LEAP2

Summary

LEAP2 (liver enriched antimicrobial peptide 2, HGNC:29571) is a protein-coding gene on chromosome 5q31.1, encoding Liver-expressed antimicrobial peptide 2 (Q969E1). Has an antimicrobial activity.

This gene encodes a cysteine-rich cationic antimicrobial peptide that is expressed predominantly in the liver. The mature peptide has activity against gram-positive bacteria and yeasts.

Source: NCBI Gene 116842 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_052971

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29571
Approved symbol	LEAP2
Name	liver enriched antimicrobial peptide 2
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	LEAP-2
Ensembl gene	ENSG00000164406
Ensembl biotype	protein_coding
OMIM	611373
Entrez	116842

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000296877, ENST00000483190, ENST00000485457, ENST00000872294

RefSeq mRNA: 1 — MANE Select: NM_052971 NM_052971

CCDS: CCDS4163

Canonical transcript exons

ENST00000296877 — 3 exons

Exon	Start	End
ENSE00001084109	132873668	132873751
ENSE00001913540	132874410	132875046
ENSE00003514099	132873950	132874089

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 98.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7001 / max 234.2375, expressed in 50 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58508	0.7001	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.83	gold quality
liver	UBERON:0002107	98.79	gold quality
jejunal mucosa	UBERON:0000399	98.22	gold quality
duodenum	UBERON:0002114	87.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.93	gold quality
mucosa of transverse colon	UBERON:0004991	83.93	gold quality
jejunum	UBERON:0002115	83.49	gold quality
small intestine	UBERON:0002108	80.58	gold quality
urinary bladder	UBERON:0001255	80.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.08	gold quality
cerebellar hemisphere	UBERON:0002245	79.85	gold quality
cerebellar cortex	UBERON:0002129	79.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.30	gold quality
cerebellum	UBERON:0002037	79.02	gold quality
lower esophagus mucosa	UBERON:0035834	78.22	gold quality
adult mammalian kidney	UBERON:0000082	77.01	gold quality
kidney	UBERON:0002113	76.88	gold quality
tibia	UBERON:0000979	76.48	gold quality
body of stomach	UBERON:0001161	75.35	gold quality
fundus of stomach	UBERON:0001160	75.07	gold quality
oocyte	CL:0000023	74.48	silver quality
spleen	UBERON:0002106	74.33	gold quality
gall bladder	UBERON:0002110	74.20	gold quality
intestine	UBERON:0000160	74.11	gold quality
transverse colon	UBERON:0001157	73.67	gold quality
right uterine tube	UBERON:0001302	73.60	gold quality
muscle of leg	UBERON:0001383	73.60	gold quality
metanephros cortex	UBERON:0010533	73.60	gold quality
cerebellar vermis	UBERON:0004720	73.59	silver quality
hindlimb stylopod muscle	UBERON:0004252	73.51	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	62.70
E-MTAB-10553	yes	30.87
E-CURD-11	no	14.68
E-HCAD-5	no	2.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting LEAP2, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-6849-3P	97.25	64.57	1371

Literature-anchored findings (GeneRIF, showing 17)

• These results show that the secondary structure of human LEAP-2 has a profound impact on its antibacterial activity. (PMID:19852990)
• Data suggest that LEAP-2 is not involved in the physiological response of GI epithelia to iron, nor is it mitogenic for epithelial cells or chemotactic for THP-1 monocytes. (PMID:20038463)
• LEAP-2 displays antimicrobial activity against bacteria and yeasts. (PMID:20845358)
• LEAP-2 has a novel fold for a cationic antimicrobial peptide and has antibacterial activity. LEAP-2 exhibits antimicrobial activity under low-salt conditions, and there is likely to be another physiological role for the peptide. (PMID:20845358)
• We identified the amphibian leap2 gene which is highly related to its mammalian orthologues at both structural and sequence levels. The gene is expressed in the embryo mostly in the endoderm-derived tissues. Accordingly it is induced in pluripotent animal cap cells by FGF, activin or a combination of vegT/beta-catenin. (PMID:27335344)
• plasma LEAP2/acyl-ghrelin molar ratio may be a key determinant modulating acyl-ghrelin activity in response to body mass, feeding status, and blood glucose. (PMID:31424424)
• Decreased levels of liver-expressed antimicrobial peptide-2 and ghrelin are related to insulin resistance in women with polycystic ovary syndrome. (PMID:31526069)
• findings suggest that ghrelin tone is increased in childhood obesity, due to a decrease on plasma levels of des-acyl ghrelin and LEAP2, and that des-acyl ghrelin is associated to insulin resistance, particularly in children with overweight/obesity (PMID:31770106)
• Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis. (PMID:32268520)
• Identifying key residues and key interactions for the binding of LEAP2 to receptor GHSR1a. (PMID:32803260)
• Circulating LEAP-2 is associated with puberty in girls. (PMID:33139887)
• Human liver-expressed antimicrobial peptide 2 elevation in the cerebrospinal fluid in bacterial meningitis. (PMID:33811478)
• LEAP2 has antagonized the ghrelin receptor GHSR1a since its emergence in ancient fish. (PMID:33966114)
• LEAP-2/ghrelin interplay in adult growth hormone deficiency: Cause or consequence? A pilot study. (PMID:33991145)
• Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy. (PMID:36076912)
• LEAP2 is associated with cardiometabolic markers but is unchanged by antidiabetic treatment in people with prediabetes. (PMID:37436962)
• The LEAP2 Response to Cancer-Related Anorexia-Cachexia Syndrome in Male Mice and Patients. (PMID:39331742)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-22f5.9	ENSDARG00000092044
mus_musculus	Leap2	ENSMUSG00000036216
rattus_norvegicus	Leap2	ENSRNOG00000007218

