REG1B

Summary

REG1B (regenerating family member 1 beta, HGNC:9952) is a protein-coding gene on chromosome 2p12, encoding Lithostathine-1-beta (P48304). Might act as an inhibitor of spontaneous calcium carbonate precipitation.

This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III and IV based on the primary structures of the encoded proteins. This gene encodes a protein secreted by the exocrine pancreas that is highly similar to the REG1A protein. The related REG1A protein is associated with islet cell regeneration and diabetogenesis, and may be involved in pancreatic lithogenesis. Reg family members REG1A, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication.

Source: NCBI Gene 5968 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_006507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9952
Approved symbol	REG1B
Name	regenerating family member 1 beta
Location	2p12
Locus type	gene with protein product
Status	Approved
Aliases	REGL, PSPS2, REGH, REGI-BETA
Ensembl gene	ENSG00000172023
Ensembl biotype	protein_coding
OMIM	167771
Entrez	5968

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 retained_intron

ENST00000305089, ENST00000454188, ENST00000469052, ENST00000476554, ENST00000479258, ENST00000956726

RefSeq mRNA: 1 — MANE Select: NM_006507 NM_006507

CCDS: CCDS1963

Canonical transcript exons

ENST00000305089 — 6 exons

Exon	Start	End
ENSE00001666759	79085023	79085283
ENSE00001901247	79087959	79087993
ENSE00002502476	79086367	79086504
ENSE00002516851	79085492	79085603
ENSE00003552926	79087549	79087658
ENSE00003609971	79086812	79086930

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 99.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.9574 / max 11810.6639, expressed in 17 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29321	6.1438	15
29322	0.7902	5
29319	0.0234	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.95	gold quality
body of pancreas	UBERON:0001150	99.95	gold quality
type B pancreatic cell	CL:0000169	99.94	gold quality
ileal mucosa	UBERON:0000331	99.75	gold quality
pancreas	UBERON:0001264	99.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.00	gold quality
epithelial cell of pancreas	CL:0000083	92.11	gold quality
small intestine	UBERON:0002108	89.48	gold quality
vermiform appendix	UBERON:0001154	80.60	gold quality
duodenum	UBERON:0002114	79.18	gold quality
apex of heart	UBERON:0002098	78.94	gold quality
right coronary artery	UBERON:0001625	77.93	gold quality
caecum	UBERON:0001153	77.36	gold quality
right uterine tube	UBERON:0001302	77.18	gold quality
ectocervix	UBERON:0012249	76.53	gold quality
endocervix	UBERON:0000458	74.34	gold quality
left uterine tube	UBERON:0001303	74.11	gold quality
lower esophagus mucosa	UBERON:0035834	73.87	gold quality
right adrenal gland cortex	UBERON:0035827	73.82	gold quality
mucosa of stomach	UBERON:0001199	73.00	gold quality
right adrenal gland	UBERON:0001233	72.38	gold quality
pancreatic ductal cell	CL:0002079	71.03	silver quality
right ovary	UBERON:0002118	70.73	gold quality
body of stomach	UBERON:0001161	70.05	gold quality
right lobe of liver	UBERON:0001114	68.82	gold quality
intestine	UBERON:0000160	67.70	gold quality
transverse colon	UBERON:0001157	67.69	gold quality
jejunal mucosa	UBERON:0000399	67.01	gold quality
fundus of stomach	UBERON:0001160	65.67	gold quality
left adrenal gland	UBERON:0001234	65.46	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	27979.93
E-MTAB-5061	yes	25713.93
E-HCAD-31	yes	24121.71
E-ENAD-27	yes	16335.36
E-GEOD-125970	yes	67.91
E-GEOD-81608	yes	13.03
E-GEOD-83139	no	2.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, HOXB2

miRNA regulators (miRDB)

32 targeting REG1B, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-552-3P	96.68	64.12	1026

Literature-anchored findings (GeneRIF, showing 10)

• did not find any association between abnormalities of either reg1 alpha or reg1 beta gene with type 1 diabetes mellitus, fibrocalculous pancreatopathy, or type 2 diabetes mellitus (PMID:11796176)
• This finding suggests that REG I may act through IL-6 to exert effects on squamous esophageal cancer cell biology. (PMID:20056108)
• REG 1A and REG 1B were upregulated during amebiasis and may function to protect the intestinal epithelium from parasite-induced apoptosis. (PMID:21586335)
• The expression of MK-1 and/or RegIV might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma (PMID:22018336)
• Immunohistochemistry against known cell-type markers on serial sections has localised the expression of REGs to metaplastic Paneth cells (REG1A, REG1B and REG3A) and enteroendocrine cells (REG4), with a marked expansion of expression during inflammation. (PMID:23519454)
• Higher REG1B stool concentrations at month 3 were significantly and independently associated with a growth shortfall in Bangladeshi and Peruvian children. (PMID:23553156)
• Additional serum biomarkers, particularly SYCN and REG1B, when combined with CA19.9, show promise as improved diagnostic indicators of pancreatic cancer, which therefore warrants further validation. (PMID:24007603)
• the expression of REG Ialpha and REG Ibeta may be upregulated in human beta cells under inflammatory conditions through the JAK/STAT pathway (PMID:25767811)
• REG-I is expressed in head and neck squamous cell carcinoma and is associated with a longer survival status. (PMID:27539087)
• Faecal regenerating 1B protein concentration is not associated with child growth in rural Malawi. (PMID:33112481)

