Phenotypic Mutation 'primurus' (pdf version)
Allele | primurus |
Mutation Type |
missense
|
Chromosome | 19 |
Coordinate | 25,160,973 bp (GRCm39) |
Base Change | T ⇒ C (forward strand) |
Gene |
Dock8
|
Gene Name | dedicator of cytokinesis 8 |
Synonym(s) | 1200017A24Rik, 5830472H07Rik, A130095G14Rik |
Chromosomal Location |
24,976,898-25,179,796 bp (+) (GRCm39)
|
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010] PHENOTYPE: Mice homozygous for inactivating mutations of this gene exhibit loss of marginal zone B cells, decrease in peritoneal B1 cells and peripheral naive T cells, failure of sustained antibody response after immunization, failure of germinal center persistence, and failure of B cell affinity maturation. [provided by MGI curators]
|
Accession Number | NCBI RefSeq: NM_033374; Ensembl: ENSMUST00000025831; MGI: 2149010
|
Mapped | Yes |
Amino Acid Change |
Serine changed to Proline
|
Institutional Source | Australian Phenomics Network |
Gene Model |
not available |
AlphaFold |
Q8C147 |
PDB Structure |
Crystal structure of the DHR-2 domain of DOCK8 in complex with Cdc42 (T17N mutant) [X-RAY DIFFRACTION]
|
SMART Domains |
Protein: ENSMUSP00000025831 Gene: ENSMUSG00000052085 AA Change: S1827P
Domain | Start | End | E-Value | Type |
Pfam:DUF3398
|
71 |
164 |
3.9e-25 |
PFAM |
Pfam:DOCK-C2
|
557 |
739 |
6.7e-49 |
PFAM |
low complexity region
|
786 |
803 |
N/A |
INTRINSIC |
low complexity region
|
1003 |
1020 |
N/A |
INTRINSIC |
low complexity region
|
1123 |
1138 |
N/A |
INTRINSIC |
low complexity region
|
1236 |
1246 |
N/A |
INTRINSIC |
low complexity region
|
1371 |
1383 |
N/A |
INTRINSIC |
Pfam:DHR-2
|
1534 |
2060 |
5e-210 |
PFAM |
|
Predicted Effect |
probably damaging
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
(Using ENSMUST00000025831)
|
Meta Mutation Damage Score |
Not available |
Is this an essential gene? |
Probably nonessential (E-score: 0.083) |
Phenotypic Category |
Autosomal Recessive |
Candidate Explorer Status |
loading ... |
Single pedigree Linkage Analysis Data
|
|
Penetrance | 100% |
Alleles Listed at MGI | All alleles(6) : Gene trapped(4) Chemically induced(2)
|
Lab Alleles |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
captain_morgan
|
APN |
19 |
25105076 |
critical splice donor site |
probably benign |
|
IGL00737:Dock8
|
APN |
19 |
25160340 |
missense |
probably benign |
0.00 |
IGL00755:Dock8
|
APN |
19 |
25028873 |
missense |
probably benign |
0.09 |
IGL00822:Dock8
|
APN |
19 |
25165773 |
nonsense |
probably null |
|
IGL00838:Dock8
|
APN |
19 |
25152823 |
nonsense |
probably null |
|
IGL01419:Dock8
|
APN |
19 |
25096816 |
missense |
probably benign |
0.08 |
IGL01456:Dock8
|
APN |
19 |
25096863 |
missense |
possibly damaging |
0.95 |
IGL01532:Dock8
|
APN |
19 |
25146805 |
missense |
probably damaging |
0.99 |
IGL01602:Dock8
|
APN |
19 |
25067252 |
splice site |
probably benign |
|
IGL01605:Dock8
|
APN |
19 |
25067252 |
splice site |
probably benign |
|
IGL01753:Dock8
|
APN |
19 |
25038656 |
splice site |
probably benign |
|
IGL01843:Dock8
|
APN |
19 |
25067292 |
missense |
probably benign |
0.02 |
IGL02032:Dock8
|
APN |
19 |
25107769 |
missense |
probably damaging |
0.99 |
IGL02073:Dock8
|
APN |
19 |
25178350 |
critical splice acceptor site |
probably null |
|
IGL02192:Dock8
|
APN |
19 |
25055569 |
critical splice donor site |
probably null |
|
IGL02402:Dock8
|
APN |
19 |
25055509 |
missense |
probably benign |
0.25 |
IGL02529:Dock8
|
APN |
19 |
25078290 |
nonsense |
probably null |
|
IGL02728:Dock8
