MYLIP

Summary

MYLIP (myosin regulatory light chain interacting protein, HGNC:21155) is a protein-coding gene on chromosome 6p22.3, encoding E3 ubiquitin-protein ligase MYLIP (Q8WY64). E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8.

The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth.

Source: NCBI Gene 29116 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 139 total
• MANE Select transcript: NM_013262

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21155
Approved symbol	MYLIP
Name	myosin regulatory light chain interacting protein
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	MIR, IDOL
Ensembl gene	ENSG00000007944
Ensembl biotype	protein_coding
OMIM	610082
Entrez	29116

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000349606, ENST00000356840, ENST00000718320, ENST00000718321

RefSeq mRNA: 1 — MANE Select: NM_013262 NM_013262

CCDS: CCDS4536

Canonical transcript exons

ENST00000356840 — 7 exons

Exon	Start	End
ENSE00000508443	16130557	16130747
ENSE00000848091	16143699	16143863
ENSE00000848092	16144897	16145317
ENSE00001283775	16129086	16129409
ENSE00001528068	16146662	16148248
ENSE00003464954	16143020	16143217
ENSE00003624670	16141625	16141810

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.3796 / max 1701.6299, expressed in 1696 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66084	34.2797	1696
66086	0.1000	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.76	gold quality
secondary oocyte	CL:0000655	99.70	gold quality
nipple	UBERON:0002030	97.93	gold quality
lower lobe of lung	UBERON:0008949	97.91	gold quality
mammary duct	UBERON:0001765	97.16	gold quality
synovial joint	UBERON:0002217	97.09	gold quality
renal medulla	UBERON:0000362	97.03	gold quality
saphenous vein	UBERON:0007318	96.99	gold quality
urethra	UBERON:0000057	96.93	gold quality
cardia of stomach	UBERON:0001162	96.86	gold quality
parietal pleura	UBERON:0002400	96.71	gold quality
sperm	CL:0000019	96.65	gold quality
skin of hip	UBERON:0001554	96.64	gold quality
visceral pleura	UBERON:0002401	96.59	gold quality
placenta	UBERON:0001987	96.48	gold quality
palpebral conjunctiva	UBERON:0001812	96.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.27	gold quality
trachea	UBERON:0003126	95.98	gold quality
vena cava	UBERON:0004087	95.92	gold quality
penis	UBERON:0000989	95.86	gold quality
mammalian vulva	UBERON:0000997	95.31	gold quality
pleura	UBERON:0000977	95.26	gold quality
pylorus	UBERON:0001166	95.14	gold quality
superior surface of tongue	UBERON:0007371	95.11	gold quality
epithelium of mammary gland	UBERON:0003244	94.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.98	gold quality
pharyngeal mucosa	UBERON:0000355	94.95	gold quality
adult organism	UBERON:0007023	94.89	gold quality
superficial temporal artery	UBERON:0001614	94.87	gold quality
epithelium of nasopharynx	UBERON:0001951	94.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-109979	no	62.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CNPY2, DNMT1, DNMT3B

miRNA regulators (miRDB)

127 targeting MYLIP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-17-5P	99.89	73.83	2665

Literature-anchored findings (GeneRIF, showing 35)

