Table 1 Location of all reported variants 270 bp upstream from LDLR start of translation, with reported effect on promoter activity and homology across human and 6 primate and 6 mammalian species (variants tested in this study are shown in bold)

From: Functional analysis of four LDLR 5′UTR and promoter variants in patients with familial hypercholesterolaemia

Variant

Promoter activity (% of wt)

Location

Sequence homology a

Reference

c.-268G>T

In FH and normal

1 bp from FP1

7/8

20

c.-220_-221insA

Not tested

FP1

NA

21

c.-217C>T

160% Luciferase

2 bp from FP1

13/13

20

c.-215A>G

100% Luciferase

4 bp from FP1

11/12

6

c.-208A>T

100% Luciferase

Between SREBP1 and FP1

12/12

15

c.-206C>T

Not tested

Between SREBP1 and FP1

13/13

22

c.-193_-186delinsTG

Not tested

SREBP1

NA

23

c.-188C>T

Not tested

SREBP1

13/13

23

c.-185_-183delCTT

10% Luciferase

SREBP1

NA

24

c.-156C>T

Not testedb

SREBP2

13/13

25

c.-155_-154delinsTTCTGCAAACTCCT

11% Luciferase

SREBP2

NA

15

c.-153C>T

Not tested

SREBP2

13/13

26

c.-152C>T

40% Luciferase

SREBP2

13/13

20

c.-146C>A

Not tested

Between SREBP2 and SP1

13/13

27

c.-142C>T

20% Luciferase

SP1

13/13

28

c.-140C>G

7% Luciferase

SP1

13/13

15

c.-140C>T

6% Luciferase

SP1

13/13

15

c.-139C>A

Not tested

SP1

13/13

23

c.-139C>G

26% Luciferase

SP1

13/13

8

c.-138delT

24% LDLR activity

SP1

12/13

29

c.-138T>C

25% Luciferase

SP1

12/13

30

c.-137C>T

Not testedc

SP1

13/13

31

c.-136C>G

12% Luciferase

SP1

13/13

15

c.-136C>T

5% CAT assay

SP1

13/13

32

c.-135C>G

Not testedd

SP1

13/13

31

c.-121T>C

72% Luciferase

Between TATA box and SP1

13/13

12

c.-120C>T

3% Luciferase

Between TATA box and SP1

13/13

26

c.-101T>C

64% Luciferase

TATA BOX

12/12

6

c.-88G>A

100% Luciferase

5′UTR

12/12

15

c.-68A>C

Not tested

5′UTR

5/11

33

c.-36T>G

100% Luciferase

5′UTR

6/10

15

c.-23A>C

Not tested

5′UTR

7/12

34

c.-22delC

Not tested

5′UTR

10/12

35

c.-14C>A

Not tested

5′UTR

9/12

27

c.-13A>G

100% Luciferase

5′UTR

8/13

11

c.-5C>T

Not tested

5′UTR

7/11

23

  1. Abbreviations: FP1, Foot Print 1; SREBP1, sterol regulating element-binding protein 1; SP1, Specificty Protein 1. Where the base for the sequence was not present in a particular species, the species was discounted from the total. The NG_009060.1 reference sequence was used.
  2. aLDLR promoter sequence conservation between Human, Pan troglodytes, Gorilla gorilla, Pongo abelii, Macaca mulatta, Callithrix jacchus, Oryctolagus cuniculus, Mus musculus, Rattus norvegicus, Bos taurus, Sus scrofa, Canis lupus familiaris and Equus caballus (http://www.ensembl.org/Homo_sapiens/Gene/Compara_Alignments?align=609&db=core&g=ENSG00000130164&r=19%3A11200057-11244506&t=ENST00000252444).
  3. bCosegregation with FH reported.
  4. c5–15% LDLR activity (when compound heterozygote with c.1222G>A, p.(Glu408Lys)).
  5. d5–15% LDLR activity in homozygote.
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