CLEC5A

Summary

CLEC5A (C-type lectin domain containing 5A, HGNC:2054) is a protein-coding gene on chromosome 7q34, encoding C-type lectin domain family 5 member A (Q9NY25). Functions as a positive regulator of osteoclastogenesis.

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined.

Source: NCBI Gene 23601 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 30 total — 1 pathogenic
• MANE Select transcript: NM_013252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2054
Approved symbol	CLEC5A
Name	C-type lectin domain containing 5A
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	MDL-1
Ensembl gene	ENSG00000258227
Ensembl biotype	protein_coding
OMIM	604987
Entrez	23601

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000418498, ENST00000438351, ENST00000439991, ENST00000470595, ENST00000481301, ENST00000546910, ENST00000551012, ENST00000904721, ENST00000904722, ENST00000904723, ENST00000960422, ENST00000960423

RefSeq mRNA: 2 — MANE Select: NM_013252 NM_001301167, NM_013252

CCDS: CCDS5870, CCDS75670

Canonical transcript exons

ENST00000546910 — 7 exons

Exon	Start	End
ENSE00002326291	141946807	141946974
ENSE00002336803	141946214	141946312
ENSE00002371414	141943896	141943964
ENSE00002385256	141927357	141930218
ENSE00002415310	141935814	141935950
ENSE00003570478	141945341	141945400
ENSE00003620767	141931720	141931826

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 89.17.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8998 / max 338.0123, expressed in 261 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86598	4.3590	254
86599	0.3334	101
86597	0.2075	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	89.17	gold quality
bone marrow cell	CL:0002092	87.21	gold quality
trabecular bone tissue	UBERON:0002483	85.25	gold quality
monocyte	CL:0000576	84.99	gold quality
mononuclear cell	CL:0000842	84.30	gold quality
leukocyte	CL:0000738	83.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.30	gold quality
right coronary artery	UBERON:0001625	78.34	gold quality
granulocyte	CL:0000094	74.43	gold quality
upper lobe of left lung	UBERON:0008952	73.39	gold quality
upper lobe of lung	UBERON:0008948	72.70	gold quality
tibial nerve	UBERON:0001323	72.12	gold quality
descending thoracic aorta	UBERON:0002345	71.92	gold quality
blood	UBERON:0000178	70.68	gold quality
left adrenal gland	UBERON:0001234	69.99	gold quality
amniotic fluid	UBERON:0000173	69.60	gold quality
thoracic aorta	UBERON:0001515	69.40	gold quality
left coronary artery	UBERON:0001626	69.29	gold quality
ascending aorta	UBERON:0001496	68.96	gold quality
aorta	UBERON:0000947	68.92	gold quality
tibial artery	UBERON:0007610	68.92	gold quality
popliteal artery	UBERON:0002250	68.86	gold quality
vermiform appendix	UBERON:0001154	68.62	gold quality
left adrenal gland cortex	UBERON:0035825	68.53	gold quality
coronary artery	UBERON:0001621	68.43	gold quality
right adrenal gland cortex	UBERON:0035827	67.80	gold quality
gall bladder	UBERON:0002110	67.79	gold quality
right lung	UBERON:0002167	67.59	gold quality
islet of Langerhans	UBERON:0000006	66.75	gold quality
adrenal cortex	UBERON:0001235	66.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.79
E-MTAB-9801	yes	7.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

89 targeting CLEC5A, 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-371B-5P	99.99	75.34	4759
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1252-3P	99.55	67.71	2862

Literature-anchored findings (GeneRIF, showing 24)

