RETNLB

Summary

RETNLB (resistin like beta, HGNC:20388) is a protein-coding gene on chromosome 3q13.13, encoding Resistin-like beta (Q9BQ08). Probable hormone.

Predicted to enable hormone activity. Involved in epithelial cell proliferation. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 84666 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_032579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20388
Approved symbol	RETNLB
Name	resistin like beta
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Aliases	HXCP2, FIZZ2, RELMb
Ensembl gene	ENSG00000163515
Ensembl biotype	protein_coding
OMIM	605645
Entrez	84666

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295755, ENST00000482939

RefSeq mRNA: 2 — MANE Select: NM_032579 NM_001412183, NM_032579

CCDS: CCDS2953

Canonical transcript exons

ENST00000295755 — 3 exons

Exon	Start	End
ENSE00001176490	108755638	108755905
ENSE00001176498	108757059	108757410
ENSE00003540174	108756508	108756588

Expression profiles

Bgee: expression breadth broad, 66 present calls, max score 98.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0860 / max 54.7414, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43676	0.0860	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.31	gold quality
rectum	UBERON:0001052	96.86	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.10	gold quality
mucosa of transverse colon	UBERON:0004991	95.44	gold quality
colonic mucosa	UBERON:0000317	88.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.68	gold quality
transverse colon	UBERON:0001157	84.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.73	gold quality
small intestine	UBERON:0002108	81.08	gold quality
duodenum	UBERON:0002114	77.03	gold quality
intestine	UBERON:0000160	73.10	gold quality
jejunal mucosa	UBERON:0000399	71.56	gold quality
large intestine	UBERON:0000059	71.19	gold quality
colon	UBERON:0001155	70.14	gold quality
colonic epithelium	UBERON:0000397	68.09	gold quality
kidney epithelium	UBERON:0004819	67.00	gold quality
vermiform appendix	UBERON:0001154	66.25	gold quality
caecum	UBERON:0001153	65.29	gold quality
cerebellar vermis	UBERON:0004720	62.86	gold quality
parotid gland	UBERON:0001831	61.55	gold quality
jejunum	UBERON:0002115	60.93	silver quality
tibialis anterior	UBERON:0001385	60.32	silver quality
vena cava	UBERON:0004087	60.31	gold quality
pancreatic ductal cell	CL:0002079	60.18	silver quality
tibia	UBERON:0000979	59.10	gold quality
left ventricle myocardium	UBERON:0006566	56.88	gold quality
deltoid	UBERON:0001476	56.65	gold quality
endothelial cell	CL:0000115	56.55	gold quality
oocyte	CL:0000023	56.25	silver quality
epithelial cell of pancreas	CL:0000083	54.67	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CDX2, CEBPG, HAND2, STAT6

miRNA regulators (miRDB)

6 targeting RETNLB, 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-556-3P	99.74	68.75	1203
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6830-3P	98.62	68.07	1760

Literature-anchored findings (GeneRIF, showing 22)

• Supernatant from COS cells transfected with the CCRG (RETNLB) expression vector stimulated proliferation of colon cancer cells, which supports the growth factor nature of the RETNLB gene. (PMID:12224133)
• High levels of RELMbeta can be detected in the stool of mice and humans, where it exists as a homodimer under nonreducing conditions. (PMID:14598255)
• Of the 80 colon cancer patients studied, 65 (81.25%) tested positive for RELM beta, mainly in the cytoplasm of colon mucosa. (PMID:18594973)
• Results suggest that RELM-beta may be involved in the development of scleroderma-associated pulmonary hypertension. (PMID:19251945)
• Gastric cncer patients showing positive RELMbeta expression had a significantly longer overall survival than those with negative expression (P = 0.001). (PMID:19967544)
• High RELMbeta is associated with colorectal cancer. (PMID:21094111)
• FIZZ2 is highly induced in lungs of human patients with idiopathic pulmonary fibrosis. (PMID:21602491)
• RELM-beta has the potential to contribute to airway remodelling in diseases such as asthma by acting on epithelial cells to increase proliferation, mucin and growth factor production, at least partly via ERK/MAPK-PI3K/Akt signalling pathways. (PMID:21828035)
• Data show that over-expression of RELMbeta abolishes the invasion, metastasis and angiogenesis of gastric cancer cells in vitro. (PMID:22371635)
• Epithelial cell derived Fizz1 transgene is sufficient to increase bone-marrow derived dendritic cells in the lungs. (PMID:22726462)
• RELM-beta may play an important role not only in animal models of airway remodelling, but also in human airway pathology. (PMID:22758223)
• It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMalpha induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness. (PMID:23392702)
• RELMbeta is abundantly expressed in foam cells within plaques and contributes to atherosclerosis development via lipid accumulation and inflammatory facilitation. (PMID:23702657)
• RELMbeta levels were increased in Abdominal aortic aneurysm patients in the serum and in the aortic tissue. Increased RELMbeta levels may be involved in the pathogenesis of AAA formation and progress. (PMID:25479529)
• elevated RELM-beta expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins. (PMID:25545115)
• The data demonstrated that RELM-a is a promising novel biomarker of angiogenesis in patients with gastric cancer. (PMID:25937206)
• RELMbeta-overexpression can facilitate invasion and migration of gastric carcinoma cells. (PMID:27001185)
• Investigated the function and mechanism of RELM-beta in TGF-beta1-induced endothelium-mesenchymal transition in endothelial cell lines. We found that TGF-beta1 stimulation significantly upregulated RELM-beta expression; RELM-beta knockdown could attenuate TGF-beta1-induced cell proliferation and migration of endothelial cell lines. (PMID:30120989)
• Plasma RELMbeta levels in necrotizing enterocolitis group were significantly higher than control group. (PMID:30799148)
• Helicobacter pylori Infection Facilitates the Expression of Resistin-like Molecule Beta in Gastric Carcinoma and Precursor Lesions. (PMID:32166670)
• Investigating resistin like beta (RETNLB) as a tumor promoter for oral squamous cell carcinoma. (PMID:34158059)
• Resistin-like beta reduction is associated to low survival rate and is downregulated by adjuvant therapy in colorectal cancer patients. (PMID:36707698)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Retnlb	ENSMUSG00000022650
mus_musculus	Retnlg	ENSMUSG00000022651
mus_musculus	Retnla	ENSMUSG00000061100
rattus_norvegicus	Retnlg	ENSRNOG00000001943
rattus_norvegicus	Retnla	ENSRNOG00000001955
rattus_norvegicus	Retnlb	ENSRNOG00000032187

