Mutagenetix > Incidental Mutation

Incidental Mutation 'R9356:Myo7a'

708418

Institutional Source

Beutler Lab

Gene Symbol

Myo7a

Ensembl Gene

ENSMUSG00000030761

Gene Name

myosin VIIA

Synonyms

nmf371, USH1B, polka, Hdb, Myo7

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R9356 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

97700267-97768731 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 97725873 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Leucine at position 1060 (M1060L)

Ref Sequence

ENSEMBL: ENSMUSP00000082046 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000084979] [ENSMUST00000107122] [ENSMUST00000107127] [ENSMUST00000107128] [ENSMUST00000205746]

AlphaFold

P97479

Predicted Effect

probably benign
Transcript: ENSMUST00000084979
AA Change: M1060L

PolyPhen 2 Score 0.112 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000082046
Gene: ENSMUSG00000030761
AA Change: M1060L

Domain	Start	End	E-Value	Type
MYSc	48	731	N/A	SMART
IQ	732	754	2.99e0	SMART
IQ	755	777	8.77e-7	SMART
IQ	801	823	8e0	SMART
IQ	824	846	8.7e0	SMART
low complexity region	854	889	N/A	INTRINSIC
low complexity region	893	916	N/A	INTRINSIC
low complexity region	972	985	N/A	INTRINSIC
MyTH4	1006	1242	1.4e-71	SMART
B41	1243	1458	8.82e-42	SMART
SH3	1557	1622	4.93e-7	SMART
MyTH4	1698	1847	3.95e-57	SMART
B41	1849	2066	8.27e-56	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000107122
AA Change: M1066L

PolyPhen 2 Score 0.528 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000102739
Gene: ENSMUSG00000030761
AA Change: M1066L

Domain	Start	End	E-Value	Type
MYSc	48	737	N/A	SMART
IQ	738	760	2.99e0	SMART
IQ	761	783	8.77e-7	SMART
IQ	807	829	8e0	SMART
IQ	830	852	8.7e0	SMART
low complexity region	860	895	N/A	INTRINSIC
low complexity region	899	922	N/A	INTRINSIC
low complexity region	978	991	N/A	INTRINSIC
MyTH4	1012	1248	1.4e-71	SMART
B41	1249	1464	8.82e-42	SMART
SH3	1563	1628	4.93e-7	SMART
MyTH4	1704	1853	3.95e-57	SMART
B41	1855	2072	8.27e-56	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000107127
AA Change: M1071L

PolyPhen 2 Score 0.946 (Sensitivity: 0.80; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000102744
Gene: ENSMUSG00000030761
AA Change: M1071L

Domain	Start	End	E-Value	Type
MYSc	59	742	N/A	SMART
IQ	743	765	2.99e0	SMART
IQ	766	788	8.77e-7	SMART
IQ	812	834	8e0	SMART
IQ	835	857	8.7e0	SMART
low complexity region	865	900	N/A	INTRINSIC
low complexity region	904	927	N/A	INTRINSIC
low complexity region	983	996	N/A	INTRINSIC
MyTH4	1017	1253	1.4e-71	SMART
B41	1254	1469	8.82e-42	SMART
SH3	1568	1633	4.93e-7	SMART
MyTH4	1709	1858	3.95e-57	SMART
B41	1860	2077	8.27e-56	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000107128
AA Change: M1071L

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000102745
Gene: ENSMUSG00000030761
AA Change: M1071L

Domain	Start	End	E-Value	Type
MYSc	59	742	N/A	SMART
IQ	743	765	2.99e0	SMART
IQ	766	788	8.77e-7	SMART
IQ	812	834	8e0	SMART
IQ	835	857	8.7e0	SMART
low complexity region	865	900	N/A	INTRINSIC
low complexity region	904	927	N/A	INTRINSIC
low complexity region	983	996	N/A	INTRINSIC
MyTH4	1017	1253	1.4e-71	SMART
B41	1254	1469	8.82e-42	SMART
SH3	1606	1671	4.93e-7	SMART
MyTH4	1747	1896	3.95e-57	SMART
B41	1898	2115	8.27e-56	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000205746
AA Change: M1060L

