Mutagenetix > Incidental Mutations

Incidental Mutation 'G5030:Adam18'

499

Institutional Source

Beutler Lab

Gene Symbol

Adam18

Ensembl Gene

ENSMUSG00000031552

Gene Name

a disintegrin and metallopeptidase domain 18

Synonyms

Adam27, 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

Chromosome

Chromosomal Location

24602246-24674755 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to G at 24651856 bp

Zygosity

Homozygous

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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

0.3016

Coding Region Coverage

1x: 81.1%
3x: 60.2%

Het Detection Efficiency

35.6%

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
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
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		noncoding transcript	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

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R7194:Adam18	UTSW	8	24651852	missense	possibly damaging	0.67
R7226:Adam18	UTSW	8	24647808	missense	probably damaging	1.00
R7266:Adam18	UTSW	8	24667623	missense	probably benign	0.00
R7397:Adam18	UTSW	8	24646305	missense	possibly damaging	0.48
R7575:Adam18	UTSW	8	24625857	missense	possibly damaging	0.50
R7786:Adam18	UTSW	8	24611118	missense	probably benign	0.00
R7872:Adam18	UTSW	8	24611100	missense	probably benign	0.00
R7955:Adam18	UTSW	8	24611100	missense	probably benign	0.00
R8069:Adam18	UTSW	8	24628230	missense	possibly damaging	0.96

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 On

2010-10-26