Incidental Mutation 'P0026:Fam20a'
| ID |
8016 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Fam20a
|
| Ensembl Gene |
ENSMUSG00000020614 |
| Gene Name |
FAM20A, golgi associated secretory pathway pseudokinase |
| Synonyms |
|
| MMRRC Submission |
038279-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
P0026 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
109563752-109613989 bp(-) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
A to T
at 109566667 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000020938
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000020938]
[ENSMUST00000155559]
|
| AlphaFold |
Q8CID3 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000020938
|
| SMART Domains |
Protein: ENSMUSP00000020938
Gene: ENSMUSG00000020614
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
9 |
28 |
N/A |
INTRINSIC |
|
low complexity region
|
50 |
61 |
N/A |
INTRINSIC |
|
Pfam:Fam20C
|
306 |
522 |
8.9e-101 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000144972
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000146408
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000155559
|
| SMART Domains |
Protein: ENSMUSP00000116687
Gene: ENSMUSG00000020614
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
9 |
28 |
N/A |
INTRINSIC |
|
low complexity region
|
50 |
61 |
N/A |
INTRINSIC |
|
Pfam:DUF1193
|
305 |
525 |
3.2e-103 |
PFAM |
|
| Meta Mutation Damage Score |
0.9495 |
| Coding Region Coverage |
- 1x: 85.6%
- 3x: 78.9%
- 10x: 59.5%
- 20x: 38.1%
|
| Validation Efficiency |
97% (63/65) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This locus encodes a protein that is likely secreted and may function in hematopoiesis. A mutation at this locus has been associated with amelogenesis imperfecta and gingival hyperplasia syndrome. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit abnormal ameloblast morphology, disrupted dental enamel formation in both incisor and molar teeth, abnormal kidney morphology, disseminated calcifications of muscular arteries, and intrapulmonary calcifications. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(2) : Targeted(2)
|
| Other mutations in this stock |
Total: 26 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abi2 |
A |
G |
1: 60,492,882 (GRCm39) |
N182D |
probably benign |
Het |
| Acad10 |
T |
C |
5: 121,775,415 (GRCm39) |
Y429C |
probably damaging |
Het |
| Aifm3 |
A |
T |
16: 17,324,981 (GRCm39) |
|
probably benign |
Het |
| Bud13 |
A |
G |
9: 46,199,656 (GRCm39) |
H339R |
probably benign |
Het |
| Cpa1 |
T |
A |
6: 30,640,905 (GRCm39) |
M132K |
probably damaging |
Het |
| Dapk1 |
T |
A |
13: 60,865,963 (GRCm39) |
|
probably benign |
Het |
| Dchs1 |
A |
T |
7: 105,407,612 (GRCm39) |
N2073K |
probably damaging |
Het |
| Dnah2 |
A |
T |
11: 69,355,773 (GRCm39) |
N2227K |
probably damaging |
Het |
| Dnpep |
C |
T |
1: 75,285,329 (GRCm39) |
V468I |
probably benign |
Het |
| Elf3 |
A |
G |
1: 135,183,711 (GRCm39) |
|
probably null |
Het |
| Fam124a |
T |
G |
14: 62,843,571 (GRCm39) |
L360V |
probably damaging |
Het |
| Fermt3 |
A |
G |
19: 6,991,792 (GRCm39) |
S140P |
probably damaging |
Het |
| Gm10440 |
T |
C |
5: 54,513,511 (GRCm39) |
|
noncoding transcript |
Het |
| Il12rb1 |
A |
G |
8: 71,265,185 (GRCm39) |
D167G |
probably damaging |
Het |
| Ints8 |
T |
A |
4: 11,225,788 (GRCm39) |
K590* |
probably null |
Het |
| Kcnu1 |
T |
C |
8: 26,382,150 (GRCm39) |
F500S |
probably damaging |
Het |
| Mrm3 |
T |
C |
11: 76,138,326 (GRCm39) |
V238A |
probably damaging |
Het |
| Rap1gap2 |
A |
G |
11: 74,458,036 (GRCm39) |
|
probably benign |
Het |
| Rusc2 |
T |
A |
4: 43,415,840 (GRCm39) |
V382E |
possibly damaging |
Het |
| Slc9a5 |
A |
G |
8: 106,081,923 (GRCm39) |
N216S |
probably damaging |
Het |
| Snx7 |
A |
T |
3: 117,633,672 (GRCm39) |
F63I |
probably damaging |
Het |
| Syne2 |
A |
G |
12: 75,926,994 (GRCm39) |
|
probably benign |
Het |
| Tenm4 |
T |
C |
7: 96,523,734 (GRCm39) |
