Mutagenetix > Incidental Mutation

Incidental Mutation 'R4910:Mlc1'

379447

Institutional Source

Beutler Lab

Gene Symbol

Mlc1

Ensembl Gene

ENSMUSG00000035805

Gene Name

megalencephalic leukoencephalopathy with subcortical cysts 1 homolog (human)

Synonyms

WKL1, Kiaa0027-hp

MMRRC Submission

042512-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4910 (G1)

Quality Score

148

Status

Validated

Chromosome

Chromosomal Location

88955884-88979007 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 88958212 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 315 (L315P)

Ref Sequence

ENSEMBL: ENSMUSP00000104993 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000042594] [ENSMUST00000109368] [ENSMUST00000109371] [ENSMUST00000177180]

AlphaFold

Q8VHK5

Predicted Effect

possibly damaging
Transcript: ENSMUST00000042594
AA Change: L309P

PolyPhen 2 Score 0.935 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000047667
Gene: ENSMUSG00000035805
AA Change: L309P

Domain	Start	End	E-Value	Type
transmembrane domain	57	79	N/A	INTRINSIC
transmembrane domain	119	141	N/A	INTRINSIC
transmembrane domain	148	170	N/A	INTRINSIC
transmembrane domain	203	225	N/A	INTRINSIC
transmembrane domain	234	256	N/A	INTRINSIC
transmembrane domain	266	288	N/A	INTRINSIC
transmembrane domain	308	330	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109368
AA Change: L315P

PolyPhen 2 Score 0.935 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000104993
Gene: ENSMUSG00000035805
AA Change: L315P

Domain	Start	End	E-Value	Type
transmembrane domain	63	85	N/A	INTRINSIC
transmembrane domain	125	147	N/A	INTRINSIC
transmembrane domain	154	176	N/A	INTRINSIC
transmembrane domain	209	231	N/A	INTRINSIC
transmembrane domain	240	262	N/A	INTRINSIC
transmembrane domain	272	294	N/A	INTRINSIC
transmembrane domain	314	336	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000109371

SMART Domains

Protein: ENSMUSP00000104996
Gene: ENSMUSG00000022388

Domain	Start	End	E-Value	Type
low complexity region	4	14	N/A	INTRINSIC
low complexity region	273	285	N/A	INTRINSIC
Pfam:TTL	324	621	3.9e-74	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000177180

SMART Domains

Protein: ENSMUSP00000135381
Gene: ENSMUSG00000022388

Domain	Start	End	E-Value	Type
low complexity region	4	14	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177254

