Incidental Mutation 'E2594:Adamts17'
ID 5
Institutional Source Beutler Lab
Gene Symbol Adamts17
Ensembl Gene ENSMUSG00000058145
Gene Name ADAM metallopeptidase with thrombospondin type 1 motif 17
Synonyms AU023434
Accession Numbers
Essential gene? Probably non essential (E-score: 0.073) question?
Stock # E2594 of strain daniel_gray
Quality Score
Status Validated
Chromosome 7
Chromosomal Location 66489483-66802919 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 66654098 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Serine to Glycine at position 443 (S443G)
Ref Sequence ENSEMBL: ENSMUSP00000103102 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000098382] [ENSMUST00000107478]
AlphaFold E9Q4D1
Predicted Effect probably damaging
Transcript: ENSMUST00000098382
AA Change: S443G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000095984
Gene: ENSMUSG00000058145
AA Change: S443G

DomainStartEndE-ValueType
signal peptide 1 26 N/A INTRINSIC
Pfam:Pep_M12B_propep 35 179 2.9e-25 PFAM
Pfam:Reprolysin_5 228 422 3.1e-15 PFAM
Pfam:Reprolysin_2 248 440 6.1e-13 PFAM
Pfam:Reprolysin_3 252 398 2.2e-12 PFAM
Pfam:Reprolysin_4 328 446 7.1e-10 PFAM
Pfam:Reprolysin 334 450 2e-18 PFAM
Blast:ACR 454 533 3e-12 BLAST
TSP1 544 596 2.2e-15 SMART
Pfam:ADAM_spacer1 698 808 6.4e-30 PFAM
TSP1 829 887 1.81e-1 SMART
TSP1 889 942 1.15e-4 SMART
TSP1 949 993 4.05e-5 SMART
TSP1 1000 1054 2.91e-6 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000107478
AA Change: S443G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000103102
Gene: ENSMUSG00000058145
AA Change: S443G

DomainStartEndE-ValueType
signal peptide 1 26 N/A INTRINSIC
Pfam:Pep_M12B_propep 34 180 3.1e-23 PFAM
Pfam:Reprolysin_5 228 424 3.2e-15 PFAM
Pfam:Reprolysin_2 248 440 5.9e-11 PFAM
Pfam:Reprolysin_3 252 398 6e-12 PFAM
Pfam:Reprolysin_4 328 446 6.8e-10 PFAM
Pfam:Reprolysin 334 450 4.3e-21 PFAM
Blast:ACR 454 533 3e-12 BLAST
TSP1 544 596 2.2e-15 SMART
Pfam:ADAM_spacer1 700 781 2.2e-16 PFAM
TSP1 802 860 1.81e-1 SMART
TSP1 862 915 1.15e-4 SMART
TSP1 922 966 4.05e-5 SMART
TSP1 973 1027 2.91e-6 SMART
Pfam:PLAC 1046 1080 1.1e-10 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147880
Predicted Effect noncoding transcript
Transcript: ENSMUST00000148538
Meta Mutation Damage Score 0.2220 question?
Coding Region Coverage
  • 1x: 80.5%
  • 3x: 47.5%
Validation Efficiency 94% (32/34)
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 ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. [provided by RefSeq, May 2016]
Allele List at MGI

All alleles(3) : Targeted, other(2) Gene trapped(1)

