CLPS

Summary

CLPS (colipase, HGNC:2085) is a protein-coding gene on chromosome 6p21.31, encoding Colipase (P04118). Colipase is a cofactor of pancreatic lipase.

The protein encoded by this gene is a cofactor needed by pancreatic lipase for efficient dietary lipid hydrolysis. It binds to the C-terminal, non-catalytic domain of lipase, thereby stabilizing an active conformation and considerably increasing the overall hydrophobic binding site. The gene product allows lipase to anchor noncovalently to the surface of lipid micelles, counteracting the destabilizing influence of intestinal bile salts. This cofactor is only expressed in pancreatic acinar cells, suggesting regulation of expression by tissue-specific elements. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1208 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_001832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2085
Approved symbol	CLPS
Name	colipase
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137392
Ensembl biotype	protein_coding
OMIM	120105
Entrez	1208

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000259938, ENST00000616014, ENST00000622413, ENST00000912425

RefSeq mRNA: 3 — MANE Select: NM_001832 NM_001252597, NM_001252598, NM_001832

CCDS: CCDS4811, CCDS75437, CCDS75438

Canonical transcript exons

ENST00000259938 — 3 exons

Exon	Start	End
ENSE00000929523	35795731	35795853
ENSE00000929524	35797205	35797323
ENSE00001031985	35794982	35795277

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 244.7918 / max 372553.2649, expressed in 28 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73324	244.7918	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.99	gold quality
pancreas	UBERON:0001264	99.19	gold quality
islet of Langerhans	UBERON:0000006	99.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.81	gold quality
epithelial cell of pancreas	CL:0000083	89.20	gold quality
type B pancreatic cell	CL:0000169	88.67	gold quality
right coronary artery	UBERON:0001625	84.54	gold quality
pancreatic ductal cell	CL:0002079	82.31	silver quality
ectocervix	UBERON:0012249	82.29	gold quality
right uterine tube	UBERON:0001302	80.97	gold quality
descending thoracic aorta	UBERON:0002345	80.64	gold quality
right lobe of liver	UBERON:0001114	80.55	gold quality
oocyte	CL:0000023	80.32	gold quality
endocervix	UBERON:0000458	79.92	gold quality
body of stomach	UBERON:0001161	79.68	gold quality
metanephros cortex	UBERON:0010533	79.10	gold quality
right adrenal gland	UBERON:0001233	78.69	gold quality
left uterine tube	UBERON:0001303	78.65	gold quality
fundus of stomach	UBERON:0001160	76.78	gold quality
right adrenal gland cortex	UBERON:0035827	74.95	gold quality
lower esophagus mucosa	UBERON:0035834	74.61	gold quality
left adrenal gland cortex	UBERON:0035825	74.34	gold quality
secondary oocyte	CL:0000655	73.91	gold quality
stomach	UBERON:0000945	73.31	gold quality
adrenal cortex	UBERON:0001235	73.03	gold quality
left adrenal gland	UBERON:0001234	72.68	gold quality
thoracic aorta	UBERON:0001515	71.90	gold quality
mucosa of stomach	UBERON:0001199	71.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.77	gold quality
right ovary	UBERON:0002118	71.70	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	52515.73
E-ENAD-27	yes	6.95
E-HCAD-31	no	3.26
E-GEOD-83139	no	3.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting CLPS, 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-10401-5P	99.99	65.79	948
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4486	96.96	60.61	931

Literature-anchored findings (GeneRIF, showing 6)

• evidence in two German Caucasian study populations that the variant of the rare colipase Arg109Cys polymorphism might contribute to increased susceptibility of type 2 diabetes (PMID:16189801)
• Our findings demonstrate that the Arg92Cys polymorphism decreases the function of Cys92 colipase. This change may contribute to the development of type 2 diabetes. (PMID:17715423)
• CLPS genetic variability associates with insulin secretory function in non-diabetic humans and may represent a novel candidate gene for development of type 2 diabetes (PMID:18726866)
• found no evidence for an association of pancreatic colipase(CLPS) single nucleotide polymorphisms rs2766597, rs41270082, rs3748050, and rs3748051 with obesity or percentage of dietary fat intake (PMID:20054203)
• humans with the Arg92Cys substitution will secrete less functional colipase (PMID:23204298)
• Low CLPS expression is associated with pancreatic cancer. (PMID:23918603)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clps	ENSMUSG00000024225
rattus_norvegicus	Clps	ENSRNOG00000000510

Paralogs (3): CLPSL2 (ENSG00000196748), CLPSL1 (ENSG00000204140), LRCOL1 (ENSG00000204583)

Protein

Protein identifiers

Colipase — P04118 (reviewed: P04118)

All UniProt accessions (3): A0A087WZW1, A0A087X0Q7, P04118

UniProt curated annotations — full annotation on UniProt →

Function. Colipase is a cofactor of pancreatic lipase. It allows the lipase to anchor itself to the lipid-water interface. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase. Enterostatin has a biological activity as a satiety signal.