PolyPhen 2 Score 0.910 (Sensitivity: 0.81; Specificity: 0.94)

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
PHENOTYPE: A number of spontaneous and ENU-induced mutations cause head-shaking, circling and deafness, often associated with cochlear hair cell degeneration and stereocilia anomalies. Defects in retinal pigment epithelial cells, male infertility, and light-inducedphotoreceptor damage have also been observed. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca13	G	A	11: 9,206,305 (GRCm39)	V202M	probably benign	Het
Ago3	A	T	4: 126,264,144 (GRCm39)	I354N	probably damaging	Het
Ankrd50	A	T	3: 38,510,236 (GRCm39)	D710E	probably damaging	Het
Apba2	A	T	7: 64,345,421 (GRCm39)	N204Y	probably damaging	Het
Arrdc4	A	G	7: 68,394,627 (GRCm39)	V139A	possibly damaging	Het
Baz1b	A	G	5: 135,239,653 (GRCm39)	E251G	probably benign	Het
Calcr	T	C	6: 3,687,408 (GRCm39)	D530G	probably benign	Het
Chrna7	A	T	7: 62,757,437 (GRCm39)	V154E	probably damaging	Het
Cldn15	T	C	5: 136,996,968 (GRCm39)	V3A	probably benign	Het
Csmd1	A	T	8: 16,252,069 (GRCm39)	L929Q	probably damaging	Het
Ctss	A	C	3: 95,454,120 (GRCm39)	H224P	possibly damaging	Het
Cyp4a12a	C	A	4: 115,185,915 (GRCm39)	H408N	probably benign	Het
Gm10549	C	T	18: 33,597,375 (GRCm39)	P54S	unknown	Het
Gpr162	T	C	6: 124,838,297 (GRCm39)	M118V	possibly damaging	Het
Ifnar1	C	T	16: 91,292,367 (GRCm39)	P207L	probably benign	Het
Igfn1	A	T	1: 135,899,825 (GRCm39)	C495*	probably null	Het
Ints9	T	C	14: 65,269,770 (GRCm39)	S487P	probably benign	Het
Jmjd4	T	A	11: 59,345,761 (GRCm39)	D280E	probably benign	Het
Krtap1-4	G	A	11: 99,474,169 (GRCm39)	Q96*	probably null	Het
Ksr2	T	A	5: 117,827,706 (GRCm39)	I495N	probably benign	Het
Lama2	T	A	10: 27,088,186 (GRCm39)	N864Y	probably damaging	Het
Lce1f	TCCACAGCAGCCACTGCTGCCACCACTGCTGCCACAGCAGCCACTGCTGCCACCACTGCTGCCACAGCAGCCACTGCTGCCACCACTGCT	TCCACAGCAGCCACTGCTGCCACCACTGCTGCCACAGCAGCCACTGCTGCCACCACTGCT	3: 92,626,272 (GRCm39)		probably benign	Het