Other mutations in this stock
Total: 3 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Atad3a G A 4: 155,835,390 (GRCm39) probably benign Het
Misp3 G A 8: 84,737,331 (GRCm39) probably benign Het
Rigi C T 4: 40,235,282 (GRCm39) W69* probably null Het
Other mutations in Adamts17
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00708:Adamts17 APN 7 66,618,650 (GRCm39) missense probably damaging 1.00
IGL00950:Adamts17 APN 7 66,770,660 (GRCm39) missense possibly damaging 0.69
IGL01532:Adamts17 APN 7 66,558,349 (GRCm39) missense probably damaging 1.00
IGL01591:Adamts17 APN 7 66,654,144 (GRCm39) missense probably damaging 1.00
IGL01602:Adamts17 APN 7 66,538,159 (GRCm39) missense probably benign 0.29
IGL01640:Adamts17 APN 7 66,679,428 (GRCm39) missense probably damaging 0.98
IGL01686:Adamts17 APN 7 66,490,037 (GRCm39) missense probably benign 0.06
IGL01747:Adamts17 APN 7 66,701,759 (GRCm39) missense probably damaging 1.00
IGL02081:Adamts17 APN 7 66,711,858 (GRCm39) missense probably damaging 1.00
IGL02152:Adamts17 APN 7 66,774,748 (GRCm39) missense probably benign 0.01
IGL02264:Adamts17 APN 7 66,697,207 (GRCm39) splice site probably null
IGL02457:Adamts17 APN 7 66,677,562 (GRCm39) missense probably damaging 0.99
IGL02519:Adamts17 APN 7 66,774,721 (GRCm39) missense possibly damaging 0.82
IGL02530:Adamts17 APN 7 66,559,124 (GRCm39) missense probably damaging 1.00
IGL02649:Adamts17 APN 7 66,499,626 (GRCm39) splice site probably benign
IGL02711:Adamts17 APN 7 66,701,788 (GRCm39) splice site probably benign
IGL03006:Adamts17 APN 7 66,728,095 (GRCm39) missense possibly damaging 0.53
IGL03203:Adamts17 APN 7 66,711,856 (GRCm39) missense probably damaging 1.00
IGL03343:Adamts17 APN 7 66,725,064 (GRCm39) missense probably damaging 1.00
BB007:Adamts17 UTSW 7 66,499,547 (GRCm39) missense probably damaging 0.96
BB017:Adamts17 UTSW 7 66,499,547 (GRCm39) missense probably damaging 0.96
R0380:Adamts17 UTSW 7 66,799,792 (GRCm39) missense probably benign 0.00
R0416:Adamts17 UTSW 7 66,565,646 (GRCm39) splice site probably null
R0635:Adamts17 UTSW 7 66,558,353 (GRCm39) missense probably damaging 1.00
R1083:Adamts17 UTSW 7 66,797,322 (GRCm39) missense probably damaging 1.00
R1476:Adamts17 UTSW 7 66,725,091 (GRCm39) missense probably damaging 1.00
R1728:Adamts17 UTSW 7 66,799,704 (GRCm39) nonsense probably null
R1729:Adamts17 UTSW 7 66,799,704 (GRCm39) nonsense probably null
R1763:Adamts17 UTSW 7 66,797,463 (GRCm39) missense probably damaging 1.00
R1784:Adamts17 UTSW 7 66,799,704 (GRCm39) nonsense probably null
R1905:Adamts17 UTSW 7 66,697,220 (GRCm39) nonsense probably null
R1938:Adamts17 UTSW 7 66,774,820 (GRCm39) missense probably damaging 1.00
R3106:Adamts17 UTSW 7 66,774,820 (GRCm39) missense probably damaging 1.00
R3796:Adamts17 UTSW 7 66,489,662 (GRCm39) splice site probably null
R3849:Adamts17 UTSW 7 66,490,215 (GRCm39) missense possibly damaging 0.92
R3850:Adamts17 UTSW 7 66,490,215 (GRCm39) missense possibly damaging 0.92
R3945:Adamts17 UTSW 7 66,770,687 (GRCm39) missense probably benign
R4519:Adamts17 UTSW 7 66,490,314 (GRCm39) missense probably damaging 0.99
R4554:Adamts17 UTSW 7 66,677,641 (GRCm39) missense probably damaging 1.00
R4555:Adamts17 UTSW 7 66,677,641 (GRCm39) missense probably damaging 1.00
R4556:Adamts17 UTSW 7 66,677,641 (GRCm39) missense probably damaging 1.00
R4557:Adamts17 UTSW 7 66,677,641 (GRCm39) missense probably damaging 1.00
R4700:Adamts17 UTSW 7 66,691,636 (GRCm39) missense probably damaging 1.00
R4752:Adamts17 UTSW 7 66,654,218 (GRCm39) missense probably damaging 0.96
R5019:Adamts17 UTSW 7 66,711,818 (GRCm39) nonsense probably null
R5438:Adamts17 UTSW 7 66,538,165 (GRCm39) missense probably benign 0.30
R5444:Adamts17 UTSW 7 66,691,647 (GRCm39) missense probably benign 0.02
R5673:Adamts17 UTSW 7 66,691,555 (GRCm39) missense probably damaging 1.00
R6326:Adamts17 UTSW 7 66,770,636 (GRCm39) missense probably benign 0.05
R6964:Adamts17 UTSW 7 66,654,101 (GRCm39) missense probably benign 0.00
R6964:Adamts17 UTSW 7 66,559,148 (GRCm39) missense possibly damaging 0.93
R7129:Adamts17 UTSW 7 66,770,758 (GRCm39) missense probably damaging 1.00
R7317:Adamts17 UTSW 7 66,490,304 (GRCm39) nonsense probably null
R7355:Adamts17 UTSW 7 66,725,052 (GRCm39) missense
R7386:Adamts17 UTSW 7 66,618,597 (GRCm39) missense probably benign 0.25
R7407:Adamts17 UTSW 7 66,697,304 (GRCm39) nonsense probably null
R7432:Adamts17 UTSW 7 66,701,665 (GRCm39) missense
R7782:Adamts17 UTSW 7 66,774,802 (GRCm39) missense probably damaging 1.00
R7817:Adamts17 UTSW 7 66,559,224 (GRCm39) missense probably damaging 0.99
R7930:Adamts17 UTSW 7 66,499,547 (GRCm39) missense probably damaging 0.96
R7993:Adamts17 UTSW 7 66,499,612 (GRCm39) missense possibly damaging 0.90
R8178:Adamts17 UTSW 7 66,499,464 (GRCm39) missense possibly damaging 0.46
R8962:Adamts17 UTSW 7 66,725,057 (GRCm39) missense probably damaging 1.00
R9095:Adamts17 UTSW 7 66,654,117 (GRCm39) missense probably damaging 1.00
R9111:Adamts17 UTSW 7 66,489,648 (GRCm39) missense probably damaging 0.96
R9303:Adamts17 UTSW 7 66,489,645 (GRCm39) missense probably damaging 0.99
R9305:Adamts17 UTSW 7 66,489,645 (GRCm39) missense probably damaging 0.99
R9505:Adamts17 UTSW 7 66,774,683 (GRCm39) missense probably benign 0.00
R9668:Adamts17 UTSW 7 66,797,438 (GRCm39) missense possibly damaging 0.61
X0022:Adamts17 UTSW 7 66,691,649 (GRCm39) missense probably benign 0.44
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 1428 of the Adamts17 transcript, in exon 10 of 22 total exons (Figure 1). Multiple isoforms of Adamts17 are displayed on Ensembl
 