• MSAP interacts with this protein that enhances neurite outgrowth and increases myosin regulatory light chain in fetal and adult brain. (PMID:12826659)
• c-MIR is the first example of an E3 ubiquitin ligase that is capable of inhibiting major histocompatibility (MHC) class II expression in antigen-presenting cells; c-MIR might potently regulate immune responses in vivo. (PMID:16785530)
• study shows the LXR-Idol(Mylip)-LDLR axis defines a complementary pathway to sterol response element-binding proteins for sterol regulation of cholesterol uptake (PMID:19520913)
• Novel insights into the physiology of this receptor come from studies on the ubiquitination and degradation of LDL receptor by the ubiquitin ligase Mylip/Idol that is induced in cells by the nuclear receptor, LXR. (PMID:19688294)
• Data report that statins exert opposite effects on PCSK9 and Idol gene expression in human hepatoma-derived cell lines and primary hepatocytes isolated from hamsters and rats. (PMID:21069265)
• identify the IDOL-UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake (PMID:21685362)
• both the FERM and RING domains are required for promoting lysosomal degradation of the LDLR by IDOL. (PMID:21734303)
• N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans (PMID:21765216)
• expression levels rise with increasing age in hearts of men (PMID:22261164)
• FGF21 also enhanced expression of Canopy2 (Cnpy2)/MIR-interacting Saposin-like protein (Msap) that is known to interact with Mylip/Idol. (PMID:22378787)
• No association of the MYLIP rs9370867 genotypes with lipid profile, hemodynamic data, and coronary angiographic data was in a Brazilian population. (PMID:22741812)
• MYLIP rs3757354 SNP is associated with serum TC, HDL-C and ApoAI levels in the Bai Ku Yao and Han populations. But the association is different between the two ethnic groups. (PMID:23107276)
• Several lipid-related gene polymorphisms interact with overweight/obesity to modulate blood pressure levels. (PMID:23109900)
• Results show that IDOL contributes to variation in circulating levels of LDL-C. (PMID:23324548)
• IDOL is recruited to plasma membrane by low-density lipoprotein receptor (LDLR), promotes LDLR internalization in the absence of clathrin or caveolae, and facilitates LDLR degradation by shuttling it into the multivesicular body protein-sorting pathway (PMID:23382078)
• evidence for the existence of an LXR-IDOL-mediated internalization pathway for the LDLR that is distinct from that used for lipoprotein uptake (PMID:23733886)
• Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions in transgenic mice. (PMID:24935961)
• study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH. (PMID:25171759)
• IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population. (PMID:25927920)
• The study identified MARCH6 as a negative regulator of SREBP2-mediated transcription and described an unexpected E3 circuit functionally linking MARCH6 and IDOL to limit uptake of low-density lipoprotein via the LDLR pathway. (PMID:26527619)
• Specifically, loss of IDOL increases LDLR distribution in the hepatic cell, and subsequently reduces serum LDL-C levels in dyslipidemic patients (PMID:26601593)
• Identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL. (PMID:26666640)
• Data suggest inducible expression of IDOL is subject to robust, rapid regulation by process that is sensitive to deubiquitinase inhibition in human/mouse cell lines and primary human cells; transcriptional induction of IDOL leads to degradation of LDLR. (PMID:26719329)
• the effects caused by human inducible degrader of the low-density lipoprotein expression are LDLR- dependent given the unchanged plasma lipids in LAhB mice lacking low-density lipoprotein receptor (PMID:26786161)
• RP1-13D10.2 is a long noncoding RNA that regulates LDLR and may contribute to low-density lipoprotein cholesterol response to statin treatment. (PMID:27071970)
• The long noncoding RNA RP1-13D10.2 may contribute to LDL cholesterol levels in response to statins. (PMID:27071970)
• IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans. (PMID:31597442)
• Structural analysis of the LDL receptor-interacting FERM domain in the E3 ubiquitin ligase IDOL reveals an obscured substrate-binding site. (PMID:32727844)
• IDOL gene variant is associated with hyperlipidemia in Han population in Xinjiang, China. (PMID:32868861)
• SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1. (PMID:33154164)
• Identification of MYLIP gene and miRNA-802 involved in the growth and metastasis of cervical cancer cells. (PMID:33185588)
• Novel associations of SNPs MYLIP rs3757354 and ABCA1 2230806 gene with early-onset-preeclampsia: A case-control candidate genetic study. (PMID:33450693)
• Genetic polymorphism of IDOL gene was associated with the susceptibility of coronary artery disease in Han population in Xinjiang, China. (PMID:33845890)
• Mouse Spinal Cord Vascular Transcriptome Analysis Identifies CD9 and MYLIP as Injury-Induced Players. (PMID:37047406)
• Effect of type 2 diabetes on the inducible degrader of LDL receptor. (PMID:37094639)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mylipa	ENSDARG00000008859
danio_rerio	mylipb	ENSDARG00000055118
mus_musculus	Mylip	ENSMUSG00000038175
rattus_norvegicus	Mylip	ENSRNOG00000017579
drosophila_melanogaster	dnr1	FBGN0260866

Paralogs (10): EPB41L2 (ENSG00000079819), EPB41L3 (ENSG00000082397), EPB41L1 (ENSG00000088367), EPB41L4B (ENSG00000095203), EPB41L5 (ENSG00000115109), EPB41L4A (ENSG00000129595), FRMD6 (ENSG00000139926), EPB41 (ENSG00000159023), FRMD5 (ENSG00000171877), FRMD3 (ENSG00000172159)

Protein

Protein identifiers

E3 ubiquitin-protein ligase MYLIP — Q8WY64 (reviewed: Q8WY64)

Alternative names: Inducible degrader of the LDL-receptor, Myosin regulatory light chain interacting protein, RING-type E3 ubiquitin transferase MYLIP

All UniProt accessions (2): Q8WY64, Q5TIA5

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.

