Mutagenetix > Incidental Mutation

Incidental Mutation 'R6805:Col18a1'

533541

Institutional Source

Beutler Lab

Gene Symbol

Col18a1

Ensembl Gene

ENSMUSG00000001435

Gene Name

collagen, type XVIII, alpha 1

Synonyms

endostatin

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6805 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

77052178-77166548 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 77054239 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 1429 (L1429P)

Ref Sequence

ENSEMBL: ENSMUSP00000101049 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000072755] [ENSMUST00000081654] [ENSMUST00000105409] [ENSMUST00000105410] [ENSMUST00000144234]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000072755
AA Change: L1676P

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

SMART Domains

Protein: ENSMUSP00000072538
Gene: ENSMUSG00000001435
AA Change: L1676P

Domain	Start	End	E-Value	Type
Pfam:DUF959	16	218	6.8e-104	PFAM
low complexity region	295	307	N/A	INTRINSIC
FRI	369	484	4.03e-47	SMART
TSPN	492	680	4.25e-72	SMART
LamG	541	679	2.17e-2	SMART
low complexity region	699	715	N/A	INTRINSIC
low complexity region	719	734	N/A	INTRINSIC
low complexity region	739	751	N/A	INTRINSIC
Pfam:Collagen	820	881	5.5e-11	PFAM
low complexity region	921	942	N/A	INTRINSIC
Pfam:Collagen	951	1008	6.1e-10	PFAM
Pfam:Collagen	988	1053	1.4e-8	PFAM
Pfam:Collagen	1060	1117	7.3e-10	PFAM
low complexity region	1132	1147	N/A	INTRINSIC
low complexity region	1166	1181	N/A	INTRINSIC
low complexity region	1186	1202	N/A	INTRINSIC
Pfam:Collagen	1207	1267	8.2e-10	PFAM
low complexity region	1275	1288	N/A	INTRINSIC
low complexity region	1301	1319	N/A	INTRINSIC
low complexity region	1358	1393	N/A	INTRINSIC
low complexity region	1397	1414	N/A	INTRINSIC
low complexity region	1417	1433	N/A	INTRINSIC
low complexity region	1441	1454	N/A	INTRINSIC
Pfam:Endostatin	1461	1769	4.4e-116	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000081654
AA Change: L1217P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000080358
Gene: ENSMUSG00000001435
AA Change: L1217P

Domain	Start	End	E-Value	Type
signal peptide	1	25	N/A	INTRINSIC
TSPN	33	221	4.25e-72	SMART
LamG	82	220	2.17e-2	SMART
low complexity region	240	256	N/A	INTRINSIC
low complexity region	260	275	N/A	INTRINSIC
low complexity region	280	292	N/A	INTRINSIC
Pfam:Collagen	359	422	1.6e-10	PFAM
low complexity region	462	483	N/A	INTRINSIC
Pfam:Collagen	492	549	1.6e-9	PFAM
Pfam:Collagen	529	594	3.3e-8	PFAM
Pfam:Collagen	601	658	1.9e-9	PFAM
Pfam:Collagen	631	689	4e-8	PFAM
Pfam:Collagen	701	752	1.7e-7	PFAM
Pfam:Collagen	748	808	2.2e-9	PFAM
low complexity region	816	829	N/A	INTRINSIC
low complexity region	842	860	N/A	INTRINSIC
low complexity region	899	934	N/A	INTRINSIC
low complexity region	938	955	N/A	INTRINSIC
low complexity region	958	974	N/A	INTRINSIC
low complexity region	982	995	N/A	INTRINSIC
Pfam:Endostatin	999	1315	8.2e-151	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000105409
AA Change: L1429P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000101049
Gene: ENSMUSG00000001435
AA Change: L1429P

Domain	Start	End	E-Value	Type
Pfam:DUF959	16	219	3.6e-100	PFAM
TSPN	245	433	4.25e-72	SMART
LamG	294	432	2.17e-2	SMART
low complexity region	452	468	N/A	INTRINSIC
low complexity region	472	487	N/A	INTRINSIC
low complexity region	492	504	N/A	INTRINSIC
low complexity region	542	613	N/A	INTRINSIC
low complexity region	630	648	N/A	INTRINSIC
low complexity region	674	695	N/A	INTRINSIC
Pfam:Collagen	700	761	5.4e-9	PFAM
Pfam:Collagen	741	806	4e-8	PFAM
Pfam:Collagen	813	874	2.1e-10	PFAM
Pfam:Collagen	846	901	1.2e-7	PFAM
Pfam:Collagen	913	964	2.1e-7	PFAM
Pfam:Collagen	960	1020	2.6e-9	PFAM
low complexity region	1028	1041	N/A	INTRINSIC
low complexity region	1054	1072	N/A	INTRINSIC
low complexity region	1111	1146	N/A	INTRINSIC
low complexity region	1150	1167	N/A	INTRINSIC
low complexity region	1170	1186	N/A	INTRINSIC
low complexity region	1194	1207	N/A	INTRINSIC
Pfam:Endostatin	1211	1527	1.1e-150	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105410

