Mutagenetix > Incidental Mutation

Incidental Mutation 'R2020:Adam17'

223871

Institutional Source

Beutler Lab

Gene Symbol

Adam17

Ensembl Gene

ENSMUSG00000052593

Gene Name

a disintegrin and metallopeptidase domain 17

Synonyms

CD156b, Tace

MMRRC Submission

040029-MU

Accession Numbers

Genbank: NM_009615; MGI: 1096335

Essential gene?

Probably essential (E-score: 0.891) question?

Stock #

R2020 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

21323509-21373632 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 21349875 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Cysteine at position 177 (R177C)

Ref Sequence

ENSEMBL: ENSMUSP00000136407 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000064536] [ENSMUST00000101551] [ENSMUST00000127974] [ENSMUST00000142092] [ENSMUST00000145118] [ENSMUST00000232107] [ENSMUST00000232526]

AlphaFold

Q9Z0F8

Predicted Effect

probably damaging
Transcript: ENSMUST00000064536
AA Change: R177C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000067953
Gene: ENSMUSG00000052593
AA Change: R177C

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Pep_M12B_propep	28	167	1.1e-11	PFAM
Pfam:Reprolysin_5	221	451	6.7e-37	PFAM
Pfam:Reprolysin_4	221	469	3.2e-24	PFAM
Pfam:Reprolysin_2	244	464	8.8e-29	PFAM
Pfam:Reprolysin_3	248	416	1.2e-12	PFAM
Pfam:Reprolysin	383	474	3.1e-9	PFAM
DISIN	484	561	6.27e-26	SMART
PDB:2M2F\|A	581	642	4e-32	PDB
transmembrane domain	672	694	N/A	INTRINSIC
low complexity region	739	755	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000101551
AA Change: R177C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000099087
Gene: ENSMUSG00000052593
AA Change: R177C

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Pep_M12B_propep	31	167	9.7e-15	PFAM
Pfam:Reprolysin_5	221	470	5e-34	PFAM
Pfam:Reprolysin_4	221	488	6.1e-20	PFAM
Pfam:Reprolysin_2	264	483	2.6e-34	PFAM
Pfam:Reprolysin_3	267	435	2.8e-14	PFAM
Pfam:Reprolysin	330	493	5.3e-9	PFAM
DISIN	503	580	6.27e-26	SMART
Pfam:ADAM17_MPD	600	661	1e-23	PFAM
transmembrane domain	691	713	N/A	INTRINSIC
low complexity region	758	774	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000127974
AA Change: R177C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000136677
Gene: ENSMUSG00000052593
AA Change: R177C

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Pep_M12B_propep	25	167	9.1e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000142092

SMART Domains

Protein: ENSMUSP00000136255
Gene: ENSMUSG00000052593

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
low complexity region	35	47	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000145118
AA Change: R177C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000136407
Gene: ENSMUSG00000052593
AA Change: R177C

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Pep_M12B_propep	28	167	7.5e-12	PFAM
Pfam:Reprolysin_5	221	451	4.2e-37	PFAM
Pfam:Reprolysin_4	221	469	2e-24	PFAM
Pfam:Reprolysin_2	244	464	5.6e-29	PFAM
Pfam:Reprolysin_3	248	416	7.8e-13	PFAM
Pfam:Reprolysin	381	474	2.2e-9	PFAM
DISIN	484	561	6.27e-26	SMART
PDB:2M2F\|A	581	638	5e-29	PDB

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000158372

Predicted Effect

probably benign
Transcript: ENSMUST00000232107

Predicted Effect

probably benign
Transcript: ENSMUST00000232526

Meta Mutation Damage Score

0.6201

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 93.6%

Validation Efficiency

99% (87/88)

