NPC1L1 (NPC1 like intracellular cholesterol transporter 1)

Gene

• Entrez ID: 29881
• Gene name: NPC1 like intracellular cholesterol transporter 1
• Gene symbol: NPC1L1
• Synonyms (NCBI Gene): LDLCQ7, NPC11L1, SLC65A2
• Chromosome: 7
• Chromosome location: 7p13
• Summary: The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi netw

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs52815063	A>T	Likely-benign, drug-response	Missense variant, genic downstream transcript variant, coding sequence variant
rs119457968	C>A,G,T	Drug-response	Non coding transcript variant, missense variant, coding sequence variant, 5 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1190524	hsa-miR-3612	CLIP-seq
MIRT1190525	hsa-miR-4459	CLIP-seq
MIRT1190526	hsa-miR-4695-5p	CLIP-seq
MIRT1190527	hsa-miR-650	CLIP-seq
MIRT1190528	hsa-miR-665	CLIP-seq
MIRT1190529	hsa-miR-765	CLIP-seq
MIRT1190530	hsa-miR-3074-5p	CLIP-seq
MIRT1190531	hsa-miR-3135	CLIP-seq
MIRT1190532	hsa-miR-3164	CLIP-seq
MIRT1190533	hsa-miR-3180-5p	CLIP-seq
MIRT1190524	hsa-miR-3612	CLIP-seq
MIRT1190534	hsa-miR-3922-5p	CLIP-seq
MIRT1190525	hsa-miR-4459	CLIP-seq
MIRT1190526	hsa-miR-4695-5p	CLIP-seq
MIRT1190535	hsa-miR-4722-3p	CLIP-seq
MIRT1190536	hsa-miR-520a-5p	CLIP-seq
MIRT1190537	hsa-miR-525-5p	CLIP-seq
MIRT1190527	hsa-miR-650	CLIP-seq
MIRT1190528	hsa-miR-665	CLIP-seq
MIRT1190529	hsa-miR-765	CLIP-seq
MIRT2055151	hsa-miR-1302	CLIP-seq
MIRT2055152	hsa-miR-1304	CLIP-seq
MIRT2055153	hsa-miR-3174	CLIP-seq
MIRT2055154	hsa-miR-3659	CLIP-seq
MIRT2055155	hsa-miR-4298	CLIP-seq
MIRT2055156	hsa-miR-450b-3p	CLIP-seq
MIRT2055157	hsa-miR-4648	CLIP-seq
MIRT2055158	hsa-miR-4654	CLIP-seq
MIRT2055159	hsa-miR-4658	CLIP-seq
MIRT2055160	hsa-miR-4713-3p	CLIP-seq
MIRT2055161	hsa-miR-4765	CLIP-seq
MIRT2055162	hsa-miR-4769-5p	CLIP-seq
MIRT2055163	hsa-miR-4802-3p	CLIP-seq
MIRT2055164	hsa-miR-574-5p	CLIP-seq
MIRT2055165	hsa-miR-638	CLIP-seq
MIRT2055166	hsa-miR-661	CLIP-seq
MIRT2055167	hsa-miR-769-3p	CLIP-seq
MIRT2055151	hsa-miR-1302	CLIP-seq
MIRT2055153	hsa-miR-3174	CLIP-seq
MIRT2055154	hsa-miR-3659	CLIP-seq
MIRT2055155	hsa-miR-4298	CLIP-seq
MIRT2055157	hsa-miR-4648	CLIP-seq
MIRT2055158	hsa-miR-4654	CLIP-seq
MIRT2055159	hsa-miR-4658	CLIP-seq
MIRT2055161	hsa-miR-4765	CLIP-seq
MIRT2055162	hsa-miR-4769-5p	CLIP-seq
MIRT2055163	hsa-miR-4802-3p	CLIP-seq
MIRT2055164	hsa-miR-574-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HNF4A	Activation	21123766
SREBF2	Activation	21123766
SREBF2	Unknown	20460578;21527728

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	19542231, 22095670, 24336247, 29880681
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	19325169, 24336247
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006695	Process	Cholesterol biosynthetic process	IMP	17140581
GO:0008202	Process	Steroid metabolic process	IEA
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0008431	Function	Vitamin E binding	IDA	28315682
GO:0015485	Function	Cholesterol binding	IBA
GO:0015485	Function	Cholesterol binding	IDA	21602275, 34407950
GO:0015485	Function	Cholesterol binding	IEA
GO:0015918	Process	Sterol transport	IBA
GO:0016020	Component	Membrane	IEA
GO:0016324	Component	Apical plasma membrane	IEA
GO:0030299	Process	Intestinal cholesterol absorption	IBA
GO:0030299	Process	Intestinal cholesterol absorption	IMP	17140581
GO:0030301	Process	Cholesterol transport	IEA
GO:0030301	Process	Cholesterol transport	IMP	17140581, 24336247
GO:0030659	Component	Cytoplasmic vesicle membrane	IEA
GO:0031267	Function	Small GTPase binding	IPI	19542231
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0031489	Function	Myosin V binding	IPI	19542231
GO:0042157	Process	Lipoprotein metabolic process	IMP	17140581
GO:0042360	Process	Vitamin E metabolic process	IDA	28315682
GO:0042632	Process	Cholesterol homeostasis	IBA
GO:0042803	Function	Protein homodimerization activity	IDA	34407950
GO:0051180	Process	Vitamin transport	IDA	18403720, 28315682
GO:0071501	Process	Cellular response to sterol depletion	IDA	19325169