SMART Domains

Protein: ENSMUSP00000101050
Gene: ENSMUSG00000001436

Domain	Start	End	E-Value	Type
Pfam:Folate_carrier	23	427	3e-167	PFAM
Pfam:MFS_1	66	406	2.6e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000131031

SMART Domains

Protein: ENSMUSP00000114884
Gene: ENSMUSG00000001436

Domain	Start	End	E-Value	Type
Pfam:Folate_carrier	1	112	1.3e-45	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000144234

SMART Domains

Protein: ENSMUSP00000116784
Gene: ENSMUSG00000001436

Domain	Start	End	E-Value	Type
Pfam:Folate_carrier	23	427	3e-167	PFAM
Pfam:MFS_1	66	406	2.6e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000218407

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.8%
20x: 97.1%

Validation Efficiency

98% (62/63)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit defects in hyaloid vessel regression, attenuated visual function, abnormal electroretinograms, broad proximal tubule basement membrane, podocyte effacement, and softened glomeruli. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410089E03Rik	T	C	15: 8,244,306	V2591A	probably benign	Het
4930407I10Rik	A	G	15: 82,062,543	T214A	possibly damaging	Het
A930009A15Rik	G	T	10: 115,579,905		probably benign	Het
Aadac	A	C	3: 60,037,336	D143A	probably benign	Het
Acot10	T	G	15: 20,665,366	T430P	probably benign	Het
Adgrb3	T	C	1: 25,826,172	T197A	possibly damaging	Het
B230118H07Rik	T	C	2: 101,566,459	K192E	probably benign	Het
Bbs1	A	G	19: 4,900,615	I200T	probably damaging	Het
C1ra	G	A	6: 124,517,725	E316K	probably benign	Het
Cadps	G	A	14: 12,467,103	A943V	probably damaging	Het
Cc2d2a	A	G	5: 43,681,331	E48G	probably damaging	Het
Clca1	A	T	3: 145,018,667	C211S	probably damaging	Het
Cul2	T	G	18: 3,421,263	Y196D	probably damaging	Het
D630023F18Rik	T	C	1: 65,117,206	S43G	probably benign	Het
Ddx39	G	A	8: 83,723,137	R427Q	probably damaging	Het
Def6	A	G	17: 28,223,717	T285A	probably damaging	Het
Defb21	T	A	2: 152,574,869	D88E	probably benign	Het
Defb6	A	G	8: 19,228,101	K63R	probably benign	Het
Dnph1	T	C	17: 46,498,744	S112P	probably damaging	Het
Dock10	T	A	1: 80,586,690	I467L	probably benign	Het
Dspp	C	A	5: 104,175,850	H286Q	probably benign	Het
Eya1	T	A	1: 14,183,277	T459S	probably benign	Het
Faf1	T	C	4: 109,861,852	L385P	probably damaging	Het
Fbxw21	C	A	9: 109,157,565	R82L	probably damaging	Het
Fryl	A	G	5: 73,065,094	V2048A	probably benign	Het
Galnt5	A	T	2: 58,035,299	D864V	possibly damaging	Het
Gata6	T	G	18: 11,054,460	S130A	possibly damaging	Het
Gbf1	G	T	19: 46,262,507	R434L	probably damaging	Het
Gga3	A	G	11: 115,585,762	F709L	probably damaging	Het
Hcar1	A	G	5: 123,879,130	V166A	probably benign	Het
Hexa	T	A	9: 59,563,937	N491K	possibly damaging	Het
Hpse2	A	T	19: 43,294,321	C164*	probably null	Het
Ifi202b	T	C	1: 173,974,989	Y93C	probably damaging	Het
Iscu	T	A	5: 113,775,243	I79N	probably damaging	Het
Jmjd7	T	A	2: 120,031,323	Y182*	probably null	Het
Jup	A	T	11: 100,383,458	D135E	probably benign	Het
Kit	T	A	5: 75,652,808	I881N	probably damaging	Het
Llgl1	T	A	11: 60,702,865	S55T	probably benign	Het
Lonp2	G	A	8: 86,709,096	M653I	probably benign	Het
Lrp8	T	C	4: 107,854,320	Y307H	probably damaging	Het
Med13	A	T	11: 86,278,796	M1914K	possibly damaging	Het
Ms4a1	A	G	19: 11,253,173		probably null	Het
Naip1	A	G	13: 100,427,341	S439P	probably benign	Het
Nrg1	T	C	8: 31,821,264	R476G	probably damaging	Het
Olfr1129	T	A	2: 87,574,918		probably null	Het
Olfr835	G	T	9: 19,035,301	M59I	probably damaging	Het
Pds5b	T	A	5: 150,805,561		probably null	Het
Phf12	G	A	11: 78,027,373	G804R	probably damaging	Het
Pou6f2	T	C	13: 18,239,489	T234A		Het
Prune2	A	T	19: 17,120,590	I1153L	probably benign	Het
Ptprc	C	T	1: 138,067,885		probably null	Het
Qpctl	T	C	7: 19,149,154	Q11R	probably benign	Het
Rfx4	A	G	10: 84,840,228	K103E	possibly damaging	Het
Srcin1	T	A	11: 97,551,980		probably null	Het
St6galnac1	G	T	11: 116,768,944	A181D	probably damaging	Het
Stk36	T	C	1: 74,622,239	V475A	probably benign	Het
Tbc1d21	T	C	9: 58,361,288	T263A	possibly damaging	Het
Tex24	A	T	8: 27,345,000	K185N	probably damaging	Het
Tnxb	T	A	17: 34,698,153	V2174E	possibly damaging	Het
Tollip	A	G	7: 141,890,845	S57P	probably benign	Het
Zbtb49	A	G	5: 38,213,241		probably benign	Het
Zfp758	A	G	17: 22,361,669	T30A	probably benign	Het