|
APN |
19 |
25109584 |
missense |
probably benign |
|
IGL02739:Dock8
|
APN |
19 |
25165852 |
missense |
probably damaging |
1.00 |
IGL03037:Dock8
|
APN |
19 |
25063545 |
missense |
probably benign |
0.02 |
IGL03104:Dock8
|
APN |
19 |
25178384 |
nonsense |
probably null |
|
IGL03137:Dock8
|
APN |
19 |
25133312 |
missense |
probably benign |
0.19 |
IGL03365:Dock8
|
APN |
19 |
25077048 |
missense |
possibly damaging |
0.70 |
Defenseless
|
UTSW |
19 |
25028927 |
missense |
probably benign |
0.00 |
Guardate
|
UTSW |
19 |
25127195 |
missense |
probably benign |
|
hillock
|
UTSW |
19 |
25151697 |
critical splice donor site |
probably null |
|
Molehill
|
UTSW |
19 |
25107825 |
missense |
probably damaging |
1.00 |
Pap
|
UTSW |
19 |
25099805 |
missense |
probably benign |
0.31 |
Papilla
|
UTSW |
19 |
25055448 |
nonsense |
probably null |
|
snowdrop
|
UTSW |
19 |
25162305 |
critical splice donor site |
probably null |
|
warts_and_all
|
UTSW |
19 |
25146865 |
critical splice donor site |
probably null |
|
R0021:Dock8
|
UTSW |
19 |
25140411 |
missense |
probably benign |
0.01 |
R0147:Dock8
|
UTSW |
19 |
25096823 |
missense |
probably benign |
0.00 |
R0148:Dock8
|
UTSW |
19 |
25096823 |
missense |
probably benign |
0.00 |
R0294:Dock8
|
UTSW |
19 |
25165714 |
missense |
probably damaging |
1.00 |
R0537:Dock8
|
UTSW |
19 |
25148941 |
missense |
probably benign |
0.08 |
R0630:Dock8
|
UTSW |
19 |
25038524 |
missense |
probably benign |
0.10 |
R1163:Dock8
|
UTSW |
19 |
25028867 |
missense |
probably benign |
|
R1164:Dock8
|
UTSW |
19 |
25067391 |
missense |
probably benign |
0.44 |
R1471:Dock8
|
UTSW |
19 |
25178400 |
missense |
possibly damaging |
0.74 |
R1477:Dock8
|
UTSW |
19 |
25072914 |
missense |
possibly damaging |
0.95 |
R1633:Dock8
|
UTSW |
19 |
25028927 |
missense |
probably benign |
0.00 |
R1803:Dock8
|
UTSW |
19 |
25109599 |
missense |
probably benign |
0.00 |
R1822:Dock8
|
UTSW |
19 |
25138422 |
missense |
probably benign |
0.31 |
R1852:Dock8
|
UTSW |
19 |
25104492 |
missense |
probably benign |
0.45 |
R1916:Dock8
|
UTSW |
19 |
25038521 |
missense |
probably benign |
0.02 |
R1984:Dock8
|
UTSW |
19 |
25098545 |
missense |
probably null |
|
R2311:Dock8
|
UTSW |
19 |
25160368 |
missense |
possibly damaging |
0.93 |
R2341:Dock8
|
UTSW |
19 |
25177757 |
missense |
probably damaging |
0.99 |
R2483:Dock8
|
UTSW |
19 |
25057241 |
missense |
probably benign |
|
R3116:Dock8
|
UTSW |
19 |
25165858 |
missense |
probably benign |
0.00 |
R3157:Dock8
|
UTSW |
19 |
25127195 |
missense |
probably benign |
|
R3623:Dock8
|
UTSW |
19 |
25057241 |
missense |
probably benign |
|
R3624:Dock8
|
UTSW |
19 |
25057241 |
missense |
probably benign |
|
R3800:Dock8
|
UTSW |
19 |
25141716 |
missense |
probably benign |
0.08 |
R3844:Dock8
|
UTSW |
19 |
25042794 |
nonsense |
probably null |
|
R3895:Dock8
|
UTSW |
19 |
25028865 |
missense |
probably benign |
0.31 |
R3901:Dock8
|
UTSW |
19 |
25078269 |
missense |
possibly damaging |
0.69 |
R3959:Dock8
|
UTSW |
19 |
25162305 |
critical splice donor site |
probably null |
|
R4428:Dock8
|
UTSW |
19 |
25042754 |
missense |
probably benign |
0.00 |
R4428:Dock8
|
UTSW |
19 |
25177863 |
missense |
probably damaging |
0.98 |
R4429:Dock8
|
UTSW |
19 |
25042754 |
missense |
probably benign |
0.00 |
R4431:Dock8
|
UTSW |
19 |
25042754 |
missense |
probably benign |
0.00 |
R4545:Dock8
|
UTSW |
19 |
25165722 |
missense |
probably damaging |
1.00 |
R4839:Dock8
|
UTSW |
19 |
25146858 |
missense |
probably benign |
0.00 |
R4897:Dock8
|
UTSW |