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. The encoded preproprotein undergoes proteolytic processing to generate a mature enzyme that is involved in the proteolytic release of membrane-bound proteins in a process called ectodomain shedding. Mice lacking the encoded protein die in utero or fail to survive beyond one week of age. Alternative splicing results in multiple transcript variants encoding different isoforms, some of which may undergo similar processing. [provided by RefSeq, May 2016]
PHENOTYPE: Most mice homozygous for targeted mutations that inactivate the gene die perinatally with stunted vibrissae and open eyelids. Survivors display various degrees of eye degeneration, perturbed hair coats, curly vibrissae, and irregular pigmentation patterns. Histological analysis of fetuses reveal defects in epithelial cell maturation and organization in multiple organs. [provided by MGI curators]

Allele List at MGI

All alleles(13) : Targeted, knock-out(2) Targeted, other(3) Gene trapped(8)

Other mutations in this stock

Total: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1600012P17Rik	C	A	1: 158,968,912		noncoding transcript	Het
9530053A07Rik	T	C	7: 28,155,594	S1882P	probably benign	Het
Ak7	G	A	12: 105,745,332		probably null	Het
Akap9	T	C	5: 3,961,967	V890A	probably damaging	Het
Alg6	A	G	4: 99,738,132	N59S	probably damaging	Het
Alkbh5	G	T	11: 60,538,549	A43S	probably benign	Het
Anxa2	C	A	9: 69,483,817	D162E	probably damaging	Het
Arap1	A	G	7: 101,401,518	H1136R	probably benign	Het
Arhgap18	A	G	10: 26,854,904	R121G	probably benign	Het
Arhgef4	A	T	1: 34,723,810	T716S	unknown	Het
Atg2a	T	C	19: 6,250,269		probably null	Het
Ccdc27	T	C	4: 154,033,313	I480V	probably null	Het
Cdipt	T	C	7: 126,976,933	V20A	possibly damaging	Het
Cgrrf1	C	T	14: 46,830,445		probably benign	Het
Chd7	G	A	4: 8,855,226	V2152I	probably benign	Het
Chd8	T	A	14: 52,215,241	S1274C	probably damaging	Het
Chuk	A	T	19: 44,107,343	M17K	possibly damaging	Het
Col14a1	C	T	15: 55,446,181		probably benign	Het
Col20a1	G	A	2: 181,013,163		probably null	Het
Cped1	A	G	6: 22,143,964	I570V	probably benign	Het
Cul9	C	G	17: 46,522,175	A1326P	probably damaging	Het
Ddx27	A	C	2: 167,033,771	Q674P	probably damaging	Het
Dennd6a	T	A	14: 26,612,003	F131L	probably damaging	Het
Dhx38	G	A	8: 109,556,869		probably benign	Het
Dido1	G	T	2: 180,659,585	N2175K	unknown	Het
Dmxl1	T	A	18: 49,889,558	Y1654*	probably null	Het
Dock7	T	A	4: 98,959,101	H1658L	probably damaging	Het
Dync2h1	T	A	9: 7,122,772	E2061D	probably damaging	Het
Dync2h1	T	C	9: 7,162,925	I555V	probably benign	Het
Eif2ak2	T	C	17: 78,863,963	E337G	possibly damaging	Het
Fabp12	T	A	3: 10,250,149	D46V	probably benign	Het
Fech	C	T	18: 64,478,727	E79K	probably damaging	Het
Flnc	A	T	6: 29,444,363	I693F	probably damaging	Het