Other mutations in Col18a1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00952:Col18a1	APN	10	77069979	missense	possibly damaging	0.93
IGL01023:Col18a1	APN	10	77070975	missense	probably damaging	0.98
IGL01304:Col18a1	APN	10	77076141	unclassified	probably benign
IGL01519:Col18a1	APN	10	77059323	missense	probably damaging	0.99
IGL02217:Col18a1	APN	10	77053298	missense	probably damaging	0.96
IGL02275:Col18a1	APN	10	77059383	missense	possibly damaging	0.92
IGL02283:Col18a1	APN	10	77113109	missense	possibly damaging	0.71
IGL02492:Col18a1	APN	10	77072021	splice site	probably benign
IGL02673:Col18a1	APN	10	77059163	missense	probably damaging	1.00
IGL02710:Col18a1	APN	10	77113312	missense	possibly damaging	0.92
IGL02850:Col18a1	APN	10	77096466	missense	probably damaging	0.98
IGL03085:Col18a1	APN	10	77059181	splice site	probably benign
IGL03102:Col18a1	APN	10	77067623	splice site	probably benign
IGL03139:Col18a1	APN	10	77113343	missense	possibly damaging	0.84
IGL03181:Col18a1	APN	10	77055698	missense	probably damaging	1.00
IGL03183:Col18a1	APN	10	77073754	missense	probably damaging	1.00
R0039:Col18a1	UTSW	10	77077168	missense	probably damaging	1.00
R0180:Col18a1	UTSW	10	77096517	missense	probably benign	0.33
R0225:Col18a1	UTSW	10	77088914	missense	possibly damaging	0.90
R0335:Col18a1	UTSW	10	77059363	missense	probably damaging	0.99
R0336:Col18a1	UTSW	10	77058736	missense	probably damaging	1.00
R1471:Col18a1	UTSW	10	77096206	missense	unknown
R1538:Col18a1	UTSW	10	77071336	missense	probably damaging	1.00
R1594:Col18a1	UTSW	10	77113036	missense	possibly damaging	0.51
R1631:Col18a1	UTSW	10	77059297	missense	probably damaging	0.99
R1774:Col18a1	UTSW	10	77059981	missense	probably damaging	0.96
R1934:Col18a1	UTSW	10	77112744	missense	possibly damaging	0.73
R1990:Col18a1	UTSW	10	77081154	missense	unknown
R1991:Col18a1	UTSW	10	77081154	missense	unknown
R1992:Col18a1	UTSW	10	77081154	missense	unknown
R2081:Col18a1	UTSW	10	77054185	missense	probably damaging	1.00
R2082:Col18a1	UTSW	10	77059293	missense	probably damaging	1.00
R2351:Col18a1	UTSW	10	77112704	missense	probably benign	0.00
R2510:Col18a1	UTSW	10	77096268	missense	unknown
R3076:Col18a1	UTSW	10	77088928	missense	possibly damaging	0.57
R3433:Col18a1	UTSW	10	77096268	missense	unknown
R3800:Col18a1	UTSW	10	77067387	nonsense	probably null
R3918:Col18a1	UTSW	10	77053358	missense	probably benign	0.05
R3981:Col18a1	UTSW	10	77088887	missense	probably damaging	0.99
R3983:Col18a1	UTSW	10	77088887	missense	probably damaging	0.99
R4182:Col18a1	UTSW	10	77058841	splice site	probably null
R4239:Col18a1	UTSW	10	77096167	missense	unknown
R5014:Col18a1	UTSW	10	77070960	critical splice donor site	probably null
R5107:Col18a1	UTSW	10	77077223	critical splice acceptor site	probably null