Cross-species orthologs

26 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
mus_musculus	Reg3g	ENSMUSG00000030017
mus_musculus	Reg3d	ENSMUSG00000068341
mus_musculus	Reg3b	ENSMUSG00000071356
mus_musculus	Reg3a	ENSMUSG00000079516
rattus_norvegicus	Reg3b	ENSRNOG00000006151
rattus_norvegicus	Reg3a	ENSRNOG00000006360
rattus_norvegicus	Reg3g	ENSRNOG00000006579
caenorhabditis_elegans		WBGENE00012621
caenorhabditis_elegans		WBGENE00016912
caenorhabditis_elegans		WBGENE00019328
caenorhabditis_elegans		WBGENE00019914
caenorhabditis_elegans		WBGENE00020585

Paralogs (5): REG1A (ENSG00000115386), REG4 (ENSG00000134193), REG3G (ENSG00000143954), REG3A (ENSG00000172016), CLEC19A (ENSG00000261210)

Protein

Protein identifiers

Lithostathine-1-beta — P48304 (reviewed: P48304)

Alternative names: Pancreatic stone protein 2, Regenerating islet-derived protein 1-beta, Regenerating protein I beta

All UniProt accessions (3): P48304, H7BZ24, Q6ICS1

UniProt curated annotations — full annotation on UniProt →

Function. Might act as an inhibitor of spontaneous calcium carbonate precipitation. May be associated with neuronal sprouting in brain, and with brain and pancreas regeneration.

Subcellular location. Secreted.

Post-translational modifications. All O-linked glycans consist of Gal-GlcNAc-Gal-GalNAc tetrasaccharide core and get elongated (microheterogeneity).

RefSeq proteins (1): NP_006498* (*=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 (8 total): disulfide bond 3, signal peptide 1, chain 1, domain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48304-F1	89.58	0.78

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): 36–47, 64–162, 137–154

Glycosylation sites (1): 27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOMF_GROWTH_FACTOR_ACTIVITY, MODULE_75, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, MODULE_379, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MODULE_410, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_HORMONE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, MODULE_88, chr2p12, MODULE_242

GO Biological Process (3): positive regulation of cell population proliferation (GO:0008284), response to peptide hormone (GO:0043434), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844)

GO Molecular Function (5): signaling receptor activity (GO:0038023), peptidoglycan binding (GO:0042834), oligosaccharide binding (GO:0070492), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
antimicrobial humoral response	1
molecular transducer activity	1
glycosaminoglycan binding	1
carbohydrate binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REG1B	ZC3H12A	Q5D1E8	905
REG1B	CLEC1A	Q8NC01	711
REG1B	DEFA6	Q01524	665
REG1B	DEFA5	Q01523	619
REG1B	TFF1	P04155	583
REG1B	SYCN	Q0VAF6	564
REG1B	DUOXA2	Q1HG44	560
REG1B	LYVE1	Q9Y5Y7	491
REG1B	DUOX2	Q9NRD8	491
REG1B	CLPS	P04118	485
REG1B	LCN2	P30150	473
REG1B	MUC1	P13931	450
REG1B	DUOXA1	Q1HG43	449
REG1B	PNMA5	Q96PV4	448
REG1B	REG3A	Q06141	438

IntAct

7 interactions, top by confidence:

A	B	Type	Score
REG1B	REG1A	psi-mi:“MI:0915”(physical association)	0.560
REG1B	REG1A	psi-mi:“MI:0914”(association)	0.560
REG1A	REG1B	psi-mi:“MI:0914”(association)	0.560
CRELD2	REG1B	psi-mi:“MI:0915”(physical association)	0.370
REG1B	BAG6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): REG1A (Affinity Capture-MS), REG1B (Co-fractionation), REG1A (Affinity Capture-MS), BAG6 (Two-hybrid), REG1B (Affinity Capture-MS), NAA25 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), REG1A (Affinity Capture-MS), BAG6 (Two-hybrid)