Foxp2	G	A	6: 15,324,644	C97Y	possibly damaging	Het
Grin2b	A	G	6: 135,733,896	M884T	probably benign	Het
Gtf2ird1	T	C	5: 134,417,093	D28G	probably damaging	Het
Gtf3c4	C	A	2: 28,833,894	G468W	possibly damaging	Het
Ift172	A	T	5: 31,267,241	L201*	probably null	Het
Il1rl2	C	A	1: 40,365,214	S498R	probably damaging	Het
Ildr1	C	T	16: 36,725,541	R489W	probably damaging	Het
Itga10	G	A	3: 96,652,490	G487D	probably damaging	Het
Klk8	A	G	7: 43,799,216	N128D	probably benign	Het
Lgr6	G	A	1: 135,075,275	T79M	probably damaging	Het
Med6	T	C	12: 81,573,877	T232A	probably benign	Het
Mgat4e	A	G	1: 134,541,322	L328P	probably damaging	Het
Mttp	A	G	3: 138,118,402	Y138H	probably damaging	Het
Ngef	T	C	1: 87,545,968	R31G	probably benign	Het
Nipsnap2	C	A	5: 129,753,223		probably null	Het
Nlgn2	G	T	11: 69,828,441	N194K	probably damaging	Het
Olfr1026	A	G	2: 85,923,743	I158M	probably benign	Het
Olfr1245	A	T	2: 89,574,961	M255K	possibly damaging	Het
Olfr1450	G	A	19: 12,954,332	V248I	possibly damaging	Het
Olfr357	G	A	2: 36,997,652	V281M	possibly damaging	Het
Olfr894	A	G	9: 38,219,432	Y203C	possibly damaging	Het
Pcca	T	A	14: 122,813,222	M101K	possibly damaging	Het
Plekha6	A	G	1: 133,284,970	T671A	possibly damaging	Het
Prex2	G	A	1: 11,162,312	V868M	probably damaging	Het
Prkcq	G	A	2: 11,279,521	V501I	probably benign	Het
Prom1	T	A	5: 44,011,253		probably benign	Het
Ptprd	A	G	4: 76,133,161	V41A	probably damaging	Het
Rab39	C	T	9: 53,686,398	G189E	possibly damaging	Het
Ret	T	C	6: 118,180,382	K236E	possibly damaging	Het
Rfx6	G	A	10: 51,720,057		probably null	Het
Rnf213	A	G	11: 119,461,918	T3916A	probably damaging	Het
Rpn1	A	G	6: 88,095,683	N336S	probably damaging	Het
Sag	G	A	1: 87,805,315	A2T	probably damaging	Het
Sco2	T	C	15: 89,371,860	Y197C	probably damaging	Het
Sec23b	T	C	2: 144,566,944	I183T	possibly damaging	Het
Sec24b	C	T	3: 129,987,728	V1166M	probably damaging	Het
Slc27a5	A	T	7: 12,993,412	F361Y	probably damaging	Het
Spaca9	A	G	2: 28,696,001	L17P	probably damaging	Het
Sqor	T	C	2: 122,804,107		probably null	Het
Stx18	A	G	5: 38,135,244	H230R	probably damaging	Het
Tas2r130	A	T	6: 131,630,769	I21N	probably damaging	Het
Tcaf3	A	G	6: 42,593,724	S365P	possibly damaging	Het
Tinagl1	G	A	4: 130,166,972	H351Y	probably damaging	Het
Tmc2	T	C	2: 130,232,385	Y333H	probably damaging	Het
Trp53bp2	A	T	1: 182,442,819	T395S	probably damaging	Het
Tsc22d1	T	C	14: 76,418,333	S751P	probably damaging	Het
Ttc30a1	A	G	2: 75,980,935	V268A	probably benign	Het
Ttn	A	G	2: 76,827,024		probably benign	Het
Ugdh	T	C	5: 65,416,925	Y425C	probably damaging	Het
Vmn1r115	G	A	7: 20,844,169	L273F	probably null	Het
Vmn2r109	A	T	17: 20,541,186	C636*	probably null	Het
Vmn2r59	A	C	7: 42,043,779	Y466D	probably damaging	Het
Zic5	C	T	14: 122,464,830	G163D	unknown	Het

