Incidental Mutation 'G5030:Adam18'
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ID499
Institutional Source Beutler Lab
Gene Symbol Adam18
Ensembl Gene ENSMUSG00000031552
Gene Namea disintegrin and metallopeptidase domain 18
SynonymsAdam27, Dtgn3
Accession Numbers

Genbank: NM_010084

Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #G5030 (G3) of strain 560
Quality Score
Status Validated
Chromosome8
Chromosomal Location24602246-24674755 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to G at 24651856 bp
ZygosityHomozygous
Amino Acid Change Leucine to Phenylalanine at position 232 (L232F)
Ref Sequence ENSEMBL: ENSMUSP00000033957 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000033957] [ENSMUST00000173833]
Predicted Effect probably benign
Transcript: ENSMUST00000033957
AA Change: L232F

PolyPhen 2 Score 0.243 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000033957
Gene: ENSMUSG00000031552
AA Change: L232F

DomainStartEndE-ValueType
Pfam:Pep_M12B_propep 15 140 1.7e-25 PFAM
Pfam:Reprolysin 180 377 1.1e-57 PFAM
DISIN 396 474 1.03e-35 SMART
ACR 475 613 1.12e-51 SMART
transmembrane domain 684 703 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000173833
AA Change: L232F

PolyPhen 2 Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000133378
Gene: ENSMUSG00000031552
AA Change: L232F

DomainStartEndE-ValueType
Pfam:Pep_M12B_propep 15 140 9.5e-35 PFAM
Pfam:Reprolysin 180 378 7.7e-56 PFAM
DISIN 396 474 1.03e-35 SMART
ACR 475 613 1.12e-51 SMART
Meta Mutation Damage Score 0.13 question?
Coding Region Coverage
  • 1x: 81.1%
  • 3x: 60.2%
Het Detection Efficiency35.6%
Validation Efficiency 87% (206/237)
MGI Phenotype FUNCTION: This gene encodes a member of a disintegrin and metalloprotease (ADAM) family of endoproteases that play important roles in various biological processes including cell signaling, adhesion and migration. This gene is expressed in a regulated fashion during early stages of spermatogenesis. The encoded preproprotein undergoes proteolytic processing to generate a mature, functional protein. This gene is located in a cluster of related ADAM genes on chromosome 8. [provided by RefSeq, May 2016]
PHENOTYPE: Homozygous mutant mice exhibit enhanced motor coordination during inverted screen testing when compared with that of controls. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Targeted, other(1)