1413 CTCAAATCCAAAGTCAGTACATGTTTACTGATC
438  -L--K--S--K--V--S--T--C--L--L--I-
 
The mutated nucleotide is indicated in red lettering, and causes a serine to glycine substitution at amino acid 443 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 2).
Protein Function and Prediction
The 1095 amino acid mouse ADAMTS17 protein is an uncharacterized member of a large family of secreted zinc-dependent metalloproteases known as the ADAMTS (a disintegrin and metalloprotease domain, with thrombospondin type-1 repeats) family. ADAMTS proteins belong to the adamalysin family of metalloproteases, which includes snake venom metalloproteases and ADAMs. ADAMTS proteins are predicted to interact with the extracellular matrix (ECM) and play a wide role in normal and pathological processes (1)
 
ADAMTS members are multi-domain proteins typically containing an N-terminal signal sequence followed by a cleavable prodomain that typically contains three conserved cysteine residues, a metalloprotease domain (HEXGHXXGXXHD) containing a zinc coordinating catalytic sequence and a conserved methionine that forms a characteristic “Met” turn (Figure 3; NCBI pfam01421), a disintegrin-like domain, a single thrombospondin (TSP) repeat, a cysteine-rich domain, a spacer region, and a highly variable number of additional TSP repeats (three in ADAMTS17). In addition to these characteristic domains, ADAMTS17 contains a C-terminal PLAC (Protease and LACunin) domain found in a subset of the ADAMTS proteins. This domain is characterized by six conserved cysteine residues, and is found in some proprotein convertases (2).
 
The S443G alteration occurs near the C-terminal end of the ADAMTS17 metalloprotease domain, and is predicted to be benign by the PolyPhen program. 
References
Posted On 2009-10-27