Lig4	A	G	8: 10,022,538 (GRCm39)	V414A	possibly damaging	Het
Lman2l	A	G	1: 36,467,415 (GRCm39)	F211S	probably damaging	Het
Lmtk3	A	G	7: 45,443,312 (GRCm39)	E665G	probably damaging	Het
Mdm4	G	A	1: 132,938,837 (GRCm39)	L86F	probably damaging	Het
Mfsd10	C	A	5: 34,794,048 (GRCm39)	E22*	probably null	Het
Mindy1	C	T	3: 95,202,590 (GRCm39)	L394F	probably benign	Het
Mroh4	T	C	15: 74,482,760 (GRCm39)	M735V	probably benign	Het
Myo7b	C	A	18: 32,110,096 (GRCm39)	S1122I	probably damaging	Het
Nudt17	T	A	3: 96,613,688 (GRCm39)	R313S	probably damaging	Het
Or52n5	A	G	7: 104,588,373 (GRCm39)	I213M	probably benign	Het
Or5w15	T	A	2: 87,568,089 (GRCm39)	Q193L	probably benign	Het
Or6c65	T	G	10: 129,604,035 (GRCm39)	I223M	possibly damaging	Het
Or8h7	T	A	2: 86,720,605 (GRCm39)	M305L	probably benign	Het
Otogl	T	C	10: 107,617,890 (GRCm39)	Y1741C	probably damaging	Het
Pja2	A	G	17: 64,618,204 (GRCm39)	V65A	probably damaging	Het
Primpol	A	G	8: 47,043,318 (GRCm39)	V325A	probably benign	Het
Prss36	T	C	7: 127,545,697 (GRCm39)		probably benign	Het
Ptpn20	T	G	14: 33,352,865 (GRCm39)	Y201*	probably null	Het
Rundc3a	T	C	11: 102,292,890 (GRCm39)	S428P	probably damaging	Het
Rxra	T	A	2: 27,649,675 (GRCm39)	L460Q	probably damaging	Het
Sdsl	C	T	5: 120,597,948 (GRCm39)	V182M	probably damaging	Het
Slc14a2	A	C	18: 78,227,823 (GRCm39)	I226S	probably null	Het
Spam1	T	A	6: 24,800,565 (GRCm39)	C435S	probably damaging	Het
Spata31h1	T	C	10: 82,125,157 (GRCm39)	K2618E	possibly damaging	Het
Stbd1	A	G	5: 92,753,277 (GRCm39)	T256A	possibly damaging	Het
Ttc39c	T	A	18: 12,853,102 (GRCm39)		probably null	Het
Uba3	T	C	6: 97,161,811 (GRCm39)	D440G	probably benign	Het
Ythdf1	A	C	2: 180,553,998 (GRCm39)	S72R	probably benign	Het
Zfp770	T	C	2: 114,026,917 (GRCm39)	E384G	possibly damaging	Het
Zfp979	G	T	4: 147,698,358 (GRCm39)	T117K	probably damaging	Het

