CHLSN

gene
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Also known as MGC11257YCR016W

Summary

CHLSN (cholesin, HGNC:22421) is a protein-coding gene on chromosome 7p22.3, encoding Protein cholesin (Q9BRJ6). Hormone secreted from the intestine in response to cholesterol, where it acts to inhibit cholesterol synthesis in the liver and VLDL secretion,leading to a reduction in circulating cholesterol levels.

Enables hormone activity. Involved in negative regulation of cholesterol biosynthetic process. Is active in extracellular space.

Source: NCBI Gene 84310 — RefSeq curated summary.

At a glance

  • GWAS associations: 17
  • Clinical variants (ClinVar): 221 total
  • Druggable target: yes
  • MANE Select transcript: NM_001318252

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:22421
Approved symbolCHLSN
Namecholesin
Location7p22.3
Locus typegene with protein product
StatusApproved
AliasesMGC11257, YCR016W
Ensembl geneENSG00000146540
Ensembl biotypeprotein_coding
OMIM621174
Entrez84310

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000357429, ENST00000397098, ENST00000397100, ENST00000412051, ENST00000444428, ENST00000465681, ENST00000488073, ENST00000491163, ENST00000853130, ENST00000853131

RefSeq mRNA: 11 — MANE Select: NM_001318252 NM_001134395, NM_001134396, NM_001318252, NM_001350968, NM_001350969, NM_001424325, NM_001424326, NM_001424327, NM_001424329, NM_001424333, NM_032350

CCDS: CCDS5320

Canonical transcript exons

ENST00000397098 — 5 exons

ExonStartEnd
ENSE0000103488811272571127386
ENSE00001527278997006997804
ENSE0000156416711373151138247
ENSE0000345900610004701000551
ENSE0000357312810099501010143

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.9860 / max 243.8719, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
8240132.84811810
8240320.82451764
824004.35391569
824021.9595923

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
adenohypophysisUBERON:000219698.18gold quality
right coronary arteryUBERON:000162597.24gold quality
pituitary glandUBERON:000000796.85gold quality
anterior cingulate cortexUBERON:000983596.71gold quality
right frontal lobeUBERON:000281096.68gold quality
amygdalaUBERON:000187696.62gold quality
apex of heartUBERON:000209896.49gold quality
sural nerveUBERON:001548896.49gold quality
popliteal arteryUBERON:000225096.28gold quality
tibial arteryUBERON:000761096.27gold quality
Brodmann (1909) area 9UBERON:001354096.21gold quality
putamenUBERON:000187495.87gold quality
nucleus accumbensUBERON:000188295.74gold quality
tibial nerveUBERON:000132395.70gold quality
aortaUBERON:000094795.65gold quality
body of pancreasUBERON:000115095.61gold quality
mucosa of stomachUBERON:000119995.52gold quality
descending thoracic aortaUBERON:000234595.50gold quality
right lobe of thyroid glandUBERON:000111995.45gold quality
C1 segment of cervical spinal cordUBERON:000646995.44gold quality
left coronary arteryUBERON:000162695.42gold quality
left lobe of thyroid glandUBERON:000112095.27gold quality
right atrium auricular regionUBERON:000663195.15gold quality
ascending aortaUBERON:000149695.09gold quality
caudate nucleusUBERON:000187395.09gold quality
hypothalamusUBERON:000189895.09gold quality
thoracic aortaUBERON:000151595.03gold quality
coronary arteryUBERON:000162194.96gold quality
prefrontal cortexUBERON:000045194.95gold quality
lower esophagus muscularis layerUBERON:003583394.89gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-HCAD-4yes57.15
E-ANND-3yes11.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-76599.8468.242442
HSA-MIR-11181-3P99.7566.382205
HSA-MIR-520F-5P99.3470.401632
HSA-MIR-3675-3P99.0967.70968
HSA-MIR-1301-3P98.6468.271071
HSA-MIR-7156-3P98.2567.66859
HSA-MIR-4691-3P98.1166.831204
HSA-MIR-3173-5P97.3565.821282
HSA-MIR-6799-3P97.3565.601302
HSA-MIR-6742-5P96.3264.01869
HSA-MIR-393787.6961.61103

Literature-anchored findings (GeneRIF, showing 2)

  • Three ubiquitous methylation loci were consistently and strongly associated with type 2 diabetes in Ghanaians: TXNIP, C7orf50 and CPT1A (PMID:30107520)
  • A gut-derived hormone regulates cholesterol metabolism. (PMID:38503280)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriozmp:0000000624ENSDARG00000045254
mus_musculusChlsnENSMUSG00000053553
rattus_norvegicusC12h7orf50ENSRNOG00000001289

Protein

Protein identifiers

Protein cholesinQ9BRJ6 (reviewed: Q9BRJ6)

All UniProt accessions (4): Q9BRJ6, C9JQV0, H7C0T1, H7C2R9

UniProt curated annotations — full annotation on UniProt →

Function. Hormone secreted from the intestine in response to cholesterol, where it acts to inhibit cholesterol synthesis in the liver and VLDL secretion,leading to a reduction in circulating cholesterol levels. Acts through binding to its receptor, GPR146.