• blockade of CLEC5A-mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with Dengue virus (either alone or complexed with an enhancing antibody) (PMID:18496526)
• The crystal volume per unit weight (VM) was calculated to be 2.34 A3 Da-1, with nine molecules per asymmetric unit and a solvent content of 47.38%. CLEC5A plays an important role in the pathophysiology of dengue-virus-induced disease. (PMID:20057064)
• CLEC5A expression in monocyte/macrophage and granulocytes is regulated by PU.1. (PMID:21094529)
• CLEC5A is homodimeric at the cell surface and binds to dengue virus serotypes 1-4. (PMID:21566123)
• No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and Kawasaki disease patients. (PMID:22536019)
• Blockade of CLEC5A inhibits NLRP3 inflammasome activation and pyrotopsis in dengue-virus-infected inflammatory macrophages. Thus, DV can activate NLRP3 inflammasome via CLEC5A. (PMID:23152543)
• Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in rheumatoid arthritis patients. (PMID:24465901)
• CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis (PMID:27033255)
• The results suggest that CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza pathogenicity in vivo and may be considered a therapeutic target in combination with effective antivirals. (PMID:27795434)
• Mannose Receptor and CLEC5A on Macrophage first attracts the Dengue Virus with high avidity, and the virus concurrently interacts with CLEC5A in close proximity to form a multivalent hetero-complex and facilitate CLEC5A-mediated signal transduction. Dengue Virus Infection Is through a Cooperative Interaction between a Mannose Receptor and CLEC5A on Macrophage as a Multivalent Hetero-Complex. (PMID:27832191)
• this study shows association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity (PMID:28764923)
• MDL-1 is mainly expressed in atherosclerotic lesional macrophages and increased macrophage MDL-1 expression is associated with early plaque progression and promotes macrophage survival. (PMID:29126450)
• CLEC5A was highly upregulated in glioblastoma compared to normal brain tissues, which had an opposite relation with the overall patient survival. Downregulation of CLEC5A could inhibit cell proliferation, migration and invasion via promoting apoptosis and G1 arrest. (PMID:30834619)
• CEBPB can inhibit the proliferation of osteosarcoma cells via regulating the expression of CLEC5A. (PMID:31364785)
• CLEC5A expressed on myeloid cells as a M2 biomarker relates to immunosuppression and decreased survival in patients with glioma. (PMID:31591460)
• CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections. (PMID:31867016)
• CLEC5A promotes the proliferation of gastric cancer cells by activating the PI3K/AKT/mTOR pathway. (PMID:32033754)
• REVIEW: CLEC5A, a Promiscuous Pattern Recognition Receptor to Microbes and Beyond (PMID:32152943)
• Genetic association analysis of CLEC5A and CLEC7A gene single-nucleotide polymorphisms and Crohn’s disease. (PMID:32476786)
• Activation of the Innate Immune Checkpoint CLEC5A on Myeloid Cells in the Absence of Danger Signals Modulates Macrophages’ Function but Does Not Trigger the Adaptive T Cell Immune Response. (PMID:35252461)
• CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation. (PMID:35820906)
• CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy. (PMID:36571274)
• [Overexpression of CLEC5A inhibits cell proliferation and metastasis and reverses epithelial-mesenchymal transition in hepatocellular carcinoma]. (PMID:36856214)
• The influence of CLEC5A on early macrophage-mediated inflammation in COPD progression. (PMID:39097839)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-193e13.5	ENSDARG00000052656
danio_rerio		ENSDARG00000074732
danio_rerio	si:dkey-26c10.5	ENSDARG00000088023
danio_rerio	si:ch211-170d8.8	ENSDARG00000090945
mus_musculus	Clec5a	ENSMUSG00000029915
rattus_norvegicus	Clec5a	ENSRNOG00000026306
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), KLRG1 (ENSG00000139187), KLRF1 (ENSG00000150045), CLEC1A (ENSG00000150048), CLEC1B (ENSG00000165682), CLEC7A (ENSG00000172243), CLEC12A (ENSG00000172322), OLR1 (ENSG00000173391), KLRC4 (ENSG00000183542), CLEC2A (ENSG00000188393), KLRG2 (ENSG00000188883), CLEC9A (ENSG00000197992), KLRC2 (ENSG00000205809), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797)