Paralogs (1): RETN (ENSG00000104918)

Protein

Protein identifiers

Resistin-like beta — Q9BQ08 (reviewed: Q9BQ08)

Alternative names: Colon and small intestine-specific cysteine-rich protein, Colon carcinoma-related gene protein, Cysteine-rich secreted protein A12-alpha-like 1, Cysteine-rich secreted protein FIZZ2, RELMbeta

All UniProt accessions (1): Q9BQ08

UniProt curated annotations — full annotation on UniProt →

Function. Probable hormone.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Expressed only in the gastrointestinal tract, particularly the colon.

Similarity. Belongs to the resistin/FIZZ family.

RefSeq proteins (2): NP_001399112, NP_115968* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009714	RELM	Family
IPR036262	Resistin-like_sf	Homologous_superfamily

Pfam: PF06954

UniProt features (9 total): disulfide bond 6, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ08-F1	85.48	0.55

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 (6): 25, 55–108, 67–107, 76–93, 78–95, 82–97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GCANCTGNY_MYOD_Q6, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, SABATES_COLORECTAL_ADENOMA_SIZE_DN, CAGCTG_AP4_Q5, MARTINEZ_RB1_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, NF1_Q6_01, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, TGGNNNNNNKCCAR_UNKNOWN, MCDOWELL_ACUTE_LUNG_INJURY_UP, GOBP_EPITHELIAL_CELL_PROLIFERATION, VECCHI_GASTRIC_CANCER_EARLY_DN, GOMF_SIGNALING_RECEPTOR_BINDING, ZHENG_IL22_SIGNALING_UP, GOMF_HORMONE_ACTIVITY

GO Biological Process (2): epithelial cell proliferation (GO:0050673), signal transduction (GO:0007165)

GO Molecular Function (1): hormone activity (GO:0005179)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1623 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RETNLB	TLR4	O00206	991
RETNLB	CAP1	Q01518	937
RETNLB	ADIPOQ	Q15848	926
RETNLB	LEP	P41159	924
RETNLB	NAMPT	P43490	880
RETNLB	DCN	P07585	879
RETNLB	INS	P01308	852
RETNLB	ARG1	P05089	836
RETNLB	IL6	P05231	822
RETNLB	PPARG	P37231	782
RETNLB	TNF	P01375	780
RETNLB	ITLN1	Q8WWA0	772
RETNLB	RARRES2	Q99969	771
RETNLB	SERPINE1	P05121	767
RETNLB	CRP	P02741	764

IntAct

3 interactions, top by confidence:

A	B	Type	Score
RAB27A	GTPBP1	psi-mi:“MI:0914”(association)	0.350
RETNLB	PLXNA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): RETNLB (Synthetic Growth Defect), LONP2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), CRY1 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), WDR54 (Affinity Capture-MS), VHL (Affinity Capture-MS), TGFB1 (Affinity Capture-MS), MICA (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), EMILIN2 (Affinity Capture-MS), RETNLB (Affinity Capture-MS)

