MRPL4

Summary

MRPL4 (mitochondrial ribosomal protein L4, HGNC:14276) is a protein-coding gene on chromosome 19p13.2, encoding Large ribosomal subunit protein uL4m (Q9BYD3). It is a selective cancer dependency (DepMap: 83.8% of cell lines).

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Sequence analysis identified alternatively spliced variants that encode different protein isoforms.

Source: NCBI Gene 51073 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 30 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 83.8% of screened cell lines
• MANE Select transcript: NM_015956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14276
Approved symbol	MRPL4
Name	mitochondrial ribosomal protein L4
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CGI-28, uL4m
Ensembl gene	ENSG00000105364
Ensembl biotype	protein_coding
OMIM	611823
Entrez	51073

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000253099, ENST00000307422, ENST00000393733, ENST00000588502, ENST00000588963, ENST00000590150, ENST00000590669, ENST00000590702, ENST00000591054, ENST00000592071, ENST00000592514, ENST00000906087, ENST00000906088, ENST00000906089, ENST00000906090, ENST00000930029, ENST00000930030

RefSeq mRNA: 4 — MANE Select: NM_015956 NM_001411149, NM_015956, NM_146387, NM_146388

CCDS: CCDS12230, CCDS42499, CCDS92511

Canonical transcript exons

ENST00000253099 — 9 exons

Exon	Start	End
ENSE00000954281	10258609	10258685
ENSE00001060744	10254589	10254640
ENSE00001060754	10252551	10252701
ENSE00001317543	10256708	10256825
ENSE00001353685	10252214	10252310
ENSE00002926467	10259617	10260055
ENSE00003464161	10258222	10258328
ENSE00003491769	10252397	10252463
ENSE00003616923	10258413	10258522

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.3802 / max 955.1167, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173747	61.6029	1822
173745	13.6466	1772
173746	0.7072	433
173748	0.4235	232

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.74	gold quality
mucosa of transverse colon	UBERON:0004991	96.16	gold quality
lower esophagus mucosa	UBERON:0035834	95.59	gold quality
right atrium auricular region	UBERON:0006631	95.30	gold quality
right adrenal gland	UBERON:0001233	95.22	gold quality
left adrenal gland	UBERON:0001234	95.13	gold quality
right adrenal gland cortex	UBERON:0035827	95.06	gold quality
right lobe of liver	UBERON:0001114	95.02	gold quality
heart left ventricle	UBERON:0002084	95.02	gold quality
left adrenal gland cortex	UBERON:0035825	94.97	gold quality
cardiac ventricle	UBERON:0002082	94.71	gold quality
skin of abdomen	UBERON:0001416	94.46	gold quality
skin of leg	UBERON:0001511	94.37	gold quality
esophagus mucosa	UBERON:0002469	94.28	gold quality
gastrocnemius	UBERON:0001388	94.27	gold quality
transverse colon	UBERON:0001157	94.12	gold quality
adrenal cortex	UBERON:0001235	94.06	gold quality
lower esophagus	UBERON:0013473	94.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.05	gold quality
right frontal lobe	UBERON:0002810	93.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.92	gold quality
right ovary	UBERON:0002118	93.91	gold quality
esophagus	UBERON:0001043	93.84	gold quality
cardiac atrium	UBERON:0002081	93.82	gold quality
body of stomach	UBERON:0001161	93.78	gold quality
prefrontal cortex	UBERON:0000451	93.73	gold quality
metanephros cortex	UBERON:0010533	93.72	gold quality
oocyte	CL:0000023	93.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.63

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• there is a strong association between allergic rhinitis risk and polymorphisms of MRPL4 and TNF-alpha genes in the Han Chinese population (PMID:23472126)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl4	ENSDARG00000058824
mus_musculus	Mrpl4	ENSMUSG00000003299
rattus_norvegicus	Mrpl4	ENSRNOG00000020659
drosophila_melanogaster	mRpL4	FBGN0001995
caenorhabditis_elegans		WBGENE00020717

Protein

Protein identifiers

Large ribosomal subunit protein uL4m — Q9BYD3 (reviewed: Q9BYD3)

Alternative names: 39S ribosomal protein L4, mitochondrial

All UniProt accessions (7): Q9BYD3, K7EJ73, K7EKI4, K7ELF1, K7ELQ0, K7ES61, X6RAY8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the mitochondrial large ribosomal subunit (mt-LSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins. Interacts with MIEF1 upstream open reading frame protein.

Subcellular location. Mitochondrion.