Subunit / interactions. Homodimer. Interacts with the E2 ubiquitin-conjugating enzyme, UBE2D1 (via RING-type zinc finger). Interacts with myosin regulatory light chain (MRLC) and TMEM4.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Autoubiquitinated.

Activity regulation. Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity.

Domain organisation. The RING domain mediates ubiquitination and the neurite outgrowth inhibitory activity. The FERM domain binds phospholipids and mediates lipoprotein receptors recognition at the plasma membrane through their cytoplasmic tails. The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes.

Induction. Expression is directly activated by NR1H2 and NR1H3. Expression is not dependent of the sterol-response element-binding proteins (SREBPs). Expression is indirectly induced by LDL.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WY64-1	1	yes
Q8WY64-2	2

RefSeq proteins (1): NP_037394* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000798	Ez/rad/moesin-like	Family
IPR001841	Znf_RING	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR041790	MYLIP_FERM_C	Domain

Pfam: PF00373, PF09379, PF09380, PF13920

UniProt features (59 total): strand 18, helix 14, turn 8, mutagenesis site 6, sequence conflict 3, binding site 3, splice variant 2, chain 1, domain 1, zinc finger region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9SA1	X-RAY DIFFRACTION	1.06
9SA2	X-RAY DIFFRACTION	1.1
13SY	X-RAY DIFFRACTION	1.29
13SQ	X-RAY DIFFRACTION	1.3
13SL	X-RAY DIFFRACTION	1.34
13SX	X-RAY DIFFRACTION	1.36
13ST	X-RAY DIFFRACTION	1.37
13SW	X-RAY DIFFRACTION	1.37
13SM	X-RAY DIFFRACTION	1.4
13SE	X-RAY DIFFRACTION	1.44
13SN	X-RAY DIFFRACTION	1.44
13SJ	X-RAY DIFFRACTION	1.47
13SC	X-RAY DIFFRACTION	1.48
13SB	X-RAY DIFFRACTION	1.48
13SZ	X-RAY DIFFRACTION	1.49
13SU	X-RAY DIFFRACTION	1.5
13TA	X-RAY DIFFRACTION	1.51
13SD	X-RAY DIFFRACTION	1.52
13SK	X-RAY DIFFRACTION	1.54
13SI	X-RAY DIFFRACTION	1.54
13TB	X-RAY DIFFRACTION	1.55
13SA	X-RAY DIFFRACTION	1.57
13SH	X-RAY DIFFRACTION	1.6
13SO	X-RAY DIFFRACTION	1.61
13SR	X-RAY DIFFRACTION	1.65
13RZ	X-RAY DIFFRACTION	1.66
13SV	X-RAY DIFFRACTION	1.68
13SS	X-RAY DIFFRACTION	1.69
13SP	X-RAY DIFFRACTION	1.69
13SF	X-RAY DIFFRACTION	1.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WY64-F1	86.16	0.63

Functional residue map

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

Ligand- & substrate-binding residues (3): 360; 363; 368

Mutagenesis-validated functional residues (6):