Protein

Protein identifiers

C-type lectin domain family 5 member A — Q9NY25 (reviewed: Q9NY25)

Alternative names: C-type lectin superfamily member 5, Myeloid DAP12-associating lectin 1

All UniProt accessions (6): Q9NY25, A4D1U7, C9JCE4, C9JPR7, F8WCL0, Q14DL9

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a positive regulator of osteoclastogenesis. Cell surface receptor that signals via TYROBP. Regulates inflammatory responses. (Microbial infection) Critical macrophage receptor for dengue virus serotypes 1-4. The binding of dengue virus to CLEC5A triggers signaling through the phosphorylation of TYROBP. This interaction does not result in viral entry, but stimulates pro-inflammatory cytokine release.

Subunit / interactions. Monomer. Homodimer. The majority of CLEC5A is expressed as a monomeric form on macrophages. Interacts with TYROBP/DAP12. The interaction with TYROBP is required for CLEC5A cell surface expression. Interacts with HCST/DAP10. Forms a CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP. (Microbial infection) Interacts with dengue virus envelope protein E.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in bone marrow with lower levels in synovium, lung and bronchus. Expressed in peripheral blood monocytes and in the monocyte/macrophage cell lines U-937 and Mono-Mac-6, but not in cell lines of other origins. Expression is down-regulated when monocytes differentiate into dendritic cells.

Post-translational modifications. N-glycosylated. Contains sialic acid residues.

Miscellaneous. Acts as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation when its activation leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joints.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NY25-1	1	yes
Q9NY25-2	2

RefSeq proteins (2): NP_001288096, NP_037384* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR033992	NKR-like_CTLD	Domain
IPR052869	CLEC5A	Family

Pfam: PF00059

UniProt features (27 total): strand 7, glycosylation site 4, disulfide bond 3, turn 3, topological domain 2, helix 2, chain 1, splice variant 1, sequence variant 1, mutagenesis site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YHF	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY25-F1	85.83	0.71

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 (3): 99–183, 161–175, 71–82

Glycosylation sites (4): 32, 93, 144, 151

Mutagenesis-validated functional residues (1):

Position	Phenotype
16	abolishes interaction with tyrobp.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2172127	DAP12 interactions
R-HSA-6798695	Neutrophil degranulation
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses

MSigDB gene sets: 183 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOCC_CELL_SURFACE, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, RIZKI_TUMOR_INVASIVENESS_3D_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CYTOKINE_PRODUCTION, WTGAAAT_UNKNOWN, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, GOBP_VIRAL_LIFE_CYCLE, GOBP_OSSIFICATION

GO Biological Process (10): positive regulation of cytokine production (GO:0001819), osteoblast development (GO:0002076), cellular defense response (GO:0006968), signal transduction (GO:0007165), myeloid cell differentiation (GO:0030099), negative regulation of myeloid cell apoptotic process (GO:0033033), negative regulation of apoptotic process (GO:0043066), innate immune response (GO:0045087), immune system process (GO:0002376), symbiont entry into host cell (GO:0046718)

GO Molecular Function (2): virus receptor activity (GO:0001618), carbohydrate binding (GO:0030246)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), specific granule membrane (GO:0035579), tertiary granule membrane (GO:0070821), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	2
Dengue Virus-Host Interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
secretory granule membrane	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
osteoblast differentiation	1
cell development	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
hemopoiesis	1
cell differentiation	1
myeloid cell apoptotic process	1
regulation of myeloid cell apoptotic process	1
negative regulation of apoptotic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
immune response	1
defense response to symbiont	1
biological_process	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
specific granule	1
tertiary granule	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC5A	TYROBP	O43914	990
CLEC5A	HCST	Q9UBK5	875
CLEC5A	SYK	P43405	844
CLEC5A	FCER1G	P30273	767
CLEC5A	MGAM	O43451	711
CLEC5A	TREM1	Q9NP99	668
CLEC5A	CLEC1B	Q9P126	638
CLEC5A	LY75	O60449	542
CLEC5A	CLEC9A	Q6UXN8	528
CLEC5A	FCGR3B	O75015	515
CLEC5A	FCGR3A	P08637	502
CLEC5A	STAT1	P42224	490
CLEC5A	CLEC4A	Q9UMR7	474
CLEC5A	TSPAN6	O43657	465
CLEC5A	TREM2	Q9NZC2	461