Subunit / interactions. Forms a 1:1 stoichiometric complex with pancreatic lipase.

Subcellular location. Secreted.

Tissue specificity. Expressed by the pancreas.

Polymorphism. Variant Cys-109 is statistically significantly associated with an increased risk of type 2 diabetes.

Similarity. Belongs to the colipase family.

RefSeq proteins (3): NP_001239526, NP_001239527, NP_001823* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001981	Colipase	Family
IPR017913	Colipase_N	Domain
IPR017914	Colipase_C	Domain
IPR017915	Colipase_CS	Conserved_site
IPR047576	CLPS_chr	Family

Pfam: PF01114, PF02740

UniProt features (10 total): disulfide bond 5, sequence variant 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04118-F1	87.89	0.62

Functional residue map

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

Disulfide bonds (5): 34–45, 40–56, 44–78, 66–86, 80–104

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-192456	Digestion of dietary lipid
R-HSA-975634	Retinoid metabolism and transport

MSigDB gene sets: 78 (showing top): GOBP_DIGESTION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CAGCTG_AP4_Q5, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_ISOPRENOID_METABOLIC_PROCESS, AP4_01, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS, GOMF_ENZYME_ACTIVATOR_ACTIVITY, KIM_MYCN_AMPLIFICATION_TARGETS_UP, GOBP_RESPONSE_TO_BACTERIUM, GOMF_ENZYME_REGULATOR_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, MARTENS_TRETINOIN_RESPONSE_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A

GO Biological Process (7): retinoid metabolic process (GO:0001523), lipid metabolic process (GO:0006629), digestion (GO:0007586), response to bacterium (GO:0009617), lipid catabolic process (GO:0016042), response to food (GO:0032094), positive regulation of catalytic activity (GO:0043085)

GO Molecular Function (2): enzyme activator activity (GO:0008047), lipase binding (GO:0035473)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Digestion	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
diterpenoid metabolic process	1
primary metabolic process	1
multicellular organismal process	1
response to other organism	1
lipid metabolic process	1
catabolic process	1
response to nutrient levels	1
response to chemical	1
positive regulation of molecular function	1
regulation of catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
enzyme binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLPS	PNLIP	P16233	999
CLPS	PNLIPRP1	P54315	959
CLPS	LIPF	P07098	944
CLPS	TBX22	Q9Y458	940
CLPS	PROK1	P58294	769
CLPS	REG1A	P05451	743
CLPS	CEL	P19835	740
CLPS	PROK2	Q9HC23	733
CLPS	LPL	P06858	676
CLPS	LIPC	P11150	676
CLPS	CLPP	Q16740	658
CLPS	CTRB1	P17538	587
CLPS	CTRB2	Q6GPI1	582
CLPS	CLPX	O76031	573
CLPS	PER2	O15055	544

IntAct

0 interactions, top by confidence:

BioGRID (3): CLPS (PCA), S (Reconstituted Complex), S (Reconstituted Complex)

ESM2 similar proteins: A0A384E0Y8, A0JNQ7, A9JSD6, A9XFZ7, D2Y2C0, D2Y2E1, D2Y2E2, D2Y2E3, D2Y2E4, D2Y2E5, D3ZVN1, O75711, O96049, P02703, P02704, P02705, P04118, P08162, P0CJ14, P0DQT9, P0DQU0, P0DQU1, P0DRJ0, P11858, P17084, P19090, P42889, P42890, P80407, P83668, Q07663, Q27023, Q3UW21, Q5BQU9, Q5BQX9, Q5D231, Q5D232, Q5D233, Q5W280, Q6UWE3

Diamond homologs: A0JNQ7, A2RUU4, A9JSD6, P02703, P02704, P02705, P04118, P11148, P11149, P17084, P19090, P42889, P42890, Q91XL7, Q9CQC2, D3ZVN1, Q3UW21, Q6UWE3, Q8JFY0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