Similarity. Belongs to the universal ribosomal protein uL4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYD3-1	1, isoform a	yes
Q9BYD3-2	2, isoform b

RefSeq proteins (4): NP_001398078, NP_057040, NP_666499, NP_666500 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002136	Ribosomal_uL4	Family
IPR013005	Ribosomal_uL4-like	Family
IPR023574	Ribosomal_uL4_dom_sf	Homologous_superfamily

Pfam: PF00573

UniProt features (29 total): strand 15, helix 8, splice variant 2, chain 1, region of interest 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

87 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OF0	ELECTRON MICROSCOPY	2.2
7QI4	ELECTRON MICROSCOPY	2.21
8RRI	ELECTRON MICROSCOPY	2.4
8QU5	ELECTRON MICROSCOPY	2.42
9OLF	ELECTRON MICROSCOPY	2.46
7OF7	ELECTRON MICROSCOPY	2.5
7PO4	ELECTRON MICROSCOPY	2.56
6ZM6	ELECTRON MICROSCOPY	2.59
7O9M	ELECTRON MICROSCOPY	2.6
7OF6	ELECTRON MICROSCOPY	2.6
9CN3	ELECTRON MICROSCOPY	2.62
7QI5	ELECTRON MICROSCOPY	2.63
7OF2	ELECTRON MICROSCOPY	2.7
7OF3	ELECTRON MICROSCOPY	2.7
7OF4	ELECTRON MICROSCOPY	2.7
8QU1	ELECTRON MICROSCOPY	2.74
9PR4	ELECTRON MICROSCOPY	2.77
9PRA	ELECTRON MICROSCOPY	2.83
8ANY	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7QH7	ELECTRON MICROSCOPY	2.89
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8K2A	ELECTRON MICROSCOPY	2.9
8OIT	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYD3-F1	84.46	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 147

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5368286	Mitochondrial translation initiation
R-HSA-5389840	Mitochondrial translation elongation
R-HSA-5419276	Mitochondrial translation termination
R-HSA-9937383	Mitochondrial ribosome-associated quality control
R-HSA-392499	Metabolism of proteins
R-HSA-5368287	Mitochondrial translation
R-HSA-72766	Translation

MSigDB gene sets: 142 (showing top): GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, RICKMAN_METASTASIS_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOCC_MITOCHONDRIAL_ENVELOPE, PARK_HSC_AND_MULTIPOTENT_PROGENITORS, SENESE_HDAC3_TARGETS_DN, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (2): mitochondrial translation (GO:0032543), translation (GO:0006412)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial large ribosomal subunit (GO:0005762), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	4
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	1
translation	1
mitochondrial gene expression	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
structural molecule activity	1
ribosome	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

4522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL4	MRPL21	Q7Z2W9	717
MRPL4	MRPL13	Q9BYD1	712
MRPL4	MRPL17	Q9NRX2	708
MRPL4	MRPL11	Q9Y3B7	686
MRPL4	MRPL24	Q96A35	645
MRPL4	MRPL47	Q9HD33	623
MRPL4	MRPL19	P49406	612
MRPL4	MRPL48	Q96GC5	585
MRPL4	TUFM	P49411	584
MRPL4	TSFM	P43897	575
MRPL4	MRPL1	Q9BYD6	567
MRPL4	MRPS16	Q9Y3D3	546
MRPL4	MRPL36	Q9P0J6	526
MRPL4	MRPL12	P52815	518
MRPL4	UQCRFS1	P47985	500

IntAct

133 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
CLK2	MRPL4	psi-mi:“MI:0915”(physical association)	0.560
MRPL4	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	MRPL4	psi-mi:“MI:0915”(physical association)	0.560
MRPL4	CLK2	psi-mi:“MI:0915”(physical association)	0.560
MRPL4	LITAF	psi-mi:“MI:0915”(physical association)	0.560
TEFM	POLRMT	psi-mi:“MI:0914”(association)	0.560
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL27	MRPL33	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
MRPL4	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
NP	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
NP	HNRNPAB	psi-mi:“MI:0914”(association)	0.350
NP	KPNA4	psi-mi:“MI:0914”(association)	0.350
NP	KPNA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (518): MRPL4 (Two-hybrid), MRPL4 (Two-hybrid), MRPL4 (Affinity Capture-MS), MRPL4 (Affinity Capture-MS), MRPL4 (Affinity Capture-MS), MRPL4 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), YARS2 (Affinity Capture-MS), AMER1 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), MRPL46 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), NGRN (Affinity Capture-MS), WDR26 (Affinity Capture-MS), PTCD1 (Affinity Capture-MS)

ESM2 similar proteins: A9X1A9, G1SVW5, P02385, P08429, P0C2C1, P82675, P82915, P82919, P82923, Q0VFH6, Q1JQ99, Q2KID9, Q2TA12, Q2TBK2, Q2TBR2, Q32PI6, Q3MHY7, Q3SYS1, Q498T4, Q503X2, Q5RDW1, Q5REY4, Q5T653, Q641X9, Q6P1L8, Q7M0E7, Q7Z2W9, Q7Z7H8, Q800L1, Q90YV0, Q924T2, Q99N85, Q99N87, Q99N94, Q9BYC9, Q9BYD1, Q9BYD2, Q9BYD3, Q9CPX7, Q9CQL4