Subcellular location. Secreted.

Tissue specificity. Secreted from the instestine, secretion is induced by feeding and cholesterol absorption.

Induction. Expression is induced by feeding and cholesterol absorption.

RefSeq proteins (12): NP_001127867, NP_001127868, NP_001305181, NP_001337897, NP_001337898, NP_001411254, NP_001411255, NP_001411256, NP_001411258, NP_001411262, NP_001411263, NP_115726 (=MANE)

Domains & families (InterPro)

IDNameType
IPR019327WKFDomain

Pfam: PF10180

UniProt features (7 total): modified residue 4, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BRJ6-F175.360.47

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 (4): 23, 59, 97, 175

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ALCOHOL_BIOSYNTHETIC_PROCESS, chr7p22, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CHOLESTEROL_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, KOYAMA_SEMA3B_TARGETS_UP, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, ZHU_CMV_ALL_DN, GOBP_REGULATION_OF_STEROID_BIOSYNTHETIC_PROCESS

GO Biological Process (4): negative regulation of cholesterol biosynthetic process (GO:0045541), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), regulation of cholesterol biosynthetic process (GO:0045540), positive regulation of cholesterol biosynthetic process (GO:0045542)

GO Molecular Function (3): RNA binding (GO:0003723), hormone activity (GO:0005179), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cholesterol biosynthetic process3
regulation of cholesterol biosynthetic process2
negative regulation of cholesterol metabolic process1
negative regulation of sterol biosynthetic process1
negative regulation of alcohol biosynthetic process1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway1
adenylate cyclase inhibitor activity1
regulation of cholesterol metabolic process1
regulation of sterol biosynthetic process1
regulation of alcohol biosynthetic process1
positive regulation of cholesterol metabolic process1
positive regulation of sterol biosynthetic process1
positive regulation of alcohol biosynthetic process1
nucleic acid binding1
receptor ligand activity1
binding1
cellular anatomical structure1

Protein interactions and networks

STRING

1260 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CHLSNMAK16Q9BXY0490
CHLSNCFAP74Q9C0B2468
CHLSNTMA16Q96EY4466
CHLSNSLC22A23A1A5C7449
CHLSNGOLGA8CPA6NN73419
CHLSNZNF705AQ6ZN79418
CHLSNEME2A4GXA9416
CHLSNRNGTTO60942374
CHLSNGOLGA6L6A8MZA4368
CHLSNZAR1Q86SH2365
CHLSNMYO19Q96H55359
CHLSNGOLGA6L1Q8N7Z2358
CHLSNSTON2Q8WXE9355
CHLSNGALNT9Q9HCQ5349
CHLSNRASA3Q14644348

IntAct

176 interactions, top by confidence:

ABTypeScore
CHLSNTHAP1psi-mi:“MI:0915”(physical association)0.720
THAP1CHLSNpsi-mi:“MI:0915”(physical association)0.720
PTK2TGFB1I1psi-mi:“MI:0914”(association)0.680
LIN28AIGF2BP3psi-mi:“MI:0914”(association)0.640
NPM1MPHOSPH10psi-mi:“MI:0914”(association)0.610
GRNCHLSNpsi-mi:“MI:0915”(physical association)0.560
CHLSNWFS1psi-mi:“MI:0915”(physical association)0.560
HTTCHLSNpsi-mi:“MI:0915”(physical association)0.560
RPL28MAGEB2psi-mi:“MI:0914”(association)0.560
CHLSNRPL14psi-mi:“MI:0914”(association)0.530
RPL37AMPHOSPH10psi-mi:“MI:0914”(association)0.530
ZC3HAV1KHNYNpsi-mi:“MI:0914”(association)0.530
RPL30RRP8psi-mi:“MI:0914”(association)0.530
MAGEB2GTPBP10psi-mi:“MI:0914”(association)0.530
CHLSNtaxpsi-mi:“MI:0915”(physical association)0.490
taxCHLSNpsi-mi:“MI:0915”(physical association)0.490
H3C1SMCHD1psi-mi:“MI:2364”(proximity)0.410
CHLSNALDH1B1psi-mi:“MI:0915”(physical association)0.400
GNAT3psi-mi:“MI:0915”(physical association)0.400

