REG3G

Summary

REG3G (regenerating family member 3 gamma, HGNC:29595) is a protein-coding gene on chromosome 2p12, encoding Regenerating islet-derived protein 3-gamma (Q6UW15). Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan.

This gene encodes a member of the regenerating islet-derived genes (REG)3 protein family. These proteins are secreted, C-type lectins with a carbohydrate recognition domain and N-terminal signal peptide. The protein encoded by this gene is an antimicrobial lectin with activity against Gram-positive bacteria. Alternative splicing results in multiple transcript variants encoding multiple isoforms.

Source: NCBI Gene 130120 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001008387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29595
Approved symbol	REG3G
Name	regenerating family member 3 gamma
Location	2p12
Locus type	gene with protein product
Status	Approved
Aliases	UNQ429, LPPM429, PAP1B
Ensembl gene	ENSG00000143954
Ensembl biotype	protein_coding
OMIM	609933
Entrez	130120

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000272324, ENST00000393897, ENST00000409471, ENST00000490944, ENST00000498312, ENST00000870567, ENST00000944248

RefSeq mRNA: 3 — MANE Select: NM_001008387 NM_001008387, NM_001270040, NM_198448

CCDS: CCDS1962, CCDS58714

Canonical transcript exons

ENST00000272324 — 6 exons

Exon	Start	End
ENSE00001827400	79025702	79025773
ENSE00001929546	79028209	79028501
ENSE00002479283	79027034	79027171
ENSE00002521085	79027807	79027933
ENSE00002524356	79026713	79026831
ENSE00003615632	79025983	79026169

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 99.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3607 / max 210.2737, expressed in 9 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21125	0.1477	6
21127	0.0900	8
21126	0.0667	8
21124	0.0564	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.35	gold quality
pancreas	UBERON:0001264	96.02	gold quality
islet of Langerhans	UBERON:0000006	94.81	gold quality
right testis	UBERON:0004534	91.53	gold quality
left testis	UBERON:0004533	90.51	gold quality
right adrenal gland	UBERON:0001233	89.54	gold quality
testis	UBERON:0000473	88.63	gold quality
right adrenal gland cortex	UBERON:0035827	87.80	gold quality
left adrenal gland	UBERON:0001234	87.74	gold quality
left adrenal gland cortex	UBERON:0035825	85.88	gold quality
adrenal cortex	UBERON:0001235	84.79	gold quality
pancreatic ductal cell	CL:0002079	83.52	gold quality
ileal mucosa	UBERON:0000331	81.82	gold quality
adrenal gland	UBERON:0002369	79.81	gold quality
cauda epididymis	UBERON:0004360	77.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.80	gold quality
corpus epididymis	UBERON:0004359	76.64	gold quality
epithelial cell of pancreas	CL:0000083	74.42	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.91	gold quality
small intestine	UBERON:0002108	73.90	gold quality
oocyte	CL:0000023	72.53	gold quality
upper arm skin	UBERON:0004263	69.08	gold quality
duodenum	UBERON:0002114	68.40	gold quality
pons	UBERON:0000988	67.65	gold quality
nasal cavity epithelium	UBERON:0005384	66.70	gold quality
body of tongue	UBERON:0011876	66.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.42	gold quality
parotid gland	UBERON:0001831	65.21	gold quality
tibialis anterior	UBERON:0001385	65.10	silver quality
thymus	UBERON:0002370	65.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	5612.55
E-ANND-3	yes	19.34
E-MTAB-5061	yes	19.00
E-ENAD-27	yes	6.99
E-HCAD-31	yes	4.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, FOXA2

miRNA regulators (miRDB)

49 targeting REG3G, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767

Literature-anchored findings (GeneRIF, showing 7)