Other IDs

• MIM: 608010
• HGNC: 7898
• e!Ensembl: ENSG00000015520

Protein

• UniProt ID: Q9UHC9
• Protein name: NPC1-like intracellular cholesterol transporter 1 (NPC1L1) (Niemann-Pick C1-like protein 1)
• Protein function: Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant sterol absorption, it transports sitosterol, alt
• PDB: 3QNT, 7DF8, 7DFW, 7DFZ, 7N4U, 7N4V, 7N4X
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16414	NPC1_N	30 → 283	Niemann-Pick C1 N terminus	Domain
  PF12349	Sterol-sensing	661 → 815	Sterol-sensing domain of SREBP cleavage-activation	Family
  PF02460	Patched	1087 → 1294	Patched family	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. Expressed in liver. Also expressed in small intestine, pancreas, kidney, lung, pancreas, spleen, heart, gall bladder, brain, testis, stomach and muscle. {ECO:0000269|PubMed:10783261, ECO:0000269|PubMed:14976318, ECO:0
• Sequence:

  MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSN
  TPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNF
  VNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAA
  ATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGV
  ARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTI
  LLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSV
  IPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSY
  RYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNT
  SLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALAL
  SCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEM
  RAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRV
  MVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLE
  YQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAV
  ILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFL
  LHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPV
  YFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDW
  LTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRP
  NIKCPKGGLAAYSTSVNLTSDGQVLDTVAILSPRLEYSGTISAHCNLYLLDSTSRFMAYH
  KPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGL
  FMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVS
  AVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQ
  LIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCP
  NHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF

• Sequence length: 1359

Pathways

KEGG:

Fat digestion and absorption

Reactome:

Intestinal lipid absorption

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CARDIOVASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ezetimibe response	drug response; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERLIPIDEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 7	Uncertain significance; association	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NPC1L1-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Statins, attenuated cholesterol lowering by	drug response; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arteriosclerosis	Arteriosclerosis	BEFREE	25261526, 31064810		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	25261526, 31064810		★☆☆☆☆ Found in Text Mining only
Atypical Ductal Breast Hyperplasia	Breast Hyperplasia	BEFREE	19747803		★☆☆☆☆ Found in Text Mining only
Cholecystolithiasis	Cholecystolithiasis	BEFREE	23406058, 26800364, 29764733		★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholelithiasis	BEFREE	23406058, 25841872, 26800364, 26859812, 29764733		★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholecystolithiasis	Pubtator	26800364, 29764733, 32366946	Associate	★☆☆☆☆ Found in Text Mining only
Cholesterol gallstones	Cholesterol gallstones	BEFREE	19071091, 21494140, 24525336, 26800364, 28627641		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	34511128	Stimulate	★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	25390462, 26253792, 26890452, 27701660, 30789754		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	25390462, 26890452, 27701660, 30326043, 30789754		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	26946290, 38233830	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Disease	Coronary artery disease	Pubtator	19752398, 25390462, 25770315, 26890452, 30789754, 34675202, 39358768	Associate	★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	19752398, 25390462, 25770315, 26477595, 26890452, 27701660, 29800275, 30326043, 30789754		★☆☆☆☆ Found in Text Mining only
Coronary Vessel Anomalies	Coronary vessel anomalies	Pubtator	38233830	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	23139223		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	31311377	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	40004948	Stimulate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	26859812, 27701660, 30326043		★☆☆☆☆ Found in Text Mining only
Diabetic Neuropathies	Diabetic neuropathy	Pubtator	40225015	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	40225015	Stimulate	★☆☆☆☆ Found in Text Mining only
Dyslipidemias	Dyslipidemias	BEFREE	24861377, 31064810		★☆☆☆☆ Found in Text Mining only
Familial hypobetalipoproteinemia	Hypobetalipoproteinemia	BEFREE	22155345		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	20809793		★☆☆☆☆ Found in Text Mining only
Fatty Liver, Alcoholic	Alcoholic Fatty Liver	BEFREE	31432115		★☆☆☆☆ Found in Text Mining only
Gallstones	Gallstones	Pubtator	20144195	Inhibit	★☆☆☆☆ Found in Text Mining only
Gallstones	Gallstones	Pubtator	26800364, 29764733	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	19752398		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	19752398	Associate	★☆☆☆☆ Found in Text Mining only
Hepatitis C	Hepatitis c	Pubtator	27769799	Associate	★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	LHGDN	15671032		★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	BEFREE	16083725, 20543520, 23139223, 24859282, 29601818, 30242108, 31590417		★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	Pubtator	36234807	Associate	★☆☆☆☆ Found in Text Mining only
Hyperlipidemia	Hyperlipidemia	BEFREE	23415434, 29601818, 31064810		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperlipoproteinemia Type IIa	Hyperlipoproteinemia	BEFREE	19747803		★☆☆☆☆ Found in Text Mining only
Hypocholesterolemia	Hypocholesterolemia	BEFREE	17008555		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	39358768	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	29483961		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	29186684		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29106532		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	20809793		★☆☆☆☆ Found in Text Mining only
Myocardial Ischemia	Myocardial Ischemia	BEFREE	26859812		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Familial hypobetalipoproteinemia	Hypobetalipoproteinemia	Orphanet			★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	25102981, 27923447, 29466845		★☆☆☆☆ Found in Text Mining only
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	BEFREE	27634173		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	18031309, 20809793		★☆☆☆☆ Found in Text Mining only
Sitosterolemia	Sitosterolemia	BEFREE	25056759		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	20809793, 28714405		★☆☆☆☆ Found in Text Mining only