Meta Mutation Damage Score

0.5240

Coding Region Coverage

1x: 98.9%
3x: 97.9%
10x: 94.6%
20x: 86.1%

Validation Efficiency

95% (144/151)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The function of this gene product is unknown; however, homology to other proteins suggests that it may be an integral membrane transporter. Mutations in this gene have been associated with megalencephalic leukoencephalopathy with subcortical cysts, an autosomal recessive neurological disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit myelin vacuolization that progresses with age, and show alterations in glial cell and oligodendrocyte physiology. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 123 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4932438A13Rik	C	A	3: 36,998,199	T3016K	probably damaging	Het
Adam3	T	A	8: 24,694,305	I560L	probably benign	Het
Agxt	T	C	1: 93,135,714	F113L	probably benign	Het
Aknad1	T	A	3: 108,781,252		probably null	Het
Alpk2	T	A	18: 65,266,286	K2074*	probably null	Het
Apob	A	G	12: 8,007,848	Y2077C	probably damaging	Het
Arhgap17	A	T	7: 123,308,377	L254Q	probably damaging	Het
Arhgap26	T	A	18: 38,993,637		probably benign	Het
Arhgef5	A	G	6: 43,272,828	D171G	probably benign	Het
Arid1b	T	A	17: 5,342,203	S2003T	probably damaging	Het
Armc5	T	G	7: 128,240,728	L406R	possibly damaging	Het
Arsb	T	C	13: 93,771,977	V67A	probably benign	Het
Aspm	A	G	1: 139,491,543	Y2982C	probably damaging	Het
Btbd7	A	G	12: 102,808,048	L487P	probably damaging	Het
Card11	C	G	5: 140,874,414	D1063H	probably damaging	Het
Ccdc186	G	A	19: 56,798,691	T615M	probably damaging	Het
Cd101	T	A	3: 100,993,889	T960S	probably benign	Het
Cdca7l	C	A	12: 117,873,785	S191*	probably null	Het
Cemip	A	T	7: 83,997,411	I143N	probably damaging	Het
Cep170	C	T	1: 176,782,263	E161K	possibly damaging	Het
Chrm2	A	T	6: 36,524,233	T342S	probably benign	Het
Cib2	A	G	9: 54,549,879	F34L	probably benign	Het
Cnot1	A	T	8: 95,733,231	I1836N	probably benign	Het
Col4a3	C	A	1: 82,672,679	P552Q	unknown	Het
Cp	T	A	3: 19,989,224		probably benign	Het
Cul3	C	T	1: 80,290,089	V112I	probably benign	Het
Dcdc5	A	G	2: 106,365,550		noncoding transcript	Het
Disp1	A	T	1: 183,135,463	V133E	probably damaging	Het
Dlg4	A	G	11: 70,030,925	D30G	probably damaging	Het
Dopey1	C	T	9: 86,492,061	T191I	probably damaging	Het
Enam	T	G	5: 88,502,314	S561A	probably benign	Het
Fbxw8	G	T	5: 118,125,027		probably null	Het
Filip1	A	G	9: 79,817,932	V1135A	probably benign	Het
Galnt6	T	C	15: 100,716,178	T81A	probably benign	Het
Ghdc	T	C	11: 100,766,988	K472E	probably benign	Het
Gm10568	T	G	1: 3,680,941		noncoding transcript	Het
Gm4788	T	G	1: 139,774,563	D61A	probably damaging	Het
Gm4953	T	A	1: 159,168,359		noncoding transcript	Het
Gm6871	T	A	7: 41,573,592	H24L	probably benign	Het
Gm8298	T	A	3: 59,869,014		probably null	Het
Gpr155	G	A	2: 73,367,538	Q413*	probably null	Het
Grhl2	A	G	15: 37,291,676		probably null	Het
Ighv1-31	G	C	12: 114,829,508	S36*	probably null	Het
Ighv8-5	A	G	12: 115,067,842	S26P	probably damaging	Het
Igkv17-134	A	C	6: 67,720,926		probably benign	Het
Igkv5-48	A	C	6: 69,726,849	L24R	probably damaging	Het
Isg20l2	T	A	3: 87,939,263	V340E	probably damaging	Het
Lrrtm1	A	G	6: 77,244,901	Y447C	probably damaging	Het
Ltbp1	T	C	17: 75,327,292	S855P	probably damaging	Het
Mgat4e	A	T	1: 134,541,864	N147K	probably damaging	Het
Mrgpra2a	A	G	7: 47,426,544	V322A	probably benign	Het
Mroh7	T	C	4: 106,709,955		probably null	Het
Mybpc1	T	A	10: 88,555,724	K304*	probably null	Het
Nlrp14	A	C	7: 107,186,583	D622A	possibly damaging	Het
Nlrp1b	T	A	11: 71,217,277	H466L	probably benign	Het
Nlrp4d	T	A	7: 10,378,409		noncoding transcript	Het
Nrxn3	A	G	12: 89,260,360	E628G	possibly damaging	Het
Nup133	T	C	8: 123,927,131	R530G	possibly damaging	Het
Nup98	A	G	7: 102,195,800	S21P	unknown	Het
Olfr1307	A	T	2: 111,945,078	I126K	possibly damaging	Het
Olfr168	T	C	16: 19,530,018	T301A	probably benign	Het
Olfr173	T	A	16: 58,797,442	T135S	probably benign	Het
Olfr251	T	A	9: 38,378,742	V287E	probably null	Het
Olfr671	G	A	7: 104,975,479	P169S	possibly damaging	Het
Olfr753-ps1	T	C	17: 37,170,043	I202V	probably benign	Het
Olfr798	T	C	10: 129,625,807	T85A	probably damaging	Het
Otog	A	T	7: 46,264,062	Y773F	probably damaging	Het
Otog	A	T	7: 46,298,534	I2320F	probably damaging	Het
Otogl	T	C	10: 107,879,517	S433G	probably benign	Het
Pcdhb17	A	T	18: 37,485,159	M1L	possibly damaging	Het
Pde7b	T	A	10: 20,724,734		probably benign	Het
Pgm2	T	C	4: 99,963,527	V207A	probably damaging	Het
Pkd1	T	A	17: 24,572,687	V1116E	probably damaging	Het
Pkd1l1	T	A	11: 8,929,360	Y497F	possibly damaging	Het
Pomgnt2	T	C	9: 121,982,947	N256S	probably benign	Het
Pot1a	A	T	6: 25,746,021		probably benign	Het
Prdm9	T	C	17: 15,544,323	T732A	probably benign	Het
Prg4	T	A	1: 150,455,823		probably benign	Het
Ptpro	T	C	6: 137,368,338	V114A	probably damaging	Het
Pyurf	A	G	6: 57,691,948	S20P	unknown	Het
Rasgrf1	A	G	9: 89,976,752	T488A	probably benign	Het
Rassf8	A	T	6: 145,815,280	K111*	probably null	Het
Reps1	A	T	10: 18,107,688	E426D	probably damaging	Het
Robo2	T	C	16: 73,933,778	K982R	probably damaging	Het
Rps23	T	C	13: 90,923,752		probably null	Het
Scamp4	T	A	10: 80,609,671	V56E	probably damaging	Het
Serpina1c	C	T	12: 103,895,032	V408I	probably benign	Het
Sigirr	A	G	7: 141,093,788	W49R	probably damaging	Het
Slc17a6	A	T	7: 51,658,741	H271L	possibly damaging	Het
Slc7a5	G	T	8: 121,885,122	T389K	probably damaging	Het
Slf1	T	A	13: 77,043,880	H945L	probably benign	Het
Slit3	T	C	11: 35,632,722	S662P	probably damaging	Het
Snta1	C	A	2: 154,377,018	E466*	probably null	Het
Sowaha	A	G	11: 53,478,445	L488P	probably damaging	Het
Spata17	C	A	1: 187,194,011	V41F	probably damaging	Het
Spta1	T	A	1: 174,217,863		probably null	Het
Srrm2	T	A	17: 23,815,388		probably benign	Het
Stard13	T	C	5: 151,062,527	N388S	probably benign	Het
Stmn3	T	C	2: 181,308,837	K59E	probably damaging	Het
Sval1	A	G	6: 41,955,444	N76S	probably benign	Het
Svep1	T	C	4: 58,096,276	H1448R	possibly damaging	Het
Sycp2	A	T	2: 178,358,224	D986E	probably benign	Het
Sytl5	C	T	X: 9,915,602	P181L	possibly damaging	Het
Tbkbp1	G	A	11: 97,139,130	S400L	probably benign	Het
Tesc	G	T	5: 118,056,466		probably benign	Het
Tjp1	C	T	7: 65,343,727	G33R	probably damaging	Het
Tlr11	C	A	14: 50,362,889	F777L	probably benign	Het
Tmem156	A	G	5: 65,091,462		probably benign	Het
Top3a	A	G	11: 60,752,378		probably benign	Het
Tpcn1	A	G	5: 120,556,519	W162R	probably damaging	Het
Tpd52l2	A	T	2: 181,515,212		probably benign	Het
Trim80	G	A	11: 115,446,455	G381D	probably damaging	Het
Ugt1a10	C	T	1: 88,215,123	P113L	probably damaging	Het
Vmn2r117	TC	T	17: 23,479,513		probably null	Het
Vmn2r56	T	A	7: 12,715,535	I259F	possibly damaging	Het
Vmn2r59	T	C	7: 42,043,653	T508A	probably benign	Het
Wdr73	A	G	7: 80,891,708	V362A	probably damaging	Het
Zdhhc21	G	T	4: 82,820,331	T207K	possibly damaging	Het
Zfp120	T	A	2: 150,117,952	Q150L	probably damaging	Het
Zfp212	C	A	6: 47,931,499	Q471K	possibly damaging	Het
Zfp804b	C	T	5: 6,770,540	G841D	possibly damaging	Het
Znfx1	A	T	2: 167,036,804	M1884K	probably damaging	Het
Znfx1	G	T	2: 167,037,482	A1658D	probably benign	Het