Protein

Protein identifiers

Liver-expressed antimicrobial peptide 2 — Q969E1 (reviewed: Q969E1)

All UniProt accessions (1): Q969E1

UniProt curated annotations — full annotation on UniProt →

Function. Has an antimicrobial activity.

Subcellular location. Secreted.

Similarity. Belongs to the LEAP2 family.

RefSeq proteins (1): NP_443203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009955	LEAP-2	Family

Pfam: PF07359

UniProt features (7 total): disulfide bond 2, signal peptide 1, propeptide 1, chain 1, strand 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2L1Q	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969E1-F1	76.92	0.15

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 (2): 54–65, 60–70

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 80 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MODULE_503, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GATA3_01, MODULE_195, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, TGCTGAY_UNKNOWN, HNF4_01, GOBP_HUMORAL_IMMUNE_RESPONSE, TATA_C, MODULE_147, AACTTT_UNKNOWN, HNF1_01, GOBP_RESPONSE_TO_FUNGUS

GO Biological Process (1): defense response to bacterium (GO:0042742)

GO Molecular Function (0):

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	1
response to bacterium	1
cellular anatomical structure	1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LEAP2	HAMP	P81172	917
LEAP2	GHSR	Q92847	784
LEAP2	GHRL	Q9UBU3	581
LEAP2	MOSPD2	Q8NHP6	574
LEAP2	MBOAT4	Q96T53	524
LEAP2	DEFB133	Q30KQ1	479
LEAP2	WFDC12	Q8WWY7	387
LEAP2	MRAP2	Q96G30	354
LEAP2	CAMP	P49913	352
LEAP2	APOA2	P02652	352
LEAP2	DEFB1	P60022	348
LEAP2	HAPSTR1	Q14CZ0	347
LEAP2	DEFB128	Q7Z7B8	346
LEAP2	DEFB127	Q9H1M4	346
LEAP2	RNASE7	P80927	344

IntAct

4 interactions, top by confidence:

A	B	Type	Score
LEAP2	PACS1	psi-mi:“MI:0914”(association)	0.350
LEAP2	GNB2	psi-mi:“MI:0914”(association)	0.350
LEAP2	RMND1	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): LEAP2 (Negative Genetic), PACS1 (Affinity Capture-MS), PACS2 (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), WDR37 (Affinity Capture-MS), PRSS8 (Affinity Capture-MS), NISCH (Affinity Capture-MS), UBR3 (Affinity Capture-MS), SMPDL3B (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GHSR (Reconstituted Complex)

ESM2 similar proteins: A1YL66, A1YL67, A1YL68, A1YL69, A1YL70, A1YL72, A1YL74, A1YL77, A1YL78, A1YL79, A1YL80, A1YL81, A1YL82, A8CEM0, A8CEM1, A8CEM4, A8CEM5, A8CEM7, A8CEM8, A8CEM9, A8CEN1, A8CEN3, P07467, P42127, P56473, P79407, Q03288, Q1XGU5, Q1XGU6, Q1XGU7, Q1XGU8, Q1XGU9, Q1XGV0, Q1XGV1, Q1XGV2, Q1XGV3, Q1XGV4, Q1XGV5, Q1XGV6, Q1XGV7

Diamond homologs: Q91V13, Q91X13, Q95JB4, Q95JC3, Q95M25, Q969E1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