Other mutations in this stock
Total: 30 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca8a T A 11: 110,070,339 I585F probably damaging Het
Atp13a4 A G 16: 29,455,488 I385T probably damaging Homo
Ccdc17 T A 4: 116,598,502 S277T probably benign Het
Ccng1 A G 11: 40,753,802 probably benign Het
Ces1f T C 8: 93,274,219 D99G probably benign Het
Clec16a G A 16: 10,571,561 R187Q probably damaging Homo
Cryl1 C T 14: 57,342,138 probably benign Het
Cryzl2 C T 1: 157,465,010 Q48* probably null Het
Dtx4 A G 19: 12,469,579 L583P probably benign Het
Ephx4 A T 5: 107,429,827 D339V probably damaging Het
Eri2 A T 7: 119,786,378 V300E possibly damaging Het
F3 T A 3: 121,724,999 N37K probably damaging Homo
Fpr1 A T 17: 17,876,806 L307H probably damaging Het
Fv1 T A 4: 147,869,161 N61K possibly damaging Het
Gm5548 T C 3: 113,054,196 Homo
Il1r1 A G 1: 40,313,163 K498E possibly damaging Homo
Myh11 T C 16: 14,250,579 I192M probably damaging Homo
Nckap5 T C 1: 126,025,854 K923R probably damaging Het
Nmbr A T 10: 14,767,003 Y102F possibly damaging Het
Olfr790 A G 10: 129,501,537 T218A probably benign Homo
Pde1a C T 2: 79,887,836 probably benign Het
Pex6 T C 17: 46,715,456 probably benign Het
Rtn2 T C 7: 19,293,174 S305P probably damaging Homo
Saal1 G A 7: 46,692,783 T412I probably damaging Homo
Slc46a2 A T 4: 59,913,867 I352N probably damaging Het
Trim37 A T 11: 87,143,141 H99L probably damaging Het
Tubgcp4 C T 2: 121,184,334 R242C probably damaging Het
Twf2 C A 9: 106,206,942 L27I possibly damaging Het
Usp40 A T 1: 87,994,219 H307Q probably damaging Het
Zfhx3 T G 8: 108,951,459 V3047G possibly damaging Het
Other mutations in Adam18
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00470:Adam18 APN 8 24628133 missense probably damaging 1.00
IGL01649:Adam18 APN 8 24614896 missense possibly damaging 0.82
IGL02212:Adam18 APN 8 24637179 missense probably benign 0.02
IGL02455:Adam18 APN 8 24651848 missense probably damaging 0.96
IGL02525:Adam18 APN 8 24611044 missense probably benign 0.00
IGL02525:Adam18 APN 8 24641767 splice site probably benign
IGL02966:Adam18 APN 8 24611149 splice site probably benign
IGL03136:Adam18 APN 8 24641836 missense probably damaging 1.00
R0135:Adam18 UTSW 8 24665542 missense possibly damaging 0.71
R0280:Adam18 UTSW 8 24674054 missense probably benign 0.06
R0389:Adam18 UTSW 8 24629637 splice site probably null
R0390:Adam18 UTSW 8 24674054 missense probably benign 0.06
R0443:Adam18 UTSW 8 24629637 splice site probably null
R0479:Adam18 UTSW 8 24651822 missense probably benign
R0578:Adam18 UTSW 8 24641847 missense possibly damaging 0.82
R0645:Adam18 UTSW 8 24672120 nonsense probably null
R0881:Adam18 UTSW 8 24672143 splice site probably benign
R0885:Adam18 UTSW 8 24651786 missense probably damaging 1.00
R0973:Adam18 UTSW 8 24647853 missense probably benign 0.01
R0973:Adam18 UTSW 8 24647853 missense probably benign 0.01
R0974:Adam18 UTSW 8 24647853 missense probably benign 0.01
R1005:Adam18 UTSW 8 24665514 missense probably benign 0.05
R1356:Adam18 UTSW 8 24668595 splice site probably benign
R1510:Adam18 UTSW 8 24625831 missense probably benign 0.01
R1552:Adam18 UTSW 8 24646361 missense probably benign
R1568:Adam18 UTSW 8 24647783 splice site probably null
R1639:Adam18 UTSW 8 24652152 missense probably benign 0.00
R1968:Adam18 UTSW 8 24646447 missense probably benign 0.32
R2029:Adam18 UTSW 8 24650877 missense probably damaging 1.00
R2058:Adam18 UTSW 8 24672066 splice site probably benign
R2211:Adam18 UTSW 8 24628155 missense probably damaging 0.96
R2237:Adam18 UTSW 8 24646287 missense probably benign 0.01
R2238:Adam18 UTSW 8 24646287 missense probably benign 0.01
R2239:Adam18 UTSW 8 24646287 missense probably benign 0.01
R2518:Adam18 UTSW 8 24637141 missense probably damaging 1.00
R3122:Adam18 UTSW 8 24628232 missense possibly damaging 0.74
R3426:Adam18 UTSW 8 24667604 missense probably damaging 1.00
R3428:Adam18 UTSW 8 24667604 missense probably damaging 1.00
R3967:Adam18 UTSW 8 24629710 missense probably benign 0.12
R4833:Adam18 UTSW 8 24674101 missense probably benign 0.01
R4965:Adam18 UTSW 8 24641811 missense probably damaging 1.00
R5249:Adam18 UTSW 8 24625852 missense probably benign 0.00
R5534:Adam18 UTSW 8 24665514 missense probably benign 0.05
R5920:Adam18 UTSW 8 24674075 missense probably damaging 1.00
R6329:Adam18 UTSW 8 24614827 missense probably damaging 1.00
R6450:Adam18 UTSW 8 24629675 missense probably benign 0.05
R6479:Adam18 UTSW 8 24629665 missense probably benign 0.29
R6516:Adam18 UTSW 8 24674687 missense probably damaging 1.00
R6603:Adam18 UTSW 8 24665502 missense possibly damaging 0.63
Nature of Mutation
DNA sequencing using the SOLiD technique identified a G to C transversion at position 754 of the Adam18 transcript in exon 9 of 20 total exons. Two transcripts of the Adam18 gene are displayed on Ensembl and Vega. The mutated nucleotide causes a leucine to phenylalanine substitution at amino acid 232 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction

The Adam18 gene encodes a 763 amino acid disintegrin and metalloproteinase domain-containing protein 18 (Uniprot Q9R157). ADAMs are a family of cell surface proteins with a domain structure composed of a signal sequence, a prodomain with a cysteine switch, a metalloproteinase-like domain, a disintegrin-like domain, a cysteine-rich domain, a transmembrane domain, and a C-terminal cytoplasmic domain. These proteins function as proteases to cleave a variety of substrates, but ADAM18 seems to be non-catalytic as its zinc-binding motif contains a variant amino acid. ADAM18 is expressed specifically in the testis, and may be involved in spermatogenesis and fertilization. A tripeptide motif (ECD) within the disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.

 

The L232F change is located in the peptidase domain, and is predicted to be possibly damaging by the PolyPhen program (see report).
Posted On2010-10-26