Mutation:LDLR

Other Links
NCBI Entrez Gene
UCSD GoldenPath

Low-Density Lipoprotein Receptor (LDLR)

Chromosomal Location

19p13.3 (Lindgren V et al. PNAS 1985, 82(24):8567)

LDLR is the most intensively analyzed gene in patients with primary hyperlipidemia. It has 18 exons.

Well known mutations related with Familial Hypercholesterolemia (FH)

C317S in exon 7

P664L in exon 14

K790X in exon 17

Statistics

Registered number of mutations ... 73

• Single nucleotide substitution ... 47
• Deletion ... 18
• Insertion ... 8
• Deletion & Insertion ... 1

Mutation at each exon

	ligand binding domain (280 AA)					33 % identical to the human epidermal growth factor (400 AA)								O-linked sugar	membrane spanning	cytoplasmic domain
ex1	ex2	ex3	ex4	ex5	ex6	ex7	ex8	ex9	ex10	ex11	ex12	ex13	ex14	ex15	ex16	ex17	ex18
0	7	5	12	2	1	5	4	7	2	3	3	3	5	4	3	2	0

Mutation at introns ... 5

Reported Mutations

Page	Position	Structure	Mutation	Name	Nucleotide change	Effect on coding sequence	Class	Author	Reference
1655/T	T	exon16	1655delT		deletion of T at 1655	frame shift after Asp 530	NR	--
1867/3	3	exon13	1867delATC		deletion of ATC at 1867-1869	deletion of Ile at 602	NR	Yu W
1963/T	T	exon13	1963delT		deletion of T at 1963	frame shift	class 1	Hirayama T
2055/G	G	exon14	2055delG		deletion of G at 2055	frame shift	NR	Yu W
2199/2	2	exon15	2199delCA	Mishima	deletion of CA at 2199 or 2201	frame shift afgter Thr 713	NR	Tashiro J
230/G	G	exon3	230delG		deletion of G at 230	frame shift	NR	Yu W
355/7	7	exon4	355del7bp		deletion of GGGAAGT at 355	premature stop at codon 183	NR	Hattori H
Ex7-In14/13k	13k	exon7-14	Ex7-In14 del	Okayama	deletion of 13kb	deletion of exons 8-14	NR	Kajinami K
In1-In3/10k	10k	exon2-3	In1-In3 del	onami-2	deletion of 10kb	deletion of exons 2,3	class 3	Kajinami K
In1-In3/4k	4k	exon2-3	In1-In3 del		deletion of 4kb	deletion of exons 2,3	class 3	Yamakawa K
In1-In3/5k	5k	exon2-3	In1-In3 del		deletion of 5kb	deletion of exons 2,3	NR	Kigawa K
In1-In4/12k	12k	exon2-4	In1-In4 del	Kanazawa-1	deletion of 12kb	deletion of exons 2-4	NR	Kajinami K
In14-In15/6k	6k	exon15	In14-In15 del	Tonami-1	deletion of 6kb	deletion of exon 15	NR	Kajinami K
In14-In16/5.5k	5.5k	exon15-16	In14-In16 del		deletion of 5.5 kb	deletion of exons 15,16	NR	Yamakawa K
In15-In17/4k	4k	exon16-17	In15-In17 del		deletion of 4kb	deletion of exons 16, 17	NR	Yamakawa K
In15-In18/7.8k	7.8k	exon16-18	In15-In18 del	Osaka 1	deletion of 7.8 kb	deletion of exons 16-18	class 4B	Miyake Y
In6-In14/12k	12k	exon7-14	In6-In14 del	Osaka-2	deletion of 12kb	deletion of exons 8-14	class 5	Miyake Y
1115/9-6	9-6	exon8	1115del9bp,ins6bp		deletion of 9 bp insertion of 6 bp from 1115	GlyGlyGlyTry → AlaLeuAsn at 351	NR	Yamakawa K
1061/T	T	exon8	1061InsT		insertion of T at 1061	frame shift	NR	Yu W
1246/5	5	exon9	1246ins5bp		insertion of 5 bp at 1246	frame shift after Arg395	NR	Varret M
1687/C	C	exon11	1687insC		insertion of C at 1687	premature stop at codon 559	NR	Hattori H
1773/G	G	exon12	1773insG		insertion of G at 1773	frame shift	class 1	Hirayama T
2035/T	T	exon14	2035insT		insertion of T at 2035	premature stop at codon 696	NR	Hattori H
2412/G	G	exon17	2412insG		insertion of G after 2412	frame shift after Gly 784	NR	Miyake Y