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CLEC5A	TSPAN6	psi-mi:“MI:0914”(association)	0.530

BioGRID (43): DAD1 (Affinity Capture-MS), ECSIT (Affinity Capture-MS), PTRH2 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CHCHD6 (Affinity Capture-MS), REEP5 (Affinity Capture-MS), PIGU (Affinity Capture-MS), DPP9 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), TMBIM6 (Affinity Capture-MS), YIF1A (Affinity Capture-MS), MTX3 (Affinity Capture-MS), CD276 (Affinity Capture-MS), TSPAN6 (Affinity Capture-MS), EMC8 (Affinity Capture-MS)

ESM2 similar proteins: A4KWA5, A4KWA6, A4KWA8, A7TZG3, B2KG20, D4AD02, O54709, O70215, P01590, P26717, P26718, P27811, P37217, P61252, Q07108, Q07444, Q0H8B9, Q149M0, Q3TB92, Q504P2, Q5DT36, Q5DT37, Q5DT39, Q5M9I1, Q60654, Q62875, Q6PNM1, Q7TSA3, Q80XD9, Q8C1T8, Q8MJH1, Q8TDQ0, Q8VBX4, Q8VI21, Q8VIM0, Q91V08, Q925N7, Q95MI4, Q9D676, Q9GLF3

Diamond homologs: A4KWA1, A4KWA6, P20693, P20937, P21063, P24765, P27471, P27811, P27812, P27814, P79391, Q0ZUP0, Q0ZUP1, Q12918, Q49BZ4, Q5NKN2, Q5NKN4, Q60651, Q60654, Q61830, Q63378, Q67EQ1, Q8HY06, Q8HY10, Q8HY11, Q8HY12, Q8HYC0, Q8VD98, Q8WTT0, Q90WJ8, Q91ZW8, Q925N7, Q95LG1, Q99JB4, Q9GLF3, Q9GME8, Q9H2X3, Q9JKF4, Q9NY25, Q9QZ15

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
973567	NC_000007.13:g.141443350_142460881dup	Pathogenic

SpliceAI

678 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141931718:A:AC	donor_gain	1.0000
7:141931719:C:CC	donor_gain	1.0000
7:141931824:CTT:C	acceptor_gain	1.0000
7:141946803:TCAC:T	donor_loss	1.0000
7:141946804:CACCT:C	donor_loss	1.0000
7:141946806:CCT:C	donor_gain	1.0000
7:141930217:CA:C	acceptor_gain	0.9900
7:141930219:C:CC	acceptor_gain	0.9900
7:141931719:CTTG:C	donor_gain	0.9900
7:141931822:AACTT:A	acceptor_gain	0.9900
7:141931824:CTTCT:C	acceptor_gain	0.9900
7:141931825:TT:T	acceptor_gain	0.9900
7:141931827:C:CC	acceptor_gain	0.9900
7:141944155:TGAC:T	donor_gain	0.9900
7:141946805:A:AC	donor_gain	0.9900
7:141946806:C:CC	donor_gain	0.9900
7:141931714:ACGT:A	donor_loss	0.9800
7:141931716:GTA:G	donor_loss	0.9800
7:141931717:T:TC	donor_loss	0.9800
7:141931718:AC:A	donor_loss	0.9800
7:141931719:C:T	donor_loss	0.9800
7:141931823:ACTTC:A	acceptor_gain	0.9800
7:141931827:C:A	acceptor_loss	0.9800
7:141931828:T:A	acceptor_loss	0.9800
7:141931833:A:AC	acceptor_gain	0.9800
7:141935963:A:T	acceptor_gain	0.9800
7:141943965:C:CC	acceptor_gain	0.9800
7:141944154:TTGA:T	donor_gain	0.9800
7:141946212:A:AC	donor_gain	0.9800
7:141946213:C:CC	donor_gain	0.9800