ESM2 similar proteins: A0A172M477, A0A346CED7, A1L3I3, A2A9G7, A2BDG0, A2BDG5, A2BDG9, A2CEX1, A2RV66, A6QQ93, C1J5M5, C1J5M6, C1J5M7, D4A540, E2IH92, P01286, P09916, P0C7I1, P0DTJ8, P54615, P56529, P58239, P58844, P80957, P86045, P86546, P86547, Q0H293, Q14CH0, Q16655, Q1JPW9, Q32KM8, Q5CZ51, Q5RD34, Q5RJX2, Q5VUB5, Q6P995, Q6UWW9, Q80ZA7, Q86DU6

Diamond homologs: G3V686, Q762I5, Q8K426, Q99P85, Q99P86, Q99P87, Q9BQ08, Q9EP95, Q9HD89

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

399 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108757076:T:TA	donor_gain	1.0000
3:108756587:CT:C	acceptor_gain	0.9900
3:108756588:TCTGA:T	acceptor_gain	0.9900
3:108756589:C:CC	acceptor_gain	0.9900
3:108756593:G:GC	acceptor_gain	0.9900
3:108757054:GTTA:G	donor_loss	0.9900
3:108757057:A:T	donor_loss	0.9900
3:108757123:C:CA	donor_gain	0.9900
3:108756585:TACT:T	acceptor_gain	0.9800
3:108757124:C:A	donor_gain	0.9800
3:108755904:CC:C	acceptor_gain	0.9600
3:108755905:CC:C	acceptor_gain	0.9600
3:108756593:G:C	acceptor_gain	0.9600
3:108757057:A:AC	donor_gain	0.9600
3:108757058:C:CC	donor_gain	0.9600
3:108757090:AT:A	donor_gain	0.9600
3:108755903:TCC:T	acceptor_gain	0.9500
3:108755904:CCC:C	acceptor_gain	0.9500
3:108756585:TACTC:T	acceptor_gain	0.9500
3:108756586:ACT:A	acceptor_gain	0.9500
3:108756586:ACTCT:A	acceptor_gain	0.9500
3:108756587:CTC:C	acceptor_gain	0.9500
3:108756588:TC:T	acceptor_loss	0.9500
3:108756589:CT:C	acceptor_loss	0.9500
3:108756590:T:A	acceptor_loss	0.9500
3:108756584:GTACT:G	acceptor_gain	0.9400
3:108756589:C:G	acceptor_gain	0.9400
3:108756851:C:CT	donor_gain	0.9400
3:108756852:T:TT	donor_gain	0.9400
3:108757046:CCCAG:C	donor_gain	0.9400

AlphaMissense

722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:108755808:C:A	W102C	0.935
3:108755808:C:G	W102C	0.935
3:108755859:C:A	W85C	0.933
3:108755859:C:G	W85C	0.933
3:108756545:A:C	S57R	0.858
3:108756545:A:T	S57R	0.858
3:108756547:T:G	S57R	0.858
3:108755861:A:G	W85R	0.837
3:108755861:A:T	W85R	0.837
3:108755797:C:G	R106P	0.825
3:108755879:C:A	G79C	0.813
3:108755791:C:G	C108S	0.804
3:108755792:A:T	C108S	0.804
3:108755794:C:G	C107S	0.804
3:108755795:A:T	C107S	0.804
3:108755887:C:G	C76S	0.804
3:108755888:A:T	C76S	0.804
3:108755885:C:G	A77P	0.795
3:108755810:A:G	W102R	0.782
3:108755810:A:T	W102R	0.782
3:108755800:G:T	A105D	0.778
3:108755878:C:T	G79D	0.777
3:108755869:C:G	C82S	0.773
3:108755870:A:T	C82S	0.773
3:108756552:C:G	C55S	0.768
3:108756553:A:T	C55S	0.768
3:108755888:A:G	C76R	0.761
3:108755881:C:T	C78Y	0.759
3:108755829:G:C	C95W	0.758
3:108755836:C:G	C93S	0.755

dbSNP variants (sampled 300 via entrez): RS1001007992 (3:108756229 T>C,G), RS1001863624 (3:108755663 C>A,G,T), RS1003019335 (3:108759097 T>C), RS1003481156 (3:108758758 G>A,C,T), RS1003860303 (3:108758214 G>T), RS1005533508 (3:108756890 C>A,G,T), RS1007101713 (3:108756442 C>A), RS1008782536 (3:108758288 G>C), RS1010041146 (3:108756883 A>G), RS1010668754 (3:108757447 G>T), RS1010767266 (3:108757840 C>T), RS1011658405 (3:108759124 T>C), RS1011873210 (3:108755443 A>AC,AG,AT), RS1012483676 (3:108759216 A>G), RS1014980902 (3:108759264 C>CACTT)

Disease associations

OMIM: gene MIM:605645 | 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
GCST009391_1787	Metabolite levels	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004468	glucose measurement
EFO:0010477	fructose measurement
EFO:0010481	galactose measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cyclopamine	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
Decitabine	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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