Y1751H |
probably damaging |
Het |
| Trappc9 |
G |
A |
15: 72,824,931 (GRCm39) |
P366S |
probably damaging |
Het |
| Trim17 |
A |
G |
11: 58,862,084 (GRCm39) |
D372G |
possibly damaging |
Het |
| Zfp354a |
G |
A |
11: 50,952,325 (GRCm39) |
G85R |
probably null |
Het |
|
| Other mutations in Fam20a |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00827:Fam20a
|
APN |
11 |
109,568,588 (GRCm39) |
splice site |
probably benign |
|
|
IGL01296:Fam20a
|
APN |
11 |
109,576,177 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
IGL01319:Fam20a
|
APN |
11 |
109,569,284 (GRCm39) |
splice site |
probably benign |
|
|
IGL01322:Fam20a
|
APN |
11 |
109,573,738 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02086:Fam20a
|
APN |
11 |
109,564,239 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02563:Fam20a
|
APN |
11 |
109,568,620 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
IGL02883:Fam20a
|
APN |
11 |
109,565,953 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02893:Fam20a
|
APN |
11 |
109,612,414 (GRCm39) |
missense |
probably benign |
0.00 |
|
Infamy
|
UTSW |
11 |
109,564,168 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
snide
|
UTSW |
11 |
109,612,201 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
ungainly
|
UTSW |
11 |
109,573,696 (GRCm39) |
nonsense |
probably null |
|
|
R0726:Fam20a
|
UTSW |
11 |
109,568,020 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1317:Fam20a
|
UTSW |
11 |
109,568,664 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1462:Fam20a
|
UTSW |
11 |
109,568,143 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1462:Fam20a
|
UTSW |
11 |
109,568,143 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1751:Fam20a
|
UTSW |
11 |
109,568,664 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1761:Fam20a
|
UTSW |
11 |
109,568,664 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1889:Fam20a
|
UTSW |
11 |
109,564,380 (GRCm39) |
missense |
probably benign |
0.30 |
|
R1895:Fam20a
|
UTSW |
11 |
109,564,380 (GRCm39) |
missense |
probably benign |
0.30 |
|
R1971:Fam20a
|
UTSW |
11 |
109,576,237 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2192:Fam20a
|
UTSW |
11 |
109,565,449 (GRCm39) |
missense |
probably benign |
0.13 |
|
R3745:Fam20a
|
UTSW |
11 |
109,568,616 (GRCm39) |
missense |
probably benign |
0.17 |
|
R4684:Fam20a
|
UTSW |
11 |
109,612,513 (GRCm39) |
missense |
unknown |
|
|
R4835:Fam20a
|
UTSW |
11 |
109,564,389 (GRCm39) |
missense |
probably benign |
0.40 |
|
R5045:Fam20a
|
UTSW |
11 |
109,568,711 (GRCm39) |
missense |
probably benign |
0.38 |
|
R5161:Fam20a
|
UTSW |
11 |
109,564,196 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5715:Fam20a
|
UTSW |
11 |
109,569,257 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5817:Fam20a
|
UTSW |
11 |
109,564,244 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R5960:Fam20a
|
UTSW |
11 |
109,566,795 (GRCm39) |
intron |
probably benign |
|
|
R6162:Fam20a
|
UTSW |
11 |
109,573,696 (GRCm39) |
nonsense |
probably null |
|
|
R6312:Fam20a
|
UTSW |
11 |
109,565,456 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7231:Fam20a
|
UTSW |
11 |
109,612,201 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R7311:Fam20a
|
UTSW |
11 |
109,565,454 (GRCm39) |
nonsense |
probably null |
|
|
R7366:Fam20a
|
UTSW |
11 |
109,564,168 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R8013:Fam20a
|
UTSW |
11 |
109,576,332 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R8014:Fam20a
|
UTSW |
11 |
109,576,332 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R9086:Fam20a
|
UTSW |
11 |
109,566,754 (GRCm39) |
nonsense |
probably null |
|
|
R9751:Fam20a
|
UTSW |
11 |
109,565,992 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Protein Function and Prediction |
Fam20a is a member of the FAM20 family of secreted glycoproteins (1). The function of Fam20a is unknown, but it is proposed to play a role in enamel development and gingival homeostasis (2).