Other mutations in Mlc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01634:Mlc1	APN	15	88974718	splice site	probably benign
IGL03251:Mlc1	APN	15	88974731	missense	possibly damaging	0.88
R0710:Mlc1	UTSW	15	88977864	missense	possibly damaging	0.88
R1037:Mlc1	UTSW	15	88965461	missense	probably damaging	1.00
R1573:Mlc1	UTSW	15	88958147	missense	probably damaging	1.00
R1994:Mlc1	UTSW	15	88974579	missense	possibly damaging	0.50
R2121:Mlc1	UTSW	15	88963431	missense	probably benign	0.22
R2302:Mlc1	UTSW	15	88965437	missense	possibly damaging	0.63
R3110:Mlc1	UTSW	15	88965996	missense	probably benign	0.00
R3112:Mlc1	UTSW	15	88965996	missense	probably benign	0.00
R3117:Mlc1	UTSW	15	88976528	missense	probably damaging	1.00
R4027:Mlc1	UTSW	15	88966494	missense	probably benign	0.29
R4450:Mlc1	UTSW	15	88963490	missense	probably benign	0.19
R4576:Mlc1	UTSW	15	88974537	missense	probably damaging	1.00
R4697:Mlc1	UTSW	15	88974777	missense	probably damaging	1.00
R4728:Mlc1	UTSW	15	88978031	splice site	probably null
R5618:Mlc1	UTSW	15	88974566	missense	probably damaging	1.00
R7528:Mlc1	UTSW	15	88974507	missense	possibly damaging	0.95
R7746:Mlc1	UTSW	15	88964170	missense	probably damaging	0.99
R7885:Mlc1	UTSW	15	88977904	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- GGAAGGATCCATAACCTCACAAGG -3'
(R):5'- ACAACCTGGGTCCTCTGTATG -3'

Sequencing Primer
(F):5'- TCACAAGGACCCTCTGAGG -3'
(R):5'- GCTTACTCATTAAATGGAAGGCAGC -3'

Posted On

2016-04-15