19 |
25159001 |
missense |
probably benign |
0.00 |
R4939:Dock8
|
UTSW |
19 |
25099764 |
missense |
probably damaging |
1.00 |
R4995:Dock8
|
UTSW |
19 |
25135747 |
missense |
probably benign |
0.02 |
R5035:Dock8
|
UTSW |
19 |
25063571 |
missense |
probably damaging |
0.99 |
R5294:Dock8
|
UTSW |
19 |
25038517 |
missense |
probably benign |
0.01 |
R5324:Dock8
|
UTSW |
19 |
25140458 |
missense |
probably benign |
0.17 |
R5478:Dock8
|
UTSW |
19 |
25057186 |
missense |
probably benign |
|
R5704:Dock8
|
UTSW |
19 |
25151586 |
missense |
probably damaging |
1.00 |
R5724:Dock8
|
UTSW |
19 |
25099785 |
missense |
probably damaging |
1.00 |
R5745:Dock8
|
UTSW |
19 |
25107761 |
missense |
probably benign |
0.02 |
R5864:Dock8
|
UTSW |
19 |
25038584 |
missense |
probably damaging |
0.99 |
R5870:Dock8
|
UTSW |
19 |
25109490 |
missense |
probably benign |
|
R5893:Dock8
|
UTSW |
19 |
25099811 |
missense |
probably damaging |
1.00 |
R5954:Dock8
|
UTSW |
19 |
25148983 |
missense |
probably damaging |
1.00 |
R6087:Dock8
|
UTSW |
19 |
25138438 |
missense |
probably benign |
0.00 |
R6223:Dock8
|
UTSW |
19 |
25138416 |
missense |
probably benign |
0.00 |
R6391:Dock8
|
UTSW |
19 |
25072914 |
missense |
possibly damaging |
0.95 |
R6759:Dock8
|
UTSW |
19 |
25104848 |
missense |
probably damaging |
0.99 |
R6786:Dock8
|
UTSW |
19 |
25160386 |
missense |
possibly damaging |
0.49 |
R6794:Dock8
|
UTSW |
19 |
25099805 |
missense |
probably benign |
0.31 |
R6818:Dock8
|
UTSW |
19 |
25146865 |
critical splice donor site |
probably null |
|
R6885:Dock8
|
UTSW |
19 |
25124742 |
missense |
possibly damaging |
0.95 |
R6908:Dock8
|
UTSW |
19 |
25165746 |
missense |
probably damaging |
1.00 |
R6923:Dock8
|
UTSW |
19 |
25072970 |
missense |
probably benign |
|
R7001:Dock8
|
UTSW |
19 |
25077041 |
missense |
probably benign |
|
R7141:Dock8
|
UTSW |
19 |
25158984 |
missense |
probably null |
0.75 |
R7203:Dock8
|
UTSW |
19 |
25158927 |
missense |
probably damaging |
1.00 |
R7257:Dock8
|
UTSW |
19 |
25104449 |
missense |
probably benign |
0.08 |
R7296:Dock8
|
UTSW |
19 |
25162245 |
missense |
probably benign |
0.00 |
R7538:Dock8
|
UTSW |
19 |
25135782 |
missense |
probably damaging |
1.00 |
R7555:Dock8
|
UTSW |
19 |
25152764 |
missense |
probably damaging |
0.99 |
R7641:Dock8
|
UTSW |
19 |
25151697 |
critical splice donor site |
probably null |
|
R7764:Dock8
|
UTSW |
19 |
25074899 |
missense |
probably benign |
|
R7859:Dock8
|
UTSW |
19 |
25160934 |
missense |
probably damaging |
1.00 |
R7864:Dock8
|
UTSW |
19 |
25140864 |
missense |
possibly damaging |
0.95 |
R8090:Dock8
|
UTSW |
19 |
25131606 |
missense |
probably damaging |
1.00 |
R8160:Dock8
|
UTSW |
19 |
25124711 |
missense |
probably damaging |
1.00 |
R8287:Dock8
|
UTSW |
19 |
25107825 |
missense |
probably damaging |
1.00 |
R8295:Dock8
|
UTSW |
19 |
25100600 |
missense |
probably benign |
0.04 |
R8443:Dock8
|
UTSW |
19 |
25133281 |
missense |
probably benign |
0.04 |
R8537:Dock8
|
UTSW |
19 |
25107870 |
missense |
probably benign |
0.00 |
R8673:Dock8
|
UTSW |
19 |
25160867 |
missense |
probably damaging |
0.96 |
R8709:Dock8
|
UTSW |
19 |
25055448 |
nonsense |
probably null |
|
R8834:Dock8
|
UTSW |
19 |
25140834 |
missense |
probably benign |
0.16 |
R8991:Dock8
|
UTSW |
19 |
25165731 |
missense |
possibly damaging |
0.82 |
R9292:Dock8
|
UTSW |
19 |
25160995 |
splice site |
probably benign |
|
R9509:Dock8
|
UTSW |
19 |
25072985 |
missense |
probably benign |
0.00 |
R9526:Dock8
|
UTSW |
19 |
25165739 |
missense |
probably benign |