|
| Expression/Localization |
Fam20a is differentially expressed during experimentally induced myeloid differentiation in the murine EML hematopoietic stem cell line (1). Fam20a is expressed in ameloblasts and gingivae (2).
|
| Background |
Mutations in FAM20A are linked to Amelogenesis imperfecta and gingival fibromatosis syndrome [OMIM: # 614253; (2-4)], an autosomal recessive condition characterized by mild gingival fibromatosis and dental anomalies, including hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay of tooth eruption, hypodontia/oligodontia, pericoronal radiolucencies, and unerupted teeth (3).
Fam20atm1Lex/tm1Lex; MGI:5432376
involves: 129S5/SvEvBrd * C57BL/6
Severe amelogenesis imperfecta (AI) was present in the homozygous animals. The mice developed disseminated calcifications of muscular arteries and intrapulmonary calcifications (5).
Note: heterozygotes are produced at lower numbers than expected
|
| References |
1. Nalbant, D., Youn, H., Nalbant, S. I., Sharma, S., Cobos, E., Beale, E. G., Du, Y., and Williams, S. C. (2005) FAM20: An Evolutionarily Conserved Family of Secreted Proteins Expressed in Hematopoietic Cells. BMC Genomics. 6, 11.
2. O'Sullivan, J., Bitu, C. C., Daly, S. B., Urquhart, J. E., Barron, M. J., Bhaskar, S. S., Martelli-Junior, H., dos Santos Neto, P. E., Mansilla, M. A., Murray, J. C., Coletta, R. D., Black, G. C., and Dixon, M. J. (2011) Whole-Exome Sequencing Identifies FAM20A Mutations as a Cause of Amelogenesis Imperfecta and Gingival Hyperplasia Syndrome. Am J Hum Genet. 88, 616-620.
3. Martelli-Junior, H., Bonan, P. R., Dos Santos, L. A., Santos, S. M., Cavalcanti, M. G., and Coletta, R. D. (2008) Case Reports of a New Syndrome Associating Gingival Fibromatosis and Dental Abnormalities in a Consanguineous Family. J Periodontol. 79, 1287-1296.
4. Cho, S. H., Seymen, F., Lee, K. E., Lee, S. K., Kweon, Y. S., Kim, K. J., Jung, S. E., Song, S. J., Yildirim, M., Bayram, M., Tuna, E. B., Gencay, K., and Kim, J. W. (2012) Novel FAM20A Mutations in Hypoplastic Amelogenesis Imperfecta. Hum Mutat. 33, 91-94.
5. Vogel, P., Hansen, G. M., Read, R. W., Vance, R. B., Thiel, M., Liu, J., Wrongski, T. J., Smith, D. D., Jeter-Jones, S., and Brommage, R. (2012) Amelogenesis Imperfecta and Other Biomineralization Defects in fam20a and fam20c Null Mice. Vet Pathol. 49, 998-1017. |
| Posted On |
2012-11-20 |
| Science Writer |
Anne Murray |
Incidental Mutation