ESM2 similar proteins: A1XXJ9, A7X3X0, A7X3X3, A7X3X8, A7X3Y2, B5U6Y6, D2YVH7, D2YVJ8, D2YVK5, D8VNS6, I7ICN3, O09037, O09049, O93426, O93427, P05451, P0DM38, P10758, P23132, P23807, P25031, P35230, P35231, P42854, P43137, P48304, P81112, P81114, Q06141, Q08731, Q09GJ8, Q09GK0, Q56EB0, Q5FZI6, Q68AX7, Q6TPG9, Q6UW15, Q6X5S0, Q6X5S1, Q6X5S4

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

491 predictions. Top by Δscore:

Variant	Effect	Δscore
2:79085604:C:CC	acceptor_gain	1.0000
2:79086362:CTGA:C	donor_loss	1.0000
2:79086364:GAC:G	donor_loss	1.0000
2:79086500:TAGAG:T	acceptor_gain	1.0000
2:79086501:AGAG:A	acceptor_gain	1.0000
2:79086502:GAG:G	acceptor_gain	1.0000
2:79086503:AG:A	acceptor_gain	1.0000
2:79086504:GC:G	acceptor_loss	1.0000
2:79086505:C:A	acceptor_loss	1.0000
2:79086505:C:CC	acceptor_gain	1.0000
2:79086508:T:TC	acceptor_gain	1.0000
2:79086801:T:A	donor_gain	1.0000
2:79086806:A:AC	donor_gain	1.0000
2:79086807:C:CC	donor_gain	1.0000
2:79086807:CTCA:C	donor_gain	1.0000
2:79086808:TCACA:T	donor_loss	1.0000
2:79086809:CA:C	donor_loss	1.0000
2:79086810:A:AC	donor_gain	1.0000
2:79086810:ACAT:A	donor_gain	1.0000
2:79086811:C:CA	donor_gain	1.0000
2:79086811:C:CG	donor_loss	1.0000
2:79086811:CA:C	donor_gain	1.0000
2:79086811:CAT:C	donor_gain	1.0000
2:79086811:CATC:C	donor_gain	1.0000
2:79086811:CATCT:C	donor_gain	1.0000
2:79086926:CTGGC:C	acceptor_gain	1.0000
2:79086927:TGGC:T	acceptor_gain	1.0000
2:79086929:GC:G	acceptor_gain	1.0000
2:79086930:CC:C	acceptor_gain	1.0000
2:79086931:C:CC	acceptor_gain	1.0000

AlphaMissense

1100 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:79085553:C:A	W124C	1.000
2:79085553:C:G	W124C	1.000
2:79085270:C:A	W149C	0.999
2:79085270:C:G	W149C	0.999
2:79085586:C:A	W113C	0.999
2:79085586:C:G	W113C	0.999
2:79085592:C:A	W111C	0.999
2:79085592:C:G	W111C	0.999
2:79086391:C:A	W99C	0.999
2:79086391:C:G	W99C	0.999
2:79086497:C:G	C64S	0.999
2:79086498:A:T	C64S	0.999
2:79086817:C:G	A60P	0.999
2:79086824:C:A	W57C	0.999
2:79086824:C:G	W57C	0.999
2:79085232:C:G	C162S	0.998
2:79085233:A:T	C162S	0.998
2:79085237:A:C	F160L	0.998
2:79085237:A:T	F160L	0.998
2:79085239:A:G	F160L	0.998
2:79085272:A:G	W149R	0.998
2:79085272:A:T	W149R	0.998
2:79086496:G:C	C64W	0.998
2:79086497:C:T	C64Y	0.998
2:79085232:C:T	C162Y	0.997
2:79085555:A:G	W124R	0.997
2:79085555:A:T	W124R	0.997
2:79085594:A:G	W111R	0.997
2:79085594:A:T	W111R	0.997
2:79086383:A:G	L102P	0.997

dbSNP variants (sampled 300 via entrez): RS1000494498 (2:79087276 A>G), RS1000609081 (2:79087495 A>C), RS1000831770 (2:79085101 T>C,G), RS1001164529 (2:79085149 T>A,C,G), RS1002165266 (2:79086376 G>A), RS1002671177 (2:79084746 C>G), RS1003204506 (2:79088683 G>T), RS1005198264 (2:79086009 C>T), RS1005914963 (2:79084722 C>T), RS1005996069 (2:79089585 G>A), RS1006196217 (2:79087027 C>T), RS1007611123 (2:79086069 T>A,C), RS1008494538 (2:79087257 C>A,G), RS1009758087 (2:79086357 G>T), RS1010053046 (2:79086080 A>G)

Disease associations

OMIM: gene MIM:167771 | 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
GCST002238_2	Contrast sensitivity	1.000000e-07
GCST005951_41	Body mass index	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005419	contrast sensitivity measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
5-iodotubercidin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	decreases reaction, decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Smoke	decreases reaction, decreases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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