1025S |
probably benign |
Het |
Prg4 |
T |
C |
1: 150,331,837 (GRCm39) |
T279A |
possibly damaging |
Het |
Psma1 |
A |
T |
7: 113,866,440 (GRCm39) |
|
probably benign |
Het |
Rab11fip1 |
A |
G |
8: 27,643,149 (GRCm39) |
L550P |
probably damaging |
Het |
Rgs12 |
T |
A |
5: 35,122,664 (GRCm39) |
I149N |
probably damaging |
Het |
Rmnd5a |
T |
C |
6: 71,376,215 (GRCm39) |
H195R |
probably damaging |
Het |
Rnf17 |
T |
C |
14: 56,708,830 (GRCm39) |
L750P |
probably damaging |
Het |
Rtcb |
T |
C |
10: 85,793,520 (GRCm39) |
N18D |
probably benign |
Het |
Seh1l |
T |
C |
18: 67,925,086 (GRCm39) |
|
probably null |
Het |
Sptbn2 |
T |
C |
19: 4,795,405 (GRCm39) |
|
probably benign |
Het |
Stag3 |
C |
T |
5: 138,281,285 (GRCm39) |
|
probably benign |
Het |
Taar2 |
G |
A |
10: 23,817,393 (GRCm39) |
R311H |
probably benign |
Het |
Taok3 |
C |
T |
5: 117,410,294 (GRCm39) |
Q829* |
probably null |
Het |
Tsbp1 |
T |
C |
17: 34,679,095 (GRCm39) |
|
probably null |
Het |
Ttn |
A |
G |
2: 76,781,886 (GRCm39) |
|
probably benign |
Het |
Unc79 |
A |
G |
12: 103,091,940 (GRCm39) |
E1756G |
probably damaging |
Het |
Usp35 |
A |
T |
7: 96,962,804 (GRCm39) |
|
probably null |
Het |
Zbtb40 |
A |
G |
4: 136,714,589 (GRCm39) |
C1067R |
probably damaging |
Het |
|
Other mutations in Actl7a |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00792:Actl7a
|
APN |
4 |
56,743,944 (GRCm39) |
missense |
possibly damaging |
0.86 |
IGL01767:Actl7a
|
APN |
4 |
56,743,980 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02626:Actl7a
|
APN |
4 |
56,744,353 (GRCm39) |
missense |
possibly damaging |
0.89 |
R0046:Actl7a
|
UTSW |
4 |
56,743,877 (GRCm39) |
nonsense |
probably null |
|
R1741:Actl7a
|
UTSW |
4 |
56,744,252 (GRCm39) |
missense |
probably benign |
0.03 |
R1920:Actl7a
|
UTSW |
4 |
56,744,135 (GRCm39) |
missense |
probably damaging |
1.00 |
R2984:Actl7a
|
UTSW |
4 |
56,744,531 (GRCm39) |
missense |
probably benign |
0.00 |
R3716:Actl7a
|
UTSW |
4 |
56,744,295 (GRCm39) |
missense |
possibly damaging |
0.67 |
R4779:Actl7a
|
UTSW |
4 |
56,743,632 (GRCm39) |
missense |
probably benign |
0.07 |
R5391:Actl7a
|
UTSW |
4 |
56,743,661 (GRCm39) |
missense |
probably benign |
|
R5540:Actl7a
|
UTSW |
4 |
56,744,388 (GRCm39) |
missense |
probably benign |
0.00 |
R5723:Actl7a
|
UTSW |
4 |
56,744,310 (GRCm39) |
missense |
probably damaging |
0.99 |
R5902:Actl7a
|
UTSW |
4 |
56,743,827 (GRCm39) |
missense |
probably damaging |
1.00 |
R5903:Actl7a
|
UTSW |
4 |
56,743,827 (GRCm39) |
missense |
probably damaging |
1.00 |
R5922:Actl7a
|
UTSW |
4 |
56,743,827 (GRCm39) |
missense |
probably damaging |
1.00 |
R6010:Actl7a
|
UTSW |
4 |
56,743,870 (GRCm39) |
missense |
possibly damaging |
0.50 |
R6786:Actl7a
|
UTSW |
4 |
56,744,116 (GRCm39) |
nonsense |
probably null |
|
R7168:Actl7a
|
UTSW |
4 |
56,743,769 (GRCm39) |
missense |
probably benign |
|
R7568:Actl7a
|
UTSW |
4 |
56,744,498 (GRCm39) |
missense |
probably damaging |
1.00 |
R8230:Actl7a
|
UTSW |
4 |
56,743,768 (GRCm39) |
missense |
probably damaging |
1.00 |
R8305:Actl7a
|
UTSW |
4 |
56,743,744 (GRCm39) |
missense |
probably benign |
0.41 |
|
Protein Function and Prediction |
Actl7a is a member of the actin-related T-actin protein family and functions in spermiogenesis to facilitate the structural morphogenesis of spermatozoa (1;2). Actl7a forms a complex with the cytoskeletal proteins Tes and Mena in spermatids (3) and is an essential component of capacitation in mouse spermatozoa (4). Anti-Aclt7a antibodies reduced the fertilizing potential of mouse spermatozoa in vitro (5). Also, immunization with the Actl7a protein lead to reduced fertility in both female and male mice (5).
|
Expression/Localization |
Actl7a is expressed specifically in the mouse testis including the sperm heads (the acrosome) and tails within the nucleus (1).
|
References |
1. Tanaka, H., Iguchi, N., Egydio de Carvalho, C., Tadokoro, Y., Yomogida, K., and Nishimune, Y. (2003) Novel Actin-Like Proteins T-ACTIN 1 and T-ACTIN 2 are Differentially Expressed in the Cytoplasm and Nucleus of Mouse Haploid Germ Cells. Biol Reprod. 69, 475-482.
2. Chadwick, B. P., Mull, J., Helbling, L. A., Gill, S., Leyne, M., Robbins, C. M., Pinkett, H. W., Makalowska, I., Maayan, C., Blumenfeld, A., Axelrod, F. B., Brownstein, M., Gusella, J. F., and Slaugenhaupt, S. A. (1999) Cloning, Mapping, and Expression of Two Novel Actin Genes, Actin-Like-7A (ACTL7A) and Actin-Like-7B (ACTL7B), from the Familial Dysautonomia Candidate Region on 9q31. Genomics. 58, 302-309.
3. Boeda, B., Knowles, P. P., Briggs, D. C., Murray-Rust, J., Soriano, E., Garvalov, B. K., McDonald, N. Q., and Way, M. (2011) Molecular Recognition of the Tes LIM2-3 Domains by the Actin-Related Protein Arp7A. J Biol Chem. 286, 11543-11554.
4. Fu, J., Song, W., Zong, S., Koide, S. S., Miao, S., and Wang, L. (2012) Dynamic Alterations in the Expression and Localization of ACTL7a during Capacitation in Mouse Spermatozoa. Fertil Steril. .
5. Fu, J., Wang, Y., Fok, K. L., Yang, D., Qiu, Y., Chan, H. C., Koide, S. S., Miao, S., and Wang, L. (2012) Anti-ACTL7a Antibodies: A Cause of Infertility. Fertil Steril. 97, 1226-33.e1-8.
|
Posted On |
2013-01-08 |
Science Writer |
Anne Murray |