• REG III was identified and expressed predominantly in pancreas and testis, but not in small intestine (PMID:15556304)
• PAP IB represents a good example of duplication and divergence, probably with the acquisition of new functions, thus participating in the evolution of the protein repertoire. (PMID:15777617)
• This gene encodes a secreted peptide that displays antimicrobial activity against Gram-positive bacteria. (PMID:16931762)
• a model of CagA-directed REG3gamma expression in gastric epithelial cells via activation of the IL-11/gp130/STAT3 pathway (PMID:22312430)
• Proteasome-dependent degradation of Smad7 is critical for lung cancer metastasis. (PMID:31767934)
• Role of oncogenic REGgamma in cancer. (PMID:32935661)
• Myocardial Accumulations of Reg3A, Reg3gamma and Oncostatin M Are Associated with the Formation of Granulomata in Patients with Cardiac Sarcoidosis. (PMID:33923774)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-125e6.11	ENSDARG00000025783
danio_rerio	zgc:172053	ENSDARG00000038321
danio_rerio	si:dkey-241l7.6	ENSDARG00000041248
danio_rerio	si:dkey-9i23.4	ENSDARG00000051993
danio_rerio	lectin	ENSDARG00000055833
danio_rerio	si:ch211-125e6.5	ENSDARG00000069381
danio_rerio	si:dkey-241l7.3	ENSDARG00000086956
danio_rerio	si:dkey-241l7.5	ENSDARG00000088989
danio_rerio	si:dkey-241l7.4	ENSDARG00000089478
danio_rerio	si:ch211-125e6.12	ENSDARG00000092090
danio_rerio	si:dkey-9i23.5	ENSDARG00000092459
danio_rerio	si:ch211-125e6.14	ENSDARG00000094183
danio_rerio	si:ch211-125e6.13	ENSDARG00000094370
danio_rerio	si:dkey-241l7.2	ENSDARG00000105335
caenorhabditis_elegans		WBGENE00012621
caenorhabditis_elegans		WBGENE00016912
caenorhabditis_elegans		WBGENE00019328
caenorhabditis_elegans		WBGENE00019914
caenorhabditis_elegans		WBGENE00020585

Paralogs (5): REG1A (ENSG00000115386), REG4 (ENSG00000134193), REG3A (ENSG00000172016), REG1B (ENSG00000172023), CLEC19A (ENSG00000261210)

Protein

Protein identifiers

Regenerating islet-derived protein 3-gamma — Q6UW15 (reviewed: Q6UW15)

Alternative names: Pancreatitis-associated protein 1B, Pancreatitis-associated protein IB, Regenerating islet-derived protein III-gamma

All UniProt accessions (1): Q6UW15

UniProt curated annotations — full annotation on UniProt →

Function. Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan. Restricts bacterial colonization of the intestinal epithelial surface and consequently limits activation of adaptive immune responses by the microbiota. Acts as a hormone in response to different stimuli like anti-inflammatory signals, such as IL17A, or gut microbiome. Is secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways. Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury. In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF. Induced by IL22 in lung epithelial cells, inhibits cytokine production and regulates allergic airway inflammation. Induced in small intestine by inulin-enriched diet and Lactobacillus gasseri enriched microbiome, plays a role in the improvement of gut barrier function, the regulation of energy balance and glucose levels. Modulates microbiota composition in duodenal contents. Produced by nociceptor in response to endotoxins, prevents endotoxic death by targeting kynurenine pathway in microglia. Has bacteriostatic activity. Has bactericidal activity against L.monocytogenes and methicillin-resistant S.aureus.

Subunit / interactions. Forms a hexameric membrane-permeabilizing oligomeric pore on membrane phospholipids. The hexamer is formed by three dimers related by helical symmetry. Forms filaments, filamentation traps pore complexes and limits damage to host cells. Interacts with EXTL3.

Subcellular location. Secreted. Cytoplasm.

Tissue specificity. Predominantly expressed in pancreas, where it may be restricted to exocrine pancreas. Moderate expression levels in testis and weak in heart, kidney and placenta.

Post-translational modifications. Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.

Activity regulation. Lipopolysaccharide inhibits pore-forming activity, explaining why is bactericidal for Gram-positive but not Gram-negative bacteria.