BioGRID (218): C7orf50 (Two-hybrid), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Two-hybrid), C7orf50 (Affinity Capture-MS), C7orf50 (Reconstituted Complex), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS), C7orf50 (Affinity Capture-MS)

ESM2 similar proteins: B0K019, B2KF05, D3ZQL6, D4A615, D4ACP5, E1BBG2, O15037, O43159, O94762, P46087, Q07G43, Q15477, Q4KLL9, Q5REG4, Q5T124, Q5TKR9, Q5U4F0, Q5ZLK6, Q60739, Q6AXX1, Q6NZL6, Q6NZR5, Q6PFD6, Q6ZQF7, Q7L2J0, Q80U38, Q80V91, Q8BGT6, Q8BHW9, Q8BZ21, Q8C0J6, Q8C2K5, Q8CFK6, Q8IV53, Q8IY33, Q8K1S6, Q8K3A9, Q8N3F8, Q8N9I9, Q8TE77

Diamond homologs: Q5I0E3, Q9BRJ6, Q9CXL3

SIGNOR signaling

1 interactions.

AEffectBMechanism
SMURF1unknownC7orf50ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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:

PathwayPartnersFoldFDR
Peptide chain elongation2120.7×2e-20
Viral mRNA Translation2120.7×2e-20
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA2120.4×2e-20
Selenocysteine synthesis2119.6×5e-20
Eukaryotic Translation Termination2119.6×5e-20
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)2119.2×6e-20
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA2119.2×6e-20
Formation of a pool of free 40S subunits2219.1×2e-20

GO biological processes:

GO termPartnersFoldFDR
cytoplasmic translation2223.4×2e-21
ribosomal large subunit biogenesis717.8×2e-05
translation2313.6×5e-17
ribosomal small subunit biogenesis1013.1×1e-06
rRNA processing1411.4×8e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance178
Likely benign18
Benign7

Top pathogenic / likely-pathogenic (0)

SpliceAI

4199 predictions. Top by Δscore:

VariantEffectΔscore
7:1000547:CCCAT:Cacceptor_gain1.0000
7:1000548:CCAT:Cacceptor_gain1.0000
7:1000548:CCATC:Cacceptor_gain1.0000
7:1000549:CAT:Cacceptor_gain1.0000
7:1000549:CATC:Cacceptor_gain1.0000
7:1000552:C:CCacceptor_gain1.0000
7:1055481:AAGGT:Adonor_loss1.0000
7:1055482:AGGTG:Adonor_loss1.0000
7:1055484:GT:Gdonor_loss1.0000
7:1127251:CCTTA:Cdonor_loss1.0000
7:1127252:CTTAC:Cdonor_loss1.0000
7:1127253:TTA:Tdonor_loss1.0000
7:1127254:TA:Tdonor_loss1.0000
7:1127255:A:ACdonor_gain1.0000
7:1127255:A:AGdonor_loss1.0000
7:1127256:C:CCdonor_gain1.0000
7:1127382:CCATC:Cacceptor_gain1.0000
7:1127383:CATC:Cacceptor_gain1.0000
7:1127383:CATCC:Cacceptor_gain1.0000
7:1127384:ATC:Aacceptor_gain1.0000
7:1127385:TC:Tacceptor_gain1.0000
7:1127386:CC:Cacceptor_gain1.0000
7:1127386:CCTGC:Cacceptor_loss1.0000
7:1127387:C:CCacceptor_gain1.0000
7:1127387:C:CGacceptor_loss1.0000
7:1127388:T:Cacceptor_loss1.0000
7:1127393:C:CTacceptor_gain1.0000
7:997803:ACCTG:Aacceptor_loss1.0000
7:997806:T:Aacceptor_loss1.0000
7:1000465:CACA:Cdonor_loss0.9900