226 predictions. Top by Δscore:

Variant	Effect	Δscore
6:35795275:CGT:C	acceptor_gain	0.9900
6:35797199:TCTTA:T	donor_loss	0.9900
6:35797200:CTTA:C	donor_loss	0.9900
6:35797201:TTACC:T	donor_loss	0.9900
6:35797202:TA:T	donor_loss	0.9900
6:35797203:A:AT	donor_loss	0.9900
6:35797204:C:CT	donor_loss	0.9900
6:35795274:GCGT:G	acceptor_gain	0.9800
6:35795275:CGTC:C	acceptor_gain	0.9800
6:35795276:GT:G	acceptor_gain	0.9800
6:35795276:GTC:G	acceptor_loss	0.9800
6:35795277:TCTGC:T	acceptor_loss	0.9800
6:35795278:C:CC	acceptor_gain	0.9800
6:35795278:CTGCA:C	acceptor_loss	0.9800
6:35795279:T:A	acceptor_loss	0.9800
6:35797203:A:AC	donor_gain	0.9800
6:35797204:C:CC	donor_gain	0.9800
6:35797204:CCAGG:C	donor_gain	0.9800
6:35795281:C:CT	acceptor_gain	0.9500
6:35795726:CCCA:C	donor_loss	0.9500
6:35795727:CCA:C	donor_loss	0.9500
6:35795728:CA:C	donor_loss	0.9500
6:35795729:A:AG	donor_loss	0.9500
6:35795730:CCTT:C	donor_loss	0.9500
6:35795851:CTC:C	acceptor_gain	0.9500
6:35795853:CCTGC:C	acceptor_loss	0.9500
6:35795854:C:CA	acceptor_loss	0.9500
6:35795855:T:A	acceptor_loss	0.9500
6:35795273:AGCGT:A	acceptor_gain	0.9400
6:35795856:G:C	acceptor_loss	0.9400

AlphaMissense

730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:35795174:C:G	C104S	0.997
6:35795175:A:T	C104S	0.997
6:35795771:C:G	C56S	0.997
6:35795772:A:T	C56S	0.997
6:35795819:C:G	C40S	0.997
6:35795820:A:T	C40S	0.997
6:35795741:C:G	C66S	0.996
6:35795742:A:T	C66S	0.996
6:35795837:C:G	C34S	0.996
6:35795838:A:T	C34S	0.996
6:35795804:C:G	C45S	0.995
6:35795805:A:T	C45S	0.995
6:35795174:C:T	C104Y	0.994
6:35795228:C:G	C86S	0.994
6:35795229:A:T	C86S	0.994
6:35795770:G:C	C56W	0.994
6:35795818:A:C	C40W	0.994
6:35795836:G:C	C34W	0.994
6:35795837:C:T	C34Y	0.994
6:35795173:G:C	C104W	0.993
6:35795205:C:A	G94C	0.993
6:35795246:C:G	C80S	0.993
6:35795246:C:T	C80Y	0.993
6:35795247:A:T	C80S	0.993
6:35795772:A:G	C56R	0.993
6:35795819:C:T	C40Y	0.993
6:35795234:A:G	L84P	0.992
6:35795740:G:C	C66W	0.992
6:35795803:G:C	C45W	0.992
6:35795175:A:G	C104R	0.991

dbSNP variants (sampled 300 via entrez): RS1000473684 (6:35798989 T>C), RS1000840014 (6:35795736 C>A), RS1000953974 (6:35795606 C>A,T), RS1002846308 (6:35797786 T>C), RS1003238907 (6:35798913 T>A), RS1003312104 (6:35798677 G>A,T), RS1004904668 (6:35796240 C>A), RS1005247750 (6:35798450 C>T), RS1006752242 (6:35798106 A>G), RS1007322281 (6:35794512 T>C), RS1007631126 (6:35795344 C>T), RS1009309823 (6:35798925 G>A), RS1009324479 (6:35799257 G>A), RS1009508584 (6:35797039 C>G,T), RS1011669647 (6:35798096 C>A,T)

Disease associations

OMIM: gene MIM:120105 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1920	Blood protein levels	6.000000e-80

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
sodium arsenite	affects expression	1
Olive Oil	affects cotreatment, decreases reaction, increases hydrolysis	1
Orlistat	increases hydrolysis, affects cotreatment, decreases reaction	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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