0.10 |
R9622:Dock8
|
UTSW |
19 |
25098545 |
missense |
probably null |
|
R9634:Dock8
|
UTSW |
19 |
25169585 |
missense |
probably damaging |
1.00 |
R9654:Dock8
|
UTSW |
19 |
25124710 |
missense |
probably damaging |
1.00 |
R9670:Dock8
|
UTSW |
19 |
25148926 |
missense |
probably null |
0.01 |
R9699:Dock8
|
UTSW |
19 |
25133388 |
critical splice donor site |
probably null |
|
R9726:Dock8
|
UTSW |
19 |
25154374 |
missense |
probably damaging |
0.97 |
R9765:Dock8
|
UTSW |
19 |
25146832 |
missense |
possibly damaging |
0.94 |
X0027:Dock8
|
UTSW |
19 |
25138493 |
missense |
probably benign |
|
Z1177:Dock8
|
UTSW |
19 |
25133336 |
missense |
probably benign |
0.16 |
Z1177:Dock8
|
UTSW |
19 |
25109487 |
missense |
probably benign |
0.05 |
|
Mode of Inheritance |
Autosomal Recessive |
Local Stock | None |
Repository | Australian PhenomeBank: 4498
|
Last Updated |
2019-05-26 8:06 AM
by Diantha La Vine
|
Record Created |
2011-01-12 2:36 PM
by Nora G. Smart
|
Record Posted |
2011-01-12 |
Phenotypic Description |
The primurus mutation was identified while screening N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice for a failure to mount long-lived, high-affinity antibody responses despite a relatively normal initial wave of antibody production. Primurus is allelic to captain morgan. For more information on the phenotype of primurus mice, please see the record for captain morgan.
|
Nature of Mutation | The primurus mutation was mapped to Chromosome 19. Sequencing B cell–expressed transcripts in the minimal 4.5 Mb interval identified a T to C transition at position 5601 of the Dock8 transcript using Genbank record NM_028785.3, in exon 43 of 48 total exons.
5586 AAGCTCCCGGAGATCTCACATAGACTAGAGGGA
1822 -K--L--P--E--I--S--H--R--L--E--G-
|
The mutated nucleotide is indicated in red lettering and causes a serine to proline change at amino acid 1827 of the encoded protein.
|
Illustration of Mutations in
Gene & Protein |
|
---|
Protein Prediction |
The primurus mutation alters a highly conserved amino acid in the DHR-2 domain (Figure 1). In the structure of DOCK9 in complex with Cdc42 (1), this conserved serine lies in the DHR-2 lobe B α-helix 6, which forms part of the Cdc42-binding site and provides four Cdc42 contact residues. The pri substitution of Ser1827 to Pro1827 would be expected to break this α-helical structure and interfere with the guanine-exchange factor activity of the DHR-2 domain.
|
Putative Mechanism | The phenotypes of primurus animals are identical to those found in captain morgan mice, suggesting that primurus is a strong loss of function allele.
For more information on Dock8, please see the record for captain morgan.
|
Primers |
Primers cannot be located by automatic search.
|
Genotyping | Genotyping protocols are from the Australian PhenomeBank.
Primurus
|
References | 1. Yang, J., Zhang, Z., Roe, S. M., Marshall, C. J., and Barford, D. (2009) Activation of Rho GTPases by DOCK Exchange Factors is Mediated by a Nucleotide Sensor. Science. 325, 1398-1402.
|
Science Writers | Nora G. Smart |
Illustrators | Diantha La Vine |
Authors | Katrina L Randall, Teresa Lambe, Andy L Johnson, Bebhinn Treanor, Edyta Kucharska, Heather Domaschenz, Belinda Whittle, Lina E Tze, Anselm Enders, Tanya L Crockford, Tiphaine Bouriez-Jones, Duncan Alston, Jason G Cyster, Michael J Lenardo, Fabienne Mackay, Elissa K Deenick, Stuart G Tangye, Tyani D Chan, Tahra Camidge, Robert Brink, Carola G Vinuesa, Facundo D Batista, Richard J Cornall, Christopher C Goodnow |