Other mutations in Adam17

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00555:Adam17	APN	12	21328109	missense	probably damaging	1.00
IGL01340:Adam17	APN	12	21330057	nonsense	probably null
IGL01973:Adam17	APN	12	21349943	missense	probably damaging	1.00
IGL02223:Adam17	APN	12	21361705	missense	possibly damaging	0.92
IGL03153:Adam17	APN	12	21345697	missense	probably damaging	1.00
Steinway	UTSW	12	21353948	missense	probably damaging	1.00
wavedx	UTSW	12	21340750	missense	probably damaging	1.00
R0014:Adam17	UTSW	12	21336644	missense	probably benign	0.36
R0080:Adam17	UTSW	12	21329048	splice site	probably benign
R0082:Adam17	UTSW	12	21329048	splice site	probably benign
R0324:Adam17	UTSW	12	21349938	missense	probably benign	0.00
R0511:Adam17	UTSW	12	21340458	splice site	probably benign
R0745:Adam17	UTSW	12	21332221	splice site	probably benign
R1314:Adam17	UTSW	12	21329071	missense	probably damaging	1.00
R1547:Adam17	UTSW	12	21353957	missense	probably damaging	1.00
R1594:Adam17	UTSW	12	21340470	critical splice donor site	probably null
R1607:Adam17	UTSW	12	21334138	splice site	probably null
R1812:Adam17	UTSW	12	21361767	missense	probably damaging	0.97
R3408:Adam17	UTSW	12	21329118	missense	probably damaging	1.00
R3735:Adam17	UTSW	12	21325412	missense	probably benign	0.05
R3886:Adam17	UTSW	12	21325587	missense	probably damaging	1.00
R3888:Adam17	UTSW	12	21325587	missense	probably damaging	1.00
R4062:Adam17	UTSW	12	21325457	missense	probably damaging	1.00
R4415:Adam17	UTSW	12	21345701	missense	possibly damaging	0.90
R4563:Adam17	UTSW	12	21332088	missense	probably damaging	1.00
R4658:Adam17	UTSW	12	21332160	missense	probably damaging	1.00
R4763:Adam17	UTSW	12	21334015	missense	probably benign
R4793:Adam17	UTSW	12	21347395	missense	probably benign
R5101:Adam17	UTSW	12	21373405	missense	possibly damaging	0.85
R5120:Adam17	UTSW	12	21343019	intron	probably benign
R5514:Adam17	UTSW	12	21340519	missense	probably damaging	0.98
R5592:Adam17	UTSW	12	21334137	missense	probably damaging	1.00
R5874:Adam17	UTSW	12	21329086	missense	possibly damaging	0.76
R6110:Adam17	UTSW	12	21353948	missense	probably damaging	1.00
R6451:Adam17	UTSW	12	21342882	missense	probably benign	0.00
R6930:Adam17	UTSW	12	21353948	missense	probably damaging	1.00
R6970:Adam17	UTSW	12	21345668	missense	probably benign	0.06
R7213:Adam17	UTSW	12	21336678	nonsense	probably null
R7302:Adam17	UTSW	12	21355693	intron	probably benign
R7361:Adam17	UTSW	12	21325601	missense	probably damaging	0.98
R7667:Adam17	UTSW	12	21333952	critical splice donor site	probably null
R7799:Adam17	UTSW	12	21340492	missense	probably damaging	1.00
R8762:Adam17	UTSW	12	21351594	missense	probably benign	0.03
R8958:Adam17	UTSW	12	21349933	missense	possibly damaging	0.61
R9108:Adam17	UTSW	12	21330131	missense	probably benign
R9163:Adam17	UTSW	12	21351587	missense	probably benign	0.00
R9295:Adam17	UTSW	12	21349937	missense	probably benign	0.02
R9345:Adam17	UTSW	12	21328055	missense	probably damaging	1.00
R9444:Adam17	UTSW	12	21325535	missense	probably benign	0.28
R9522:Adam17	UTSW	12	21345692	missense	probably damaging	1.00
R9582:Adam17	UTSW	12	21336664	missense	probably benign	0.14
X0063:Adam17	UTSW	12	21332585	missense	probably benign	0.17
Z1176:Adam17	UTSW	12	21361737	missense	possibly damaging	0.94

Predicted Primers

PCR Primer
(F):5'- CTGTAACAAAACTGTATTTTCAGACCA -3'
(R):5'- AGAAACTGTAAGATTAAACAAGCACT -3'

Sequencing Primer
(F):5'- GTTCGATTCCCAGTAACCACATGATG -3'
(R):5'- CCAAGAACAAAGAATGTTGTG -3'

Posted On

2014-08-25