Diamond homologs: A0ALW7, A0LIJ1, A0PXU7, A0R8I1, A3DJH3, A4IJJ0, A4J112, A5D5J1, A5IM84, A5V601, A6LLL4, A6LPR2, A7GK21, A7Z0N9, A8F4R2, A8F986, A8YXK6, A9NED4, A9VP78, B0K5P4, B0KCK1, B0RZU1, B0TC57, B1HMX9, B1I1I9, B1LBN9, B1YGV1, B2A4E0, B3CN27, B3WAL6, B7GJ68, B7HJ49, B7HQU5, B7IT20, B7JKC0, B7K334, B8DB09, B8FET4, B8G1W7, B9IZJ5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL4	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial ribosome-associated quality control	29	40.0×	1e-37
Mitochondrial translation initiation	27	38.5×	1e-34
Mitochondrial translation elongation	27	38.5×	1e-34
Mitochondrial translation	24	37.1×	3e-30
Mitochondrial translation termination	27	33.3×	7e-33
Translation	25	17.4×	7e-23

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	27	38.8×	2e-33
translation	18	15.3×	4e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

30 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3248376	NC_000019.9:g.(?10244343)(11231218_?)del	Pathogenic
3248456	NC_000019.9:g.(?10244343)(10610709_?)del	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10252685:T:C	F87L	0.993
19:10252687:C:A	F87L	0.993
19:10252687:C:G	F87L	0.993
19:10259656:T:A	V260D	0.991
19:10258319:G:C	K181N	0.990
19:10258319:G:T	K181N	0.990
19:10254617:T:A	W102R	0.988
19:10254617:T:C	W102R	0.988
19:10252683:T:A	V86D	0.987
19:10252686:T:C	F87S	0.987
19:10258294:G:A	G173D	0.987
19:10258494:T:A	W212R	0.987
19:10258494:T:C	W212R	0.987
19:10256798:A:C	S140R	0.986
19:10256800:C:A	S140R	0.986
19:10256800:C:G	S140R	0.986
19:10258293:G:C	G173R	0.986
19:10258420:T:C	L187P	0.986
19:10258510:T:C	L217P	0.984
19:10259631:A:C	S252R	0.983
19:10259633:C:A	S252R	0.983
19:10259633:C:G	S252R	0.983
19:10252686:T:G	F87C	0.982
19:10258254:A:C	S160R	0.982
19:10258256:T:A	S160R	0.982
19:10258256:T:G	S160R	0.982
19:10259624:T:A	N249K	0.982
19:10259624:T:G	N249K	0.982
19:10258317:A:G	K181E	0.979
19:10259659:T:C	L261P	0.979

dbSNP variants (sampled 300 via entrez): RS1000048519 (19:10257153 T>C), RS1000172059 (19:10253590 A>C), RS1000172980 (19:10250456 CA>C,CAA), RS1000224272 (19:10253773 C>G,T), RS1000229903 (19:10251590 A>G,T), RS1000509663 (19:10252906 G>A), RS1000577061 (19:10251851 G>A), RS1001522623 (19:10258805 C>A), RS1001688261 (19:10253257 A>G), RS1002052378 (19:10259557 T>C), RS1002071269 (19:10253649 G>T), RS1002134627 (19:10254174 G>A), RS1002235951 (19:10253935 G>C), RS1002421837 (19:10254533 G>A,C,T), RS1002508964 (19:10257624 T>C)

Disease associations

OMIM: gene MIM:611823 | disease phenotypes: MIM:143890, MIM:611521

GenCC curated gene-disease

Mondo (2): familial hypercholesterolemia (MONDO:0005439), immunodeficiency 35 (MONDO:0012682)

Orphanet (1): Susceptibility to infection due to TYK2 deficiency (Orphanet:331226)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31
GCST005998_25	Alanine transaminase levels	2.000000e-08
GCST007096_89	Pulse pressure	4.000000e-08
GCST011352_8	Alanine aminotransferase levels	2.000000e-10
GCST90002394_439	Monocyte percentage of white cells	4.000000e-12
GCST90013406_123	Liver enzyme levels (alkaline phosphatase)	3.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0005763	pulse pressure measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566928	Tyrosine Kinase 2 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	4
sodium arsenite	decreases expression, increases expression	3
Phenylmercuric Acetate	increases expression, affects cotreatment	2
TAK-243	increases sumoylation	1
beauvericin	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
mercuric bromide	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Hydrogen Peroxide	increases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

110 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	PHASE2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	PHASE2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	PHASE2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia
NCT04941599	PHASE2	RECRUITING	2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
NCT05261126	PHASE2	COMPLETED	A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
NCT00004809	PHASE1	COMPLETED	Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia
NCT02709850	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
NCT03747224	PHASE1	COMPLETED	Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients
NCT05043181	PHASE1	NOT_YET_RECRUITING	Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH
NCT05851066	PHASE1	COMPLETED	A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers
NCT02048410	PHASE1/PHASE2	COMPLETED	Efficacy of a New Symbiotic Formulation in Children With Familial Hypercholesterolemia
NCT02100839	PHASE1/PHASE2	COMPLETED	Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results