Other mutations in Myo7a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00465:Myo7a	APN	7	97,751,833 (GRCm39)	missense	probably damaging	1.00
IGL00785:Myo7a	APN	7	97,703,555 (GRCm39)	missense	probably damaging	0.99
IGL00840:Myo7a	APN	7	97,700,866 (GRCm39)	missense	probably benign	0.25
IGL01362:Myo7a	APN	7	97,746,909 (GRCm39)	missense	probably damaging	1.00
IGL01484:Myo7a	APN	7	97,734,629 (GRCm39)	missense	probably damaging	1.00
IGL01673:Myo7a	APN	7	97,703,915 (GRCm39)	missense	probably benign	0.00
IGL01933:Myo7a	APN	7	97,732,349 (GRCm39)	missense	probably damaging	1.00
IGL01943:Myo7a	APN	7	97,714,854 (GRCm39)	missense	possibly damaging	0.96
IGL02188:Myo7a	APN	7	97,740,234 (GRCm39)	missense	probably damaging	0.96
IGL02304:Myo7a	APN	7	97,726,943 (GRCm39)	missense	possibly damaging	0.89
IGL02305:Myo7a	APN	7	97,700,836 (GRCm39)	makesense	probably null
IGL02331:Myo7a	APN	7	97,702,389 (GRCm39)	missense	possibly damaging	0.95
IGL02386:Myo7a	APN	7	97,724,319 (GRCm39)	missense	probably damaging	0.99
IGL02389:Myo7a	APN	7	97,756,198 (GRCm39)	critical splice donor site	probably null
IGL02832:Myo7a	APN	7	97,740,227 (GRCm39)	critical splice donor site	probably null
IGL02839:Myo7a	APN	7	97,740,329 (GRCm39)	missense	probably damaging	1.00
IGL03193:Myo7a	APN	7	97,740,264 (GRCm39)	missense	probably damaging	1.00
IGL03237:Myo7a	APN	7	97,751,800 (GRCm39)	missense	probably damaging	1.00
IGL03384:Myo7a	APN	7	97,742,800 (GRCm39)	missense	probably damaging	1.00
coward	UTSW	7	97,734,673 (GRCm39)	missense	probably damaging	1.00
H8786:Myo7a	UTSW	7	97,744,985 (GRCm39)	missense	possibly damaging	0.61
IGL03046:Myo7a	UTSW	7	97,728,534 (GRCm39)	missense	probably damaging	1.00
IGL03134:Myo7a	UTSW	7	97,705,974 (GRCm39)	missense	probably damaging	0.96
PIT4696001:Myo7a	UTSW	7	97,712,806 (GRCm39)	missense	probably benign	0.00
R0054:Myo7a	UTSW	7	97,714,905 (GRCm39)	missense	probably damaging	1.00
R0054:Myo7a	UTSW	7	97,714,905 (GRCm39)	missense	probably damaging	1.00
R0071:Myo7a	UTSW	7	97,706,037 (GRCm39)	missense	probably damaging	0.98
R0071:Myo7a	UTSW	7	97,706,037 (GRCm39)	missense	probably damaging	0.98
R0267:Myo7a	UTSW	7	97,703,831 (GRCm39)	missense	probably benign	0.08
R0408:Myo7a	UTSW	7	97,705,988 (GRCm39)	missense	probably damaging	1.00
R0411:Myo7a	UTSW	7	97,721,144 (GRCm39)	missense	probably benign	0.00
R0540:Myo7a	UTSW	7	97,721,153 (GRCm39)	missense	probably damaging	1.00
R0607:Myo7a	UTSW	7	97,721,153 (GRCm39)	missense	probably damaging	1.00
R0629:Myo7a	UTSW	7	97,734,673 (GRCm39)	missense	probably damaging	1.00
R0632:Myo7a	UTSW	7	97,761,357 (GRCm39)	intron	probably benign
R0659:Myo7a	UTSW	7	97,703,545 (GRCm39)	splice site	probably benign
R0735:Myo7a	UTSW	7	97,730,387 (GRCm39)	splice site	probably benign
R0924:Myo7a	UTSW	7	97,747,463 (GRCm39)	missense	probably damaging	0.99
R0930:Myo7a	UTSW	7	97,747,463 (GRCm39)	missense	probably damaging	0.99
R1018:Myo7a	UTSW	7	97,756,212 (GRCm39)	missense	probably damaging	1.00