AlphaMissense

1232 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:1000521:A:CF118L0.998
7:1000521:A:TF118L0.998
7:1000523:A:GF118L0.998
7:1000522:A:GF118S0.991
7:1000522:A:CF118C0.987
7:1000527:C:AW116C0.986
7:1000527:C:GW116C0.986
7:997787:G:CF141L0.986
7:997787:G:TF141L0.986
7:997789:A:GF141L0.986
7:1000498:A:TL126H0.983
7:1000529:A:GW116R0.981
7:1000529:A:TW116R0.981
7:1000523:A:CF118V0.979
7:997767:A:GL148P0.979
7:1000515:C:AK120N0.978
7:1000515:C:GK120N0.978
7:997803:A:TV136D0.978
7:1000498:A:GL126P0.977
7:997723:C:GA163P0.977
7:997771:A:CY147D0.977
7:1000523:A:TF118I0.975
7:1000506:C:AQ123H0.973
7:1000506:C:GQ123H0.973
7:1000495:A:GL127P0.971
7:1000502:A:GW125R0.971
7:1000502:A:TW125R0.971
7:997758:A:GL151P0.971
7:1000498:A:CL126R0.969
7:997771:A:GY147H0.969

dbSNP variants (sampled 300 via entrez): RS1000005933 (7:1007706 T>A,C), RS1000011906 (7:1096458 G>A,C), RS1000046278 (7:1095532 C>T), RS1000090736 (7:1092673 C>T), RS1000090921 (7:1125086 G>A), RS1000095024 (7:1029555 C>T), RS1000099848 (7:1063601 G>A), RS1000105732 (7:978523 A>G), RS1000160165 (7:994418 C>A,G,T), RS1000172939 (7:1053060 G>T), RS1000174950 (7:979315 G>A), RS1000249512 (7:1070863 C>T), RS1000250523 (7:1021909 A>C), RS1000254419 (7:979290 C>T), RS1000257716 (7:1099195 G>A)

Disease associations

OMIM: gene MIM:621174 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

StudyTraitp-value
GCST000785_22Longevity1.000000e-06
GCST003678_19C-reactive protein levels or total cholesterol levels (pleiotropy)3.000000e-09
GCST003819_2Endometriosis3.000000e-06
GCST006612_32LDL cholesterol2.000000e-16
GCST006614_134Total cholesterol levels8.000000e-19
GCST008084_165HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)2.000000e-08
GCST008084_93HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)1.000000e-08
GCST010204_188Low density lipoprotein cholesterol levels6.000000e-12
GCST010242_139HDL cholesterol levels2.000000e-12
GCST010242_291HDL cholesterol levels3.000000e-26
GCST010245_81LDL cholesterol levels1.000000e-08
GCST012489_75Heel bone mineral density x serum urate levels interaction4.000000e-09
GCST90002385_174High light scatter reticulocyte count2.000000e-16
GCST90002392_710Mean corpuscular volume5.000000e-12
GCST90002397_496Mean spheric corpuscular volume1.000000e-12
GCST90002405_215Reticulocyte count4.000000e-18
GCST90002406_234Reticulocyte fraction of red cells7.000000e-17

EFO canonical traits (8, from GWAS)

EFO IDTrait name
EFO:0004458C-reactive protein measurement
EFO:0004574total cholesterol measurement
EFO:0004611low density lipoprotein cholesterol measurement
EFO:0004329alcohol drinking
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0004531urate measurement
EFO:0009270heel bone mineral density
EFO:0007986reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066340 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.82Kd15.12nMCHEMBL3752910
7.82ED5015.12nMCHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2147974: Binding affinity to human C7orf50 incubated for 45 mins by Kinobead based pull down assaykd0.0151uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidincreases expression, increases methylation, affects expression5
bisphenol Aaffects methylation, decreases expression, decreases methylation, increases expression4
Benzo(a)pyrenedecreases expression, increases methylation3
sodium arsenitedecreases expression, increases expression2
Tobacco Smoke Pollutiondecreases methylation2
Aflatoxin B1increases methylation2
GSK-J4increases expression1
FR900359increases phosphorylation1
bisphenol Faffects cotreatment, increases methylation1
cobaltous chloridedecreases expression1
aflatoxin B2increases methylation1
cyclic 3’,5’-uridine monophosphateaffects binding1
di-n-butylphosphoric acidaffects expression1
K 7174decreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
ICG 001increases expression1
bisphenol Sdecreases methylation1
jinfukangincreases expression1
LDN 193189decreases expression, affects cotreatment1
(+)-JQ1 compounddecreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Fulvestrantaffects cotreatment, increases methylation1
Arsenicaffects expression1
Benzeneincreases expression1
Caffeineincreases phosphorylation1
Dimethyl Sulfoxideincreases expression1
Diurondecreases expression1
Enzyme Inhibitorsdecreases activity, increases O-linked glycosylation1
Ivermectindecreases expression1
Quercetindecreases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5651016BindingBinding affinity to human C7orf50 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): endometriosis