278 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132874081:GC:G	donor_gain	0.9900
5:132874408:A:AG	acceptor_gain	0.9900
5:132874409:G:GG	acceptor_gain	0.9900
5:132874409:GA:G	acceptor_gain	0.9800
5:132873949:GATA:G	acceptor_gain	0.9700
5:132873607:A:AG	acceptor_gain	0.9600
5:132873608:G:GG	acceptor_gain	0.9600
5:132874404:CCCTA:C	acceptor_loss	0.9600
5:132874405:CCTAG:C	acceptor_loss	0.9600
5:132874407:TAGA:T	acceptor_loss	0.9600
5:132874408:A:G	acceptor_loss	0.9600
5:132874409:G:T	acceptor_loss	0.9600
5:132874409:GAAAA:G	acceptor_gain	0.9600
5:132873947:CAG:C	acceptor_loss	0.9400
5:132873948:A:AC	acceptor_loss	0.9400
5:132873948:A:AG	acceptor_gain	0.9400
5:132873949:G:GG	acceptor_gain	0.9400
5:132873949:GAT:G	acceptor_gain	0.9300
5:132874409:GAA:G	acceptor_gain	0.9300
5:132873580:A:G	acceptor_gain	0.9200
5:132874036:GCC:G	donor_gain	0.9100
5:132874085:TGCAG:T	donor_loss	0.9100
5:132874087:CAG:C	donor_loss	0.9100
5:132874088:AGGTA:A	donor_loss	0.9100
5:132874089:GGT:G	donor_loss	0.9100
5:132874090:G:T	donor_loss	0.9100
5:132874091:T:A	donor_loss	0.9100
5:132874409:GAAA:G	acceptor_gain	0.9100
5:132874058:G:T	donor_gain	0.8800
5:132874065:C:G	donor_gain	0.8600

AlphaMissense

493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132874070:T:A	C60S	0.990
5:132874071:G:C	C60S	0.990
5:132874018:G:C	W42C	0.989
5:132874018:G:T	W42C	0.989
5:132874420:T:A	C70S	0.986
5:132874421:G:C	C70S	0.986
5:132874052:T:A	C54S	0.984
5:132874053:G:C	C54S	0.984
5:132874070:T:C	C60R	0.982
5:132874085:T:A	C65S	0.981
5:132874086:G:C	C65S	0.981
5:132874072:T:G	C60W	0.978
5:132874422:T:G	C70W	0.978
5:132874021:A:C	R43S	0.977
5:132874021:A:T	R43S	0.977
5:132874053:G:A	C54Y	0.976
5:132874420:T:C	C70R	0.976
5:132874016:T:A	W42R	0.975
5:132874016:T:C	W42R	0.975
5:132874036:G:C	R48S	0.975
5:132874036:G:T	R48S	0.975
5:132874054:C:G	C54W	0.974
5:132874052:T:C	C54R	0.972
5:132874020:G:C	R43T	0.966
5:132874071:G:T	C60F	0.966
5:132874086:G:A	C65Y	0.963
5:132874071:G:A	C60Y	0.962
5:132874014:T:G	F41C	0.961
5:132874035:G:C	R48T	0.960
5:132874085:T:C	C65R	0.960

dbSNP variants (sampled 300 via entrez): RS1001789757 (5:132873308 T>C), RS1001911510 (5:132871730 T>C), RS1002279504 (5:132872906 A>G), RS1003464106 (5:132874472 A>G), RS1003927671 (5:132874451 C>T), RS1006024860 (5:132872884 TCAA>T), RS1006070702 (5:132872667 A>G), RS1006724642 (5:132873841 T>C), RS1006748275 (5:132875327 C>G,T), RS1007107619 (5:132874040 A>G), RS1007751254 (5:132873888 C>G,T), RS1008513396 (5:132874979 C>A), RS1010657614 (5:132873512 G>A), RS1010668134 (5:132872254 T>A), RS1010881788 (5:132874824 A>C)

Disease associations

OMIM: gene MIM:611373 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_986	Blood protein levels	4.000000e-19
GCST008916_34	Asthma	2.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	6
Aflatoxin B1	affects expression, decreases expression, decreases methylation	5
Cyclosporine	decreases expression	4
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	3
bisphenol A	affects expression, affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
methyleugenol	decreases expression	1
titanium dioxide	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Rosiglitazone	decreases expression	1
Bosentan	affects expression	1
Leflunomide	increases expression	1
Azathioprine	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Clozapine	increases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0VS	Ubigene Huh-7 LEAP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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