Position	Phenotype
265	unable to clear ldlr from the plasma membrane.
269	unable to clear ldlr from the plasma membrane.
387	abolishes autoubiquitination.
387	abolishes ubiquitin ligase activity.
389	inhibits ldlr degradation.
415	inhibits ldlr degradation.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-8866427	VLDLR internalisation and degradation
R-HSA-9031525	NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8964043	Plasma lipoprotein clearance
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 348 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_STEROL_HOMEOSTASIS, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, PEREZ_TP63_TARGETS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_493, GOBP_NEUROGENESIS, GOBP_LOW_DENSITY_LIPOPROTEIN_PARTICLE_CLEARANCE, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_LIPID_HOMEOSTASIS, GGGCATT_MIR365, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (9): ubiquitin-dependent protein catabolic process (GO:0006511), nervous system development (GO:0007399), negative regulation of neuron projection development (GO:0010977), negative regulation of low-density lipoprotein particle clearance (GO:0010989), protein ubiquitination (GO:0016567), protein destabilization (GO:0031648), regulation of low-density lipoprotein particle receptor catabolic process (GO:0032803), cholesterol homeostasis (GO:0042632), positive regulation of protein catabolic process (GO:0045732)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), cytoskeletal protein binding (GO:0008092), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Plasma lipoprotein clearance	1
NR1H2 and NR1H3-mediated signaling	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1
Signal Transduction	1
Signaling by Nuclear Receptors	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of protein catabolic process	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
system development	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
protein modification by small protein conjugation	1
regulation of protein stability	1
low-density lipoprotein particle receptor catabolic process	1
regulation of receptor catabolic process	1
sterol homeostasis	1
positive regulation of catabolic process	1
protein catabolic process	1
positive regulation of protein metabolic process	1
ubiquitin-like protein transferase activity	1
protein binding	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYLIP	XPR1	Q9UBH6	896
MYLIP	CNPY2	Q9Y2B0	848
MYLIP	ABCA1	O95477	809
MYLIP	MYL11	Q96A32	760
MYLIP	ABCG1	P45844	741
MYLIP	CYP7A1	P22680	715
MYLIP	SREBF2	Q12772	709
MYLIP	PSAP	P07292	693
MYLIP	HMGCR	P04035	685
MYLIP	MYL12B	O14950	684
MYLIP	PSAPL1	Q6NUJ1	674
MYLIP	ABCG5	Q9H222	649
MYLIP	PCSK9	Q8NBP7	648
MYLIP	NR1H4	Q96RI1	611
MYLIP	ABCG8	Q9H221	606

IntAct

135 interactions, top by confidence:

A	B	Type	Score
TSC1	MYLIP	psi-mi:“MI:0915”(physical association)	0.720
MYLIP	RASSF5	psi-mi:“MI:0915”(physical association)	0.670
RASSF5	MYLIP	psi-mi:“MI:0915”(physical association)	0.670
MYLIP	LNX2	psi-mi:“MI:0915”(physical association)	0.670
LNX2	MYLIP	psi-mi:“MI:0915”(physical association)	0.670
MIPOL1	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
TSC22D4	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
MYLIP	MIPOL1	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
EFHC2	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
KANK4	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
MYLIP	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
MYLIP	HOOK2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB16	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
MYLIP	INO80B	psi-mi:“MI:0915”(physical association)	0.560
MYLIP	ZBTB18	psi-mi:“MI:0915”(physical association)	0.560
PAX9	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
NR1D2	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
ZBTB42	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	MYLIP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (85): TSC22D4 (Two-hybrid), RASSF5 (Two-hybrid), MIPOL1 (Two-hybrid), MYLIP (Synthetic Lethality), MYLIP (Two-hybrid), MYLIP (Two-hybrid), MYLIP (Biochemical Activity), MYLIP (Two-hybrid), MYLIP (Affinity Capture-Western), MYLIP (Affinity Capture-Western), LDLR (Co-localization), CTR9 (Affinity Capture-MS), WDFY1 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), PAF1 (Affinity Capture-MS)

ESM2 similar proteins: A2ALK8, A8XWC4, D3ZDI6, F1LYQ8, F1M386, F1MSG6, F1P065, F1PBJ0, F8VPU2, G5EDB9, O14936, O35239, O70589, O94887, P26045, P28191, P43378, P54936, P70600, P97874, Q05397, Q05AK5, Q14289, Q14644, Q15283, Q28013, Q3UYK3, Q4KWH5, Q4KWH8, Q58CU2, Q5RAB8, Q60790, Q62915, Q641Z2, Q6NVF0, Q6P7F1, Q6TEM9, Q8BM54, Q8CHG7, Q8TEU7

Diamond homologs: A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863, O10296, O10324, O14064, O15392, O62640, O70201, O88738, P40629, P41435, P41436, P41437, P41454, P47732, P98170, Q05AK5, Q0WPJ7, Q13489, Q13490, Q28ER3, Q28H51, Q50L39, Q557E7, Q5BKL8, Q5R881, Q5RAH9, Q60989, Q62210, Q69Z36, Q6I6F4, Q6J1J1, Q6NTT6