AlphaMissense

1261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:141931752:C:A	W140C	0.988
7:141931752:C:G	W140C	0.988
7:141931746:C:A	W142C	0.987
7:141931746:C:G	W142C	0.987
7:141935934:C:A	W75C	0.981
7:141935934:C:G	W75C	0.981
7:141935883:C:A	W92C	0.980
7:141935883:C:G	W92C	0.980
7:141931748:A:G	W142R	0.970
7:141931748:A:T	W142R	0.970
7:141931754:A:G	W140R	0.970
7:141931754:A:T	W140R	0.970
7:141935863:C:G	C99S	0.969
7:141935864:A:T	C99S	0.969
7:141930189:C:G	C161S	0.965
7:141930190:A:T	C161S	0.965
7:141931780:A:G	L131S	0.964
7:141935914:C:G	C82S	0.964
7:141935915:A:T	C82S	0.964
7:141930147:C:G	C175S	0.962
7:141930148:A:T	C175S	0.962
7:141935863:C:T	C99Y	0.962
7:141930123:C:G	C183S	0.961
7:141930124:A:T	C183S	0.961
7:141935874:G:C	S95R	0.958
7:141935874:G:T	S95R	0.958
7:141935876:T:G	S95R	0.958
7:141935849:A:G	S104P	0.955
7:141930147:C:T	C175Y	0.949
7:141931788:A:C	F128L	0.948

dbSNP variants (sampled 300 via entrez): RS1000256614 (7:141943186 A>G), RS1000399374 (7:141926974 G>A,C,T), RS1001050482 (7:141937449 G>A,C), RS1001081301 (7:141937212 G>A,C), RS1001139024 (7:141937856 A>G), RS1001264042 (7:141937512 C>G,T), RS1001769190 (7:141943553 T>C), RS1002396307 (7:141932179 A>C), RS1002422258 (7:141931883 C>G), RS1003397843 (7:141933646 A>C,G,T), RS1003428860 (7:141933441 C>A,T), RS1003526297 (7:141939391 G>A), RS1003657444 (7:141944948 C>G,T), RS1003688565 (7:141944606 G>C), RS1003880636 (7:141945512 A>G)

Disease associations

OMIM: gene MIM:604987 | disease phenotypes: MIM:167800

GenCC curated gene-disease

Mondo (1): hereditary chronic pancreatitis (MONDO:0008185)

Orphanet (1): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001961_2	Anorexia nervosa	2.000000e-07
GCST009819_1	Compulsion score in obsessive compulsive disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007802	obsessive-compulsive symptom measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537262	Hereditary pancreatitis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzene	increases expression, affects expression	3
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	decreases methylation	1
sodium arsenite	increases expression	1
nickel chloride	affects expression, increases expression	1
perfluorooctanoic acid	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
phellopterin	decreases expression	1
bisphenol S	increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cholesterol	increases expression, increases reaction	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Dinitrochlorobenzene	affects expression, increases expression	1
Testosterone	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00830557	Not specified	RECRUITING	Collecting Medical Information and Tissue Samples From Patients With Pancreatic Cancer or Other Pancreatic Disorders
NCT02078245	Not specified	UNKNOWN	Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer.
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT02309632	Not specified	WITHDRAWN	Pancreatic Cancer Screening of High-Risk Individuals in Arkansas
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT04743479	Not specified	RECRUITING	Artificial Intelligence-based Early Screening of Pancreatic Cancer and High Risk Tracing (ESPRIT-AI)
NCT07413029	Not specified	RECRUITING	French National Cohort of Patients With PRSS1 Mutations