R1196:Myo7a	UTSW	7	97,746,880 (GRCm39)	missense	possibly damaging	0.87
R1331:Myo7a	UTSW	7	97,756,215 (GRCm39)	missense	probably benign	0.00
R1487:Myo7a	UTSW	7	97,703,017 (GRCm39)	critical splice donor site	probably null
R1676:Myo7a	UTSW	7	97,748,679 (GRCm39)	critical splice donor site	probably null
R1695:Myo7a	UTSW	7	97,741,703 (GRCm39)	missense	possibly damaging	0.94
R1770:Myo7a	UTSW	7	97,761,813 (GRCm39)	intron	probably benign
R1781:Myo7a	UTSW	7	97,722,331 (GRCm39)	missense	probably damaging	1.00
R1789:Myo7a	UTSW	7	97,756,302 (GRCm39)	missense	probably damaging	0.99
R1827:Myo7a	UTSW	7	97,725,938 (GRCm39)	missense	probably damaging	0.99
R1864:Myo7a	UTSW	7	97,701,463 (GRCm39)	missense	probably damaging	1.00
R1955:Myo7a	UTSW	7	97,704,128 (GRCm39)	missense	probably damaging	1.00
R2011:Myo7a	UTSW	7	97,703,915 (GRCm39)	missense	possibly damaging	0.69
R2229:Myo7a	UTSW	7	97,704,117 (GRCm39)	missense	probably benign	0.12
R2259:Myo7a	UTSW	7	97,718,706 (GRCm39)	missense	probably damaging	1.00
R2443:Myo7a	UTSW	7	97,744,976 (GRCm39)	missense	probably benign	0.07
R2898:Myo7a	UTSW	7	97,746,413 (GRCm39)	missense	probably damaging	1.00
R2898:Myo7a	UTSW	7	97,703,631 (GRCm39)	nonsense	probably null
R3158:Myo7a	UTSW	7	97,701,499 (GRCm39)	missense	probably damaging	1.00
R3408:Myo7a	UTSW	7	97,730,294 (GRCm39)	missense	probably benign	0.00
R4222:Myo7a	UTSW	7	97,722,436 (GRCm39)	missense	possibly damaging	0.93
R4255:Myo7a	UTSW	7	97,721,171 (GRCm39)	missense	probably damaging	0.96
R4374:Myo7a	UTSW	7	97,751,881 (GRCm39)	missense	probably damaging	1.00
R4429:Myo7a	UTSW	7	97,702,395 (GRCm39)	missense	probably damaging	0.99
R4445:Myo7a	UTSW	7	97,715,611 (GRCm39)	missense	probably damaging	1.00
R4579:Myo7a	UTSW	7	97,722,400 (GRCm39)	missense	probably damaging	1.00
R4659:Myo7a	UTSW	7	97,734,673 (GRCm39)	missense	probably damaging	1.00
R5073:Myo7a	UTSW	7	97,722,425 (GRCm39)	nonsense	probably null
R5138:Myo7a	UTSW	7	97,732,806 (GRCm39)	missense	probably damaging	1.00
R5566:Myo7a	UTSW	7	97,714,023 (GRCm39)	missense	possibly damaging	0.93
R5580:Myo7a	UTSW	7	97,722,367 (GRCm39)	missense	probably damaging	1.00
R6079:Myo7a	UTSW	7	97,714,997 (GRCm39)	nonsense	probably null
R6138:Myo7a	UTSW	7	97,714,997 (GRCm39)	nonsense	probably null
R6451:Myo7a	UTSW	7	97,722,374 (GRCm39)	missense	probably benign	0.01
R6452:Myo7a	UTSW	7	97,722,374 (GRCm39)	missense	probably benign	0.01
R6453:Myo7a	UTSW	7	97,722,374 (GRCm39)	missense	probably benign	0.01
R6454:Myo7a	UTSW	7	97,722,374 (GRCm39)	missense	probably benign	0.01
R6455:Myo7a	UTSW	7	97,722,374 (GRCm39)	missense	probably benign	0.01
R6465:Myo7a	UTSW	7	97,711,887 (GRCm39)	missense	possibly damaging	0.95
R6653:Myo7a	UTSW	7	97,703,710 (GRCm39)	missense	probably damaging	0.96
R6709:Myo7a	UTSW	7	97,703,906 (GRCm39)	missense	probably damaging	1.00
R6917:Myo7a	UTSW	7	97,744,970 (GRCm39)	missense	possibly damaging	0.58