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MYLIP	ubiquitination
MYLIP	“down-regulates quantity by destabilization”	LDLR	ubiquitination
MYLIP	“down-regulates quantity by destabilization”	LRP8	ubiquitination
MYLIP	“down-regulates quantity by destabilization”	VLDLR	ubiquitination
MYLIP	“down-regulates quantity”	AR	ubiquitination
MYLIP	“down-regulates quantity by destabilization”	MYLIP	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	38
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

666 predictions. Top by Δscore:

Variant	Effect	Δscore
6:16129407:CAGGT:C	donor_loss	1.0000
6:16129410:GTGAG:G	donor_loss	1.0000
6:16129411:T:A	donor_loss	1.0000
6:16141620:TGCA:T	acceptor_loss	1.0000
6:16141621:GCA:G	acceptor_loss	1.0000
6:16141622:CA:C	acceptor_loss	1.0000
6:16141623:A:AG	acceptor_gain	1.0000
6:16141624:G:C	acceptor_loss	1.0000
6:16141624:G:GA	acceptor_gain	1.0000
6:16141624:GGC:G	acceptor_gain	1.0000
6:16141624:GGCA:G	acceptor_gain	1.0000
6:16141624:GGCAT:G	acceptor_gain	1.0000
6:16141807:ACAGG:A	donor_loss	1.0000
6:16141808:CAGG:C	donor_loss	1.0000
6:16141810:GGT:G	donor_loss	1.0000
6:16141811:GTGA:G	donor_loss	1.0000
6:16141812:T:A	donor_loss	1.0000
6:16143007:T:A	acceptor_gain	1.0000
6:16143008:G:A	acceptor_gain	1.0000
6:16143010:T:TA	acceptor_gain	1.0000
6:16143017:CAG:C	acceptor_loss	1.0000
6:16143018:A:AG	acceptor_gain	1.0000
6:16143018:AGC:A	acceptor_loss	1.0000
6:16143019:G:GA	acceptor_gain	1.0000
6:16143019:GC:G	acceptor_gain	1.0000
6:16143019:GCA:G	acceptor_gain	1.0000
6:16143019:GCAT:G	acceptor_gain	1.0000
6:16143019:GCATT:G	acceptor_gain	1.0000
6:16143214:ATAGG:A	donor_loss	1.0000
6:16143215:TAGG:T	donor_loss	1.0000

AlphaMissense

2936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:16130632:T:A	W55R	1.000
6:16130632:T:C	W55R	1.000
6:16130645:G:T	R59I	1.000
6:16143833:G:C	R266P	1.000
6:16143856:T:C	F274L	1.000
6:16143858:C:A	F274L	1.000
6:16143858:C:G	F274L	1.000
6:16145006:T:C	F313L	1.000
6:16145008:T:A	F313L	1.000
6:16145008:T:G	F313L	1.000
6:16129390:G:A	G23D	0.999
6:16129402:T:C	L27P	0.999
6:16130596:G:A	G43R	0.999
6:16130596:G:C	G43R	0.999
6:16130597:G:A	G43E	0.999
6:16130600:T:C	L44P	0.999
6:16130634:G:C	W55C	0.999
6:16130634:G:T	W55C	0.999
6:16130636:T:C	L56P	0.999
6:16130640:C:A	N57K	0.999
6:16130640:C:G	N57K	0.999
6:16130645:G:C	R59T	0.999
6:16130646:A:C	R59S	0.999
6:16130646:A:T	R59S	0.999
6:16130704:A:G	K79E	0.999
6:16130706:G:C	K79N	0.999
6:16130706:G:T	K79N	0.999
6:16130707:T:C	F80L	0.999
6:16130709:C:A	F80L	0.999
6:16130709:C:G	F80L	0.999

dbSNP variants (sampled 300 via entrez): RS1000009635 (6:16147008 A>G), RS1000117315 (6:16150136 G>A), RS1000158893 (6:16149810 G>A), RS1000195873 (6:16148740 C>T), RS1000219487 (6:16144153 G>A), RS1000271536 (6:16144460 G>A,C), RS1000371089 (6:16131297 T>C), RS1000441656 (6:16130784 C>T), RS1000444000 (6:16138768 T>C), RS1000479330 (6:16149891 G>A), RS1000556613 (6:16145432 C>G,T), RS1000586137 (6:16161524 G>A), RS1000610775 (6:16145665 C>T), RS1000683425 (6:16144484 A>C,T), RS1000769979 (6:16132460 A>G)