Domain organisation. The EPN motif is essential for recognition of the peptidoglycan carbohydrate backbone and for efficient bacterial killing with Glu-114 playing a key role in peptidoglycan binding and bactericidal activity.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UW15-1	1	yes
Q6UW15-2	2

RefSeq proteins (3): NP_001008388, NP_001256969, NP_940850 (=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
IPR018378	C-type_lectin_CS	Conserved_site
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059

UniProt features (15 total): disulfide bond 3, binding site 3, chain 2, signal peptide 1, splice variant 1, sequence conflict 1, propeptide 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UW15-F1	89.50	0.77

Functional residue map

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

Ligand- & substrate-binding residues (3): 107; 121; 145

Disulfide bonds (3): 40–51, 68–171, 146–163

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 123 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_KERATINOCYTE_PROLIFERATION, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_MYD88_DEPENDENT_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_WOUND_HEALING, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (10): MyD88-dependent toll-like receptor signaling pathway (GO:0002755), acute-phase response (GO:0006953), positive regulation of cell population proliferation (GO:0008284), positive regulation of keratinocyte proliferation (GO:0010838), response to peptide hormone (GO:0043434), negative regulation of keratinocyte differentiation (GO:0045617), defense response to Gram-positive bacterium (GO:0050830), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), positive regulation of wound healing (GO:0090303), inflammatory response (GO:0006954)

GO Molecular Function (5): signaling receptor activity (GO:0038023), peptidoglycan binding (GO:0042834), metal ion binding (GO:0046872), oligosaccharide binding (GO:0070492), carbohydrate binding (GO:0030246)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
toll-like receptor signaling pathway	1
acute inflammatory response	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
positive regulation of epithelial cell proliferation	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
keratinocyte differentiation	1
negative regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
negative regulation of multicellular organismal process	1
defense response to bacterium	1
antimicrobial humoral response	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
defense response	1
molecular transducer activity	1
glycosaminoglycan binding	1
cation binding	1
carbohydrate binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REG3G	IL22	Q9GZX6	864
REG3G	IL22RA2	Q969J5	756
REG3G	MUC1	P13931	625
REG3G	MUC2	Q02817	604
REG3G	IL17A	Q16552	598
REG3G	MYD88	P78397	583
REG3G	IL22RA1	Q8N6P7	582
REG3G	NOD2	Q9HC29	574
REG3G	LCN2	P30150	573
REG3G	TLR5	O60602	571
REG3G	OCLN	Q16625	541
REG3G	FFAR2	O15552	540
REG3G	IFNG	P01579	533
REG3G	IL1B	P01584	533
REG3G	S100A7	P31151	528

IntAct

0 interactions, top by confidence:

BioGRID (2): REG3G (Negative Genetic), HMGB1P1 (Affinity Capture-MS)

ESM2 similar proteins: A1XXJ9, A3FM55, A7X3Z4, A7X3Z7, A7X413, B4XSY7, B4XSZ1, B4XT00, B4XT01, B4XT02, B4XT03, B4XT08, D1MGU0, E2DQZ6, I7JUQ0, J3S3U6, O09037, O09049, P0DM38, P10758, P23132, P23807, P25031, P35230, P35231, P42854, P43137, Q06141, Q08731, Q09GJ8, Q09GK0, Q38L02, Q5FZI6, Q696W1, Q6T7B5, Q6T7B7, Q6TPH0, Q6UW15, Q71RQ7, Q71RR1

Diamond homologs: A1XXJ9, A3FM55, A7X3W1, A7X3W6, A7X3X0, A7X3X3, A7X3X8, A7X3Y2, A7X3Y6, A7X3Z0, A7X3Z4, A7X3Z7, A7X401, A7X406, A7X409, A7X413, B0VXV0, B0VXV1, B5U6Y6, C6JUN9, D1MGU0, D2YVH7, D2YVI2, D2YVJ6, D2YVJ8, D2YVK1, D2YVK5, D2YW40, D8VNS6, I7ICN3, J3S3U6, J3SBP0, O93427, P05451, P07439, P0DL30, P0DM36, P0DM38, P0DM39, P0DM53

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

585 predictions. Top by Δscore:

Variant	Effect	Δscore
2:79026706:A:AG	acceptor_gain	1.0000
2:79026710:CA:C	acceptor_loss	1.0000
2:79026711:A:AG	acceptor_gain	1.0000
2:79026711:A:T	acceptor_loss	1.0000
2:79026712:G:GG	acceptor_gain	1.0000
2:79026712:GGT:G	acceptor_gain	1.0000
2:79026772:GCC:G	donor_gain	1.0000
2:79026829:GAT:G	donor_gain	1.0000
2:79026830:AT:A	donor_gain	1.0000
2:79026832:G:GG	donor_gain	1.0000
2:79027801:CTATA:C	acceptor_loss	1.0000
2:79027802:TATA:T	acceptor_loss	1.0000
2:79027803:ATAG:A	acceptor_gain	1.0000
2:79027804:TAG:T	acceptor_loss	1.0000
2:79027805:A:AC	acceptor_loss	1.0000
2:79027805:AG:A	acceptor_gain	1.0000
2:79027805:AGG:A	acceptor_gain	1.0000
2:79027806:G:T	acceptor_loss	1.0000
2:79027806:GG:G	acceptor_gain	1.0000
2:79027806:GGG:G	acceptor_gain	1.0000
2:79027806:GGGCT:G	acceptor_gain	1.0000
2:79026707:C:G	acceptor_gain	0.9900
2:79026711:AG:A	acceptor_gain	0.9900
2:79026711:AGGT:A	acceptor_gain	0.9900
2:79026712:GG:G	acceptor_gain	0.9900
2:79026712:GGTG:G	acceptor_gain	0.9900
2:79026712:GGTGA:G	acceptor_gain	0.9900
2:79026827:CAGAT:C	donor_gain	0.9900
2:79026828:AGAT:A	donor_gain	0.9900
2:79026829:GATG:G	donor_gain	0.9900

AlphaMissense

1139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:79027872:G:C	W133C	0.997
2:79027872:G:T	W133C	0.997
2:79028222:G:C	W158C	0.997
2:79028222:G:T	W158C	0.997
2:79027839:G:C	W122C	0.996
2:79027839:G:T	W122C	0.996
2:79027833:G:C	W120C	0.995
2:79027833:G:T	W120C	0.995
2:79026819:G:C	W61C	0.994
2:79026819:G:T	W61C	0.994
2:79028220:T:A	W158R	0.994
2:79028220:T:C	W158R	0.994
2:79027147:G:C	W103C	0.993
2:79027147:G:T	W103C	0.993
2:79027909:T:A	C146S	0.992
2:79027910:G:C	C146S	0.992
2:79028259:T:A	C171S	0.991
2:79028260:G:C	C171S	0.991
2:79028235:T:A	C163S	0.990
2:79028236:G:C	C163S	0.990
2:79027837:T:A	W122R	0.989
2:79027837:T:C	W122R	0.989
2:79027040:T:A	C68S	0.988
2:79027041:G:C	C68S	0.988
2:79026826:G:C	A64P	0.987
2:79028236:G:A	C163Y	0.986
2:79027041:G:A	C68Y	0.985
2:79027910:G:A	C146Y	0.985
2:79028211:T:C	F155L	0.985
2:79028213:T:A	F155L	0.985

dbSNP variants (sampled 300 via entrez): RS1000037572 (2:79024310 G>T), RS1000494503 (2:79027916 G>A), RS1001059705 (2:79024507 C>T), RS1001676543 (2:79025222 A>G), RS1002127277 (2:79025492 A>G), RS1003752544 (2:79026550 T>C), RS1003942032 (2:79026465 T>C), RS1004345022 (2:79028859 T>C), RS1005027812 (2:79024992 C>T), RS1005617018 (2:79027553 A>G), RS1008354073 (2:79023818 T>C), RS1008927885 (2:79025438 T>C), RS1010186021 (2:79024358 C>A), RS1010998646 (2:79025503 AGGGTG>A), RS1011582249 (2:79026925 T>C)

Disease associations

OMIM: gene MIM:609933 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002238_2	Contrast sensitivity	1.000000e-07
GCST004575_5	Acute insulin response	3.000000e-08
GCST005951_41	Body mass index	4.000000e-08
GCST006585_1639	Blood protein levels	9.000000e-63
GCST009698_79	Metabolite levels	2.000000e-08
GCST012311_29	Schizophrenia x sex interaction	5.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005419	contrast sensitivity measurement
EFO:0006831	acute insulin response measurement
EFO:0004340	body mass index
EFO:0010118	sphingomyelin measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
clothianidin	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Isoproterenol	decreases expression	1

Clinical trials (associated diseases)

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