R7313:Myo7a	UTSW	7	97,713,402 (GRCm39)	missense	probably damaging	0.99
R7334:Myo7a	UTSW	7	97,728,573 (GRCm39)	missense	probably benign
R7356:Myo7a	UTSW	7	97,751,890 (GRCm39)	missense	probably benign	0.01
R7393:Myo7a	UTSW	7	97,712,906 (GRCm39)	missense	possibly damaging	0.91
R7422:Myo7a	UTSW	7	97,700,833 (GRCm39)	splice site	probably null
R7472:Myo7a	UTSW	7	97,714,000 (GRCm39)	missense	probably damaging	1.00
R7483:Myo7a	UTSW	7	97,712,881 (GRCm39)	missense	probably benign	0.07
R7526:Myo7a	UTSW	7	97,734,655 (GRCm39)	missense	possibly damaging	0.49
R7948:Myo7a	UTSW	7	97,724,236 (GRCm39)	missense	probably damaging	1.00
R8069:Myo7a	UTSW	7	97,732,833 (GRCm39)	nonsense	probably null
R8115:Myo7a	UTSW	7	97,715,653 (GRCm39)	missense	probably damaging	0.98
R8150:Myo7a	UTSW	7	97,712,846 (GRCm39)	missense	probably benign	0.19
R8265:Myo7a	UTSW	7	97,734,604 (GRCm39)	missense	probably benign	0.00
R8289:Myo7a	UTSW	7	97,726,376 (GRCm39)	missense	probably benign
R8298:Myo7a	UTSW	7	97,747,541 (GRCm39)	missense	probably damaging	1.00
R8518:Myo7a	UTSW	7	97,740,270 (GRCm39)	missense	possibly damaging	0.58
R8539:Myo7a	UTSW	7	97,721,668 (GRCm39)	missense	probably damaging	0.99
R8557:Myo7a	UTSW	7	97,703,081 (GRCm39)	missense	probably benign	0.08
R8685:Myo7a	UTSW	7	97,746,334 (GRCm39)	missense	probably benign	0.03
R8902:Myo7a	UTSW	7	97,741,820 (GRCm39)	missense	probably damaging	1.00
R9034:Myo7a	UTSW	7	97,728,465 (GRCm39)	missense	probably benign	0.40
R9090:Myo7a	UTSW	7	97,740,281 (GRCm39)	missense	probably benign	0.04
R9172:Myo7a	UTSW	7	97,732,369 (GRCm39)	missense	probably benign
R9271:Myo7a	UTSW	7	97,740,281 (GRCm39)	missense	probably benign	0.04
R9334:Myo7a	UTSW	7	97,716,369 (GRCm39)	missense	probably damaging	1.00
R9444:Myo7a	UTSW	7	97,742,698 (GRCm39)	missense	possibly damaging	0.84
R9459:Myo7a	UTSW	7	97,722,380 (GRCm39)	missense	possibly damaging	0.65
R9513:Myo7a	UTSW	7	97,746,818 (GRCm39)	critical splice donor site	probably null
R9517:Myo7a	UTSW	7	97,721,166 (GRCm39)	missense	probably damaging	1.00
R9629:Myo7a	UTSW	7	97,712,937 (GRCm39)	missense	probably benign	0.03
R9662:Myo7a	UTSW	7	97,747,499 (GRCm39)	missense	possibly damaging	0.55
R9709:Myo7a	UTSW	7	97,743,536 (GRCm39)	missense	possibly damaging	0.79
RF005:Myo7a	UTSW	7	97,742,824 (GRCm39)	missense	probably benign	0.42
U15987:Myo7a	UTSW	7	97,714,997 (GRCm39)	nonsense	probably null
X0028:Myo7a	UTSW	7	97,714,932 (GRCm39)	missense	probably damaging	1.00
X0058:Myo7a	UTSW	7	97,711,855 (GRCm39)	missense	probably benign	0.02
Z1176:Myo7a	UTSW	7	97,744,934 (GRCm39)	missense	probably damaging	0.98
Z1177:Myo7a	UTSW	7	97,734,730 (GRCm39)	critical splice acceptor site	probably null
Z1177:Myo7a	UTSW	7	97,701,433 (GRCm39)	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- ATGGCTCGCACATTATTCCC -3'
(R):5'- ACCTAGGGTCAGACCACATC -3'

Sequencing Primer
(F):5'- ATTATTCCCACGAGTAGACAGAG -3'
(R):5'- ACATCTGCAGGTGGCTGTCTC -3'

Posted On

2022-04-18