Disease associations

OMIM: gene MIM:610082 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): inherited lipid metabolism disorder (MONDO:0002525)

Orphanet (1): Disorder of lipid metabolism (Orphanet:309005)

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000759_12	LDL cholesterol	1.000000e-11
GCST000760_17	Cholesterol, total	3.000000e-09
GCST000807_11	LDL cholesterol	2.000000e-08
GCST001408_5	Response to statins (LDL cholesterol change)	5.000000e-07
GCST001850_8	Major depressive disorder	1.000000e-06
GCST002221_69	Cholesterol, total	2.000000e-15
GCST002222_6	LDL cholesterol	2.000000e-17
GCST002875_140	Diisocyanate-induced asthma	1.000000e-06
GCST002898_23	LDL cholesterol	2.000000e-09
GCST004233_54	LDL cholesterol levels	8.000000e-17
GCST004235_32	Total cholesterol levels	8.000000e-13
GCST006445_8	Femoral neck bone mineral density	9.000000e-06
GCST007100_3	Asthma exacerbations in inhaled corticosteroid treatment	7.000000e-06
GCST007100_5	Asthma exacerbations in inhaled corticosteroid treatment	3.000000e-06
GCST007931_45	Medication use (HMG CoA reductase inhibitors)	4.000000e-10
GCST008077_15	LDL cholesterol levels	1.000000e-10
GCST008077_71	LDL cholesterol levels	6.000000e-09
GCST008078_151	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-29
GCST008078_64	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-25
GCST008079_5	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-30
GCST008079_51	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-26
GCST008086_26	LDL cholesterol levels in current drinkers	1.000000e-13
GCST008086_37	LDL cholesterol levels in current drinkers	4.000000e-15
GCST010243_162	Apolipoprotein B levels	8.000000e-24
GCST010245_130	LDL cholesterol levels	5.000000e-25