327/C	C	exon4	327insC		insertion of C at 327	premature stop at codon 158	NR	Hirota R
389/C	C	exon4	389insC		insertion of C at 389	frame shift	NR	Yu W
1012/T-A	T-A	exon7	C317S	Wakayama	1012 T-A	cys → Ser at 317	class 2	Funahashi T
1012/T-C	T-C	exon7	C317R	Gifu	1012 T-C	cys → Arg at 317	NR	Varret M
1048/C-T	C-T	exon7	R329X	Gifu	1048 C-T	Arg → Stop at 329	NR	Yu W
1066/G-C	G-C	exon8	D335H	Kanagawa	1066 G-C	Asp → His at 335	NR	Varret M
1136/G-A	G-A	exon8	C358Y		1136 G-A	Cys → Tyr at 358	class 5	Hirayama T
1207/T-A	T-A	exon9	F382L		1207 T-A	Phe → Leu at 382	NR	Varret M
1246/C-T	C-T	exon9	R395W	Morioka	1246 C-T	Arg → Trp at 395	defective	Yagi K
1252/G-A	G-A	exon9	E397K		1252 G-A	Glu → Lys at 397	NR	Yu W
1285/G-A	G-A	exon9	V408M	Afrikaner-2	1285 G-A	Val → Met at 408	NR	Varret M
1291/G-A	G-A	exon9	A410T		1291 G-A	Ala → Thr at 410	NR	Hattori H
1297/G-C	G-C	exon9	D412H	Osaka-3	1297 G-C	Asp → His at 412	class 2	Miyake Y
132/G-A	G-A	exon2	W23X	nanao	132 G-A	Trp → Stop at 23	NR	Yu W
137/G-A	G-A	exon2	C25Y		137 G-A	Cys → Try at 25	NR	Yu W
139/G-A	G-A	exon2	D26N		139 G-A	Asp → Asn at 26	NR	Varret M
1502/C-A	C-A	exon10	A480E		1502 C-A	Ala → Glu at 480	class 2B	Miyake Y
1567/G-A	G-A	exon10	V502M		1567 G-A	Val → Met at 502	class 2A	Yu W
1587-1/G-A	G-A	intron10	1587-1 G-A		1587-1 G-A	3' splice signal	NR	Yu W
1599/G-A	G-A	exon11	W512X		1599 G-A	Trp → Stop at 512	NR	Hattori H
1702/C-G	C-G	exon11	L547V		1702 C-G	Leu → Val at 547	NR	Hattori H
1705+1/G-C	G-C	intron11	1705+1 G-C		1705+1 G-C	5' splice signal	class 1	Miyake Y
1784/G-A	G-A	exon12	R574Q		1784 G-A	Arg → Gln at 574	NR	Varret M
1822/C-T	C-T	exon12	P587S		1822 C-T	Pro → Ser at 587	class 2	Hirayama T
1845+2/T-C	T-C	intron12	1845+2 T-C	Niigata	1845+2 T-C	5' splice signal	class 1	Maruyama T
1925/T-G	T-G	exon13	L621S		1925 T-G	Leu → Ser at 621	NR	Yu W
2026/G-A	G-A	exon14	G655S		2026 G-A	Gly → Ser at 655	NR	Yu W
2054/C-T	C-T	exon14	P664L	Kanazawa-2	2054 C-T	Pro→ Leu at 664	class 2B	Soutar AK
2140/G-A	G-A	exon14	E693K		2140 G-A	Glu → Lys at 693	NR	Hattori H
2215/C-T	C-T	exon15	Q718X	Yokote	2215 C-T	Gln → Stop at 718	NR	Higashikata T
223/T-A	T-A	exon3	C54S		223 T-A	Cys → Tyr at 54	class 2	Emi M
2312-3/C-A	C-A	intron15	2312-3 C-A		2312-3 C-A	3' splice signal	NR	Yu W
2431/A-T	A-T	exon17	K790X		2431 A-T	Lys → Stop at 790	class 1,4	Maruyama T
244/G-T	G-T	exon3	C61F		244 G-T	Cys → Phe at 61	NR	Yu W
285/C-A	C-A	exon3	C74X		285 C-A	Cys → Stop at 74	class 1	Hirayama T
288/G-T	G-T	exon3	C74F		288 G-T	Cys → Phe at 74	NR	Yu W
344/G-A	G-A	exon4	R94H	Fukuoka	344 G-A	Arg → His at 94	NR	Varret M
361/T-G	T-G	exon4	C100G		361 T-G	Cys → Gly at 100	NR	Yu W
388/T-A	T-A	exon4	S109T		388 T-A	Ser → Thr at 109	NR	Yu W
418/G-A	G-A	exon4	E119K	Philipines	418 G-A	Glu → Lys at 119	class 2B	Hobbs HH
463/T-C	T-C	exon4	C134R		463 T-C	Cys → Arg at 134	NR	Yu W
478/T-C	T-C	exon4	C139R		478 T-C	Cys → Arg at 139	NR	Yu W
550/T-C	T-C	exon4	C163R		550 T-C	Cys → Arg at 163	NR	Yu W
565/G-A	G-A	exon4	V168M		565 G-A	Val → Met at 168	NR	Yu W
611/G-C	G-C	exon4	C183S		611 G-C	Cys → Ser at 183	NR	Yu W
68-1/G-C	G-C	intron1	68-1 G-C		68-1 G-C	3' splice signal	class 1	Maruyama T
796/G-A	G-A	exon5	D245N	Naha	796 G-A	Asp → Asn at 245	NR	Yu W
797/A-G	A-G	exon5	D245G		797 A-G	Asp → Gly at 245	NR	Yu W
901/G-T	G-T	exon6	D280Y	Tsuruga	901 G-T	Asp → Tyr at 280	NR	Yu W