R5413:Col18a1	UTSW	10	77069476	missense	probably damaging	1.00
R5503:Col18a1	UTSW	10	77071620	missense	probably damaging	1.00
R5524:Col18a1	UTSW	10	77058724	missense	probably damaging	1.00
R5772:Col18a1	UTSW	10	77166343	missense	unknown
R5958:Col18a1	UTSW	10	77096397	missense	probably benign	0.01
R6280:Col18a1	UTSW	10	77112489	intron	probably benign
R6309:Col18a1	UTSW	10	77112742	intron	probably benign
R6603:Col18a1	UTSW	10	77063977	critical splice donor site	probably null
R6608:Col18a1	UTSW	10	77112794	intron	probably benign
R6890:Col18a1	UTSW	10	77113484	intron	probably benign
R6938:Col18a1	UTSW	10	77112499	intron	probably benign
R7002:Col18a1	UTSW	10	77166343	missense	unknown
R7154:Col18a1	UTSW	10	77072965	missense	probably benign	0.25
R7204:Col18a1	UTSW	10	77085276	missense	unknown
R7278:Col18a1	UTSW	10	77096284	missense	unknown
R7442:Col18a1	UTSW	10	77096238	missense	unknown
R7453:Col18a1	UTSW	10	77085210	splice site	probably null
R7597:Col18a1	UTSW	10	77113303	missense	unknown
R7615:Col18a1	UTSW	10	77067005	missense	probably damaging	1.00
R7671:Col18a1	UTSW	10	77085383	missense	unknown
R7696:Col18a1	UTSW	10	77085272	missense	unknown
R7719:Col18a1	UTSW	10	77078012	missense	probably benign	0.13
R7772:Col18a1	UTSW	10	77068386	splice site	probably null
R8077:Col18a1	UTSW	10	77080851	missense	unknown
R8085:Col18a1	UTSW	10	77088907	missense	unknown
R8097:Col18a1	UTSW	10	77112508	missense	unknown
R8117:Col18a1	UTSW	10	77059974	missense	probably benign	0.41
R8130:Col18a1	UTSW	10	77074450	missense	probably benign	0.03
R8151:Col18a1	UTSW	10	77112584	missense	unknown
R8379:Col18a1	UTSW	10	77053238	missense	probably benign	0.08
R8479:Col18a1	UTSW	10	77081154	missense	unknown
R8523:Col18a1	UTSW	10	77054234	missense	probably damaging	0.99
R8862:Col18a1	UTSW	10	77113210	nonsense	probably null
R9109:Col18a1	UTSW	10	77057370	missense	probably damaging	1.00
R9298:Col18a1	UTSW	10	77057370	missense	probably damaging	1.00
R9312:Col18a1	UTSW	10	77058772	missense	probably damaging	0.98
R9366:Col18a1	UTSW	10	77096424	missense	unknown
R9399:Col18a1	UTSW	10	77080750	missense	unknown
R9559:Col18a1	UTSW	10	77077796	missense	probably damaging	1.00
R9649:Col18a1	UTSW	10	77080839	missense	unknown
R9689:Col18a1	UTSW	10	77080744	nonsense	probably null
R9719:Col18a1	UTSW	10	77113598	missense	unknown
Z1176:Col18a1	UTSW	10	77055709	missense	possibly damaging	0.81
Z1176:Col18a1	UTSW	10	77112851	missense	unknown
Z1177:Col18a1	UTSW	10	77112838	missense	unknown

Predicted Primers

PCR Primer
(F):5'- CTGCTATGGCTTTGAGGGTACC -3'
(R):5'- TCACTGTGATAGGCCCTACC -3'

Sequencing Primer
(F):5'- GGTACCCACAACCTCATTGCTTAG -3'
(R):5'- CCTTGGAGAAGGGACTCTCTATGC -3'

Posted On

2018-09-12