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0006995	response to diisocyanate
EFO:0007785	femoral neck bone mineral density
EFO:0007614	asthma exacerbation measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9370867	Efficacy	3	atorvastatin	Hypercholesterolemia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9370867	MYLIP	3	2.50	1	atorvastatin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	8
Benzo(a)pyrene	increases expression, increases methylation	4
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
potassium chromate(VI)	affects cotreatment, increases expression	2
chromium hexavalent ion	increases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Arsenic	decreases response to substance, affects cotreatment, decreases expression, increases abundance	2
Copper	decreases expression, increases expression, affects binding	2
Formaldehyde	increases expression	2
Lead	affects expression	2
Progesterone	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium bichromate	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
afimoxifene	decreases expression	1
zinc chromate	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00125125	PHASE4	COMPLETED	Fluvastatin in Adults With Dislipidemia With History of Muscle Problems
NCT00150384	PHASE4	COMPLETED	Clinical Utility of Caduet in Achieving Blood Pressure and Lipid Endpoints in a Specific Patient Population
NCT00171262	PHASE4	COMPLETED	Trial to Evaluate the Efficacy of Fluvastatin on Certain Markers
NCT00171327	PHASE4	COMPLETED	Efficacy and Safety of Fluvastatin or Valsartan and Their Combination in Dyslipidemic Patients With Hypertension and Endothelial Dysfunction
NCT00192621	PHASE4	COMPLETED	Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT00194402	PHASE4	COMPLETED	SLIM: Combined Effects of Slo-Niacin and Atorvastatin on Lipoproteins and Inflammatory Markers in Hyperlipidemia
NCT00249938	PHASE4	COMPLETED	Evaluation of Combination Cholesterol Treatments in Patients With High Cholesterol.
NCT00264394	PHASE4	COMPLETED	Cardiovascular Risk Factor Management in HIV Infection
NCT00282659	PHASE4	COMPLETED	The Use of Magnesium to Improve Blood Pressure, Cholesterol, and Glucose Control
NCT00330980	PHASE4	COMPLETED	Effects of Statin Medications on Mental Processes, Behavior, and Serotonin Levels
NCT00332761	PHASE4	COMPLETED	Caduet in an Untreated Subject Population
NCT00345657	PHASE4	COMPLETED	Efficacy Study of Extended-Release Niacin/Lovastatin Versus Usual Care
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00350038	PHASE4	COMPLETED	Irbesartan, Ciprofibrate and Their Combination Onto the Endothelial Functions
NCT00385658	PHASE4	COMPLETED	Efficacy of Fluvastatin and Fenofibrate in Comparison to Simvastatin and Ezetimibe in Patients With Metabolic Syndrome
NCT00412113	PHASE4	COMPLETED	A Multi-Risk Factor Strategy vs a Guideline-Based Approach in Achieving Blood Pressure and Lipid Goals in Hypertensives at Extra Risk
NCT00441480	PHASE4	COMPLETED	Effect of Plant Sterols Esterified to Fish Oil Fatty Acids on Plasma Lipid Levels
NCT00442325	PHASE4	COMPLETED	Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets
NCT00442845	PHASE4	COMPLETED	Establish The Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets (ACTFAST)
NCT00447070	PHASE4	COMPLETED	Effect of Atazanavir on Endothelial Function in HIV-Infected Patients
NCT00506961	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Rosuvastatin Versus Simvastatin in Type 2 Diabetic Patients With Dyslipidemia
NCT00540293	PHASE4	COMPLETED	Lipitor Korean Atorvastatin Goal Achievement Across Risk Levels Study
NCT00541554	PHASE4	UNKNOWN	Reversal of Antipsychotic-Induced Hyperprolactinemia, Weight Gain, Hyperglycemia and Dyslipidemia
NCT00644670	PHASE4	COMPLETED	A Study Of The Efficacy Of Atorvastatin For Lowering Cholesterol In High-Risk Patients With High Cholesterol
NCT00644709	PHASE4	COMPLETED	A Study Of Atorvastatin For The Treatment Of High Cholesterol In Patients At High Risk Of Coronary Heart Disease (CHD)
NCT00645151	PHASE4	COMPLETED	A Study Of The Efficacy Of Atorvastatin In Lowering Cholesterol In Latin American Patients With High Cholesterol
NCT00647543	PHASE4	COMPLETED	Atorvastatin Study For The Treatment Of High Cholesterol In Patients From Thailand
NCT00651963	PHASE4	COMPLETED	Open Label Study Evaluating The Use Of Combination Therapy Of Ezetimibe And Statins In Patients With Dyslipidemia In Colombia (0653-141)(COMPLETED)
NCT00665834	PHASE4	COMPLETED	Comparison of Rosuvastatin and Atorvastatin in Patients With Acute Coronary Syndrome
NCT00678743	PHASE4	COMPLETED	An Open-label Extension to Assess the Continued Efficacy of Omacor Plus Simvastatin
NCT00700037	PHASE4	COMPLETED	Change in Plaque Characteristics With Atorvastatin
NCT00708370	PHASE4	COMPLETED	A Study to Evaluate the Efficacy of a Counselling and Advisory Care for Health (COACH) Program in Dyslipidemic Patients.
NCT00712049	PHASE4	UNKNOWN	Effects of Nicotinic Acid Plus Simvastatin Versus Simvastatin Alone on Carotid and Femoral Intima-Media Thickness in Patients With Peripheral Artery Disease (NASCIT)
NCT01010516	PHASE4	UNKNOWN	Comparison of High-Dose Rosuvastatin Versus Low Statin Dose Plus Fenofibrate Versus Low Statin Dose Plus Niacin in the Treatment of Mixed Hyperlipidemia
NCT01025492	PHASE4	TERMINATED	Study of Trilipix Effects on Lipids and Arteries
NCT01029522	PHASE4	COMPLETED	Dyslipidemia in Cardiovascular Disease
NCT01052311	PHASE4	TERMINATED	The Impact of Tredaptive on Flow-Mediated Dilation in Cardiac Patients
NCT01239004	PHASE4	COMPLETED	Colesevelam Treatment for Impaired Fasting Glucose During Niacin Therapy
NCT01256476	PHASE4	COMPLETED	Prevail-Us: A Study Of Pitavastatin 4 mg Vs. Pravastatin 40 mg In Patients With Primary Hyperlipidemia Or Mixed Dyslipidemia