MZB1

Summary

MZB1 (marginal zone B and B1 cell specific protein, HGNC:30125) is a protein-coding gene on chromosome 5q31.2, encoding Marginal zone B- and B1-cell-specific protein (Q8WU39). Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion.

Involved in positive regulation of cell population proliferation. Located in cytoplasm and extracellular region.

Source: NCBI Gene 51237 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 23 total — 1 pathogenic
• MANE Select transcript: NM_016459

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30125
Approved symbol	MZB1
Name	marginal zone B and B1 cell specific protein
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	PACAP, MGC29506, HSPC190, pERp1, MEDA-7
Ensembl gene	ENSG00000170476
Ensembl biotype	protein_coding
OMIM	609447
Entrez	51237

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding

ENST00000302125, ENST00000417694, ENST00000503120, ENST00000503351, ENST00000503481, ENST00000509591, ENST00000511979, ENST00000513389

RefSeq mRNA: 1 — MANE Select: NM_016459 NM_016459

CCDS: CCDS47273

Canonical transcript exons

ENST00000302125 — 4 exons

Exon	Start	End
ENSE00002030070	139389680	139389913
ENSE00003507348	139387467	139387921
ENSE00003654749	139388021	139388131
ENSE00003685632	139388461	139388585

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 97.85.

FANTOM5 (CAGE): breadth broad, TPM avg 9.3278 / max 867.4202, expressed in 214 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63747	5.3480	181
63746	3.5709	166
63745	0.3054	65
63741	0.0433	20
63742	0.0325	10
63744	0.0277	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.85	gold quality
spleen	UBERON:0002106	96.53	gold quality
lymph node	UBERON:0000029	96.30	gold quality
vermiform appendix	UBERON:0001154	95.23	gold quality
rectum	UBERON:0001052	94.49	gold quality
caecum	UBERON:0001153	94.45	gold quality
mucosa of transverse colon	UBERON:0004991	94.31	gold quality
tonsil	UBERON:0002372	94.02	gold quality
bone marrow cell	CL:0002092	93.59	gold quality
trachea	UBERON:0003126	92.98	gold quality
duodenum	UBERON:0002114	91.12	gold quality
colonic epithelium	UBERON:0000397	91.00	gold quality
parotid gland	UBERON:0001831	90.11	gold quality
bone marrow	UBERON:0002371	90.07	gold quality
pylorus	UBERON:0001166	89.16	gold quality
trabecular bone tissue	UBERON:0002483	88.47	gold quality
saliva-secreting gland	UBERON:0001044	87.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.04	gold quality
minor salivary gland	UBERON:0001830	86.41	gold quality
small intestine	UBERON:0002108	86.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.83	gold quality
epithelium of nasopharynx	UBERON:0001951	85.45	gold quality
nasopharynx	UBERON:0001728	85.44	gold quality
superficial temporal artery	UBERON:0001614	85.04	gold quality
granulocyte	CL:0000094	84.70	gold quality
tongue squamous epithelium	UBERON:0006919	84.63	gold quality
mouth mucosa	UBERON:0003729	84.25	gold quality
cardia of stomach	UBERON:0001162	83.98	gold quality
transverse colon	UBERON:0001157	83.93	gold quality
gall bladder	UBERON:0002110	82.71	gold quality

Single-cell (SCXA)

Detected in 45 experiment(s), a significant marker in 45.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	5997.40
E-MTAB-10432	yes	4736.24
E-HCAD-15	yes	4366.20
E-HCAD-32	yes	3974.17
E-HCAD-1	yes	3790.46
E-MTAB-6653	yes	3471.89
E-MTAB-8530	yes	3463.51
E-MTAB-8410	yes	3190.89
E-CURD-126	yes	3108.68
E-CURD-122	yes	3093.10
E-HCAD-9	yes	2768.02
E-CURD-46	yes	2575.16
E-CURD-55	yes	2538.19
E-CURD-77	yes	2474.45
E-MTAB-6308	yes	2472.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting MZB1, 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-4510	100.00	66.60	2050
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-6847-5P	97.93	66.74	1808

Literature-anchored findings (GeneRIF, showing 16)

• MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, was found to encode secreted-type protein with six conserved cysteine residues [MGC29506] (PMID:12792799)
• methylation-mediated silencing of MZB1 expression leads to loss of its tumor-suppressive activity, which may be a factor in hepatocarcinogenesis (PMID:22573353)
• Data show that proapoptotic caspase adapter protein PACAP is a potential serum marker of non-small cell lung cancer. (PMID:22613335)
• High expression of MZB1 predicts adverse prognosis in chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma and is associated with a unique gene expression signature. (PMID:23189934)
• results suggested that MGC29506 has the potential of functioning as a novel suppressor gene in gastric cancer (PMID:23434460)
• miR-185 regulates T cell development through its targeting of several mRNAs including Mzb1. (PMID:24014023)
• Low MZB1 expression was an independent prognostic factor for recurrence after curative gastrectomy and was associated significantly with increased hematogenous recurrence. MZB1 acts as a suppressor of GC. Low MZB1 expression in the primary GC tissue is predictive of recurrence after curative resection. (PMID:27459504)
• expression was positively correlated with a high accumulation of CD8(+) tumor-infiltrating lymphocytes in pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy (PMID:29180208)
• Data suggest that marginal zone B and B1 cell specific protein (MZB1) may be a potential therapeutic target in excessive antibody-secreting cells in systemic lupus erythematosus (SLE). (PMID:29382365)
• COL1A1 and MZB1 as the hub genes influenced the proliferation, invasion, migration and apoptosis of rectum adenocarcinoma cells by weighted correlation network analysis. (PMID:31901757)
• Proteomics and functional study reveal marginal zone B and B1 cell specific protein as a candidate marker of multiple myeloma. (PMID:32377723)
• High-resolution Crystal Structure of Human pERp1, A Saposin-like Protein Involved in IgA, IgM and Integrin Maturation in the Endoplasmic Reticulum. (PMID:33453188)
• MZB1 targeted by miR-185-5p inhibits the migration of human periodontal ligament cells through NF-kappaB signaling and promotes alveolar bone loss. (PMID:35653494)
• Altered expression of MZB1 in periodontitis: A possible link to disease pathogenesis. (PMID:37332260)
• MZB1-expressing cells are essential for local immunoglobulin production in chronic rhinosinusitis with nasal polyps. (PMID:37852603)
• MZB1 regulates cellular proliferation, mitochondrial dysfunction, and inflammation and targets the PI3K-Akt signaling pathway in acute pancreatitis. (PMID:38508349)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mzb1	ENSMUSG00000024353
rattus_norvegicus	Mzb1	ENSRNOG00000022009

Protein

Protein identifiers

Marginal zone B- and B1-cell-specific protein — Q8WU39 (reviewed: Q8WU39)

Alternative names: Mesenteric estrogen-dependent adipose 7, Plasma cell-induced resident endoplasmic reticulum protein, Proapoptotic caspase adapter protein

All UniProt accessions (3): Q8WU39, D6RII0, H0Y9L3

UniProt curated annotations — full annotation on UniProt →

Function. Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion. May exert its effect by acting as a molecular chaperone or as an oxidoreductase as it displays a low level of oxidoreductase activity. Isoform 2 may be involved in regulation of apoptosis. Helps to diversify peripheral B-cell functions by regulating Ca(2+) stores, antibody secretion and integrin activation. Acts as a hormone-regulated adipokine/pro-inflammatory cytokine that is implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes. May have a role in the onset of insulin resistance.

Subunit / interactions. Part of the ER chaperone complex, a multi-protein complex in the endoplasmic reticulum containing a large number of molecular chaperones which associates with unassembled incompletely folded immunoglobulin heavy chains. Isoform 2 interacts with CASP2 and CASP9. Interacts with HSP90B1 and PDIA3 in a calcium-dependent manner.

Subcellular location. Endoplasmic reticulum lumen. Secreted Cytoplasm.

Tissue specificity. Widely expressed with highest levels in adult brain, small intestine and lymphoid tissues such as thymus and spleen. Expression is frequently lower in intestinal-type gastric cancer. In obese patients, more abundant in omental than in subcutaneous fat.

Post-translational modifications. Forms an interchain disulfide bond with IgM monomers.

Induction. Down-regulated in primary B-cells early after ligand-stimulated activation. Up-regulated in bacterial lipopolysaccharides (LPS)-stimulated peritoneal macrophages.

Miscellaneous. Major.

Similarity. Belongs to the MZB1 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8WU39-1	1	yes
Q8WU39-2	2
Q8WU39-3	3
Q8WU39-4	4
Q8WU39-5	5

RefSeq proteins (1): NP_057543* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021852	DUF3456	Domain
IPR052682	MZB1	Family

Pfam: PF11938

UniProt features (28 total): splice variant 7, mutagenesis site 6, helix 6, strand 3, disulfide bond 3, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7AAH	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WU39-F1	84.90	0.59

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): 50–178, 53–171, 95–143

Mutagenesis-validated functional residues (6):

Position	Phenotype
50	does not affect activity.
53	no significant activity.
95	no significant activity.
143	no significant activity.
171	no significant activity.
178	does not affect activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 205 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_B_CELL_ACTIVATION, GOBP_B_CELL_PROLIFERATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION, GOBP_LEUKOCYTE_PROLIFERATION, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_INSULIN, GOBP_IMMUNOGLOBULIN_PRODUCTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION

GO Biological Process (7): positive regulation of immunoglobulin production (GO:0002639), apoptotic process (GO:0006915), positive regulation of cell population proliferation (GO:0008284), regulation of B cell proliferation (GO:0030888), integrin activation (GO:0033622), regulation of cell population proliferation (GO:0042127), regulation of insulin receptor signaling pathway (GO:0046626)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum chaperone complex (GO:0034663), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
cellular anatomical structure	2
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
B cell proliferation	1
regulation of lymphocyte proliferation	1
regulation of B cell activation	1
protein-containing complex assembly	1
regulation of cellular process	1
insulin receptor signaling pathway	1
regulation of signal transduction	1
binding	1
intracellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
endoplasmic reticulum protein-containing complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

903 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MZB1	CASP2	P42575	699
MZB1	MS4A1	P08984	668
MZB1	JCHAIN	P01591	643
MZB1	CD79A	P11912	618
MZB1	IGLL1	P15814	603
MZB1	MS4A2	Q01362	596
MZB1	CD3D	P04234	537
MZB1	NKG7	Q16617	493
MZB1	IGLL5	B9A064	493
MZB1	CASP9	P55211	493
MZB1	PDIA6	Q15084	486
MZB1	TNFRSF17	Q02223	478
MZB1	CALR	P27797	478
MZB1	PDIA3	P30101	476
MZB1	CANX	P27824	469

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MZB1	TSG101	psi-mi:“MI:0915”(physical association)	0.560
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
MZB1	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
ZNF747	TRIM28	psi-mi:“MI:0914”(association)	0.350
PIGH	ILVBL	psi-mi:“MI:0914”(association)	0.350
MZB1	KLHL22	psi-mi:“MI:0914”(association)	0.350
FUNDC2	SERPINA1	psi-mi:“MI:0914”(association)	0.350
TSG101	MZB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): MZB1 (Affinity Capture-MS), MZB1 (Two-hybrid), MZB1 (Affinity Capture-MS), MZB1 (Affinity Capture-MS), KLHL9 (Affinity Capture-MS), KLHL22 (Affinity Capture-MS), KLHL26 (Affinity Capture-MS), KLHL13 (Affinity Capture-MS), MZB1 (Affinity Capture-MS), MZB1 (Affinity Capture-MS), MZB1 (Protein-peptide), MZB1 (Affinity Capture-RNA), MZB1 (Two-hybrid)

ESM2 similar proteins: A0A5F4BST2, A0PJX4, A0RZB4, A1L515, A2A9Q0, A2BDG0, A6QQ85, A6XN32, A9JSM3, B0FP48, D3YZZ2, D4A2Q0, E5RIL1, F1SAM7, P01183, Q1RMK9, Q3UPR0, Q3ZCQ3, Q5BIV7, Q5BIV9, Q5BK01, Q5GH56, Q5GH64, Q5GH72, Q5SNT2, Q5T7M4, Q6IEE6, Q6PRD1, Q6UWJ8, Q70RD5, Q864V4, Q86UD0, Q8BWU1, Q8BX43, Q8CCB5, Q8IVY1, Q8K064, Q8K2Y3, Q8K5A9, Q8N9H8

Diamond homologs: A5PJ93, Q561R0, Q8WU39, Q9D8I1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	16
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
149858	GRCh38/hg38 5q23.3-33.2(chr5:129847794-153353546)x3	Pathogenic

SpliceAI

596 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139388459:A:AC	donor_gain	1.0000
5:139388459:ACT:A	donor_gain	1.0000
5:139388460:C:CC	donor_gain	1.0000
5:139388460:CT:C	donor_gain	1.0000
5:139388460:CTC:C	donor_gain	1.0000
5:139389675:CTCA:C	donor_loss	1.0000
5:139389676:TCACC:T	donor_loss	1.0000
5:139389677:CA:C	donor_loss	1.0000
5:139389678:A:AC	donor_gain	1.0000
5:139389679:C:CC	donor_gain	1.0000
5:139389679:C:CG	donor_loss	1.0000
5:139388140:A:T	acceptor_gain	0.9900
5:139388141:G:GC	acceptor_gain	0.9900
5:139388139:CAG:C	acceptor_gain	0.9800
5:139388141:G:C	acceptor_gain	0.9800
5:139388460:CTCCT:C	donor_gain	0.9800
5:139388465:G:A	donor_gain	0.9800
5:139389678:AC:A	donor_gain	0.9800
5:139389679:CC:C	donor_gain	0.9800
5:139389679:CCT:C	donor_gain	0.9800
5:139389679:CCTG:C	donor_gain	0.9800
5:139388132:C:CC	acceptor_gain	0.9700
5:139388455:ACT:A	donor_loss	0.9700
5:139388457:TCA:T	donor_loss	0.9700
5:139388458:CAC:C	donor_loss	0.9700
5:139388459:ACTC:A	donor_gain	0.9700
5:139388460:CTCC:C	donor_gain	0.9700
5:139388462:C:CA	donor_gain	0.9600
5:139388129:TAG:T	acceptor_gain	0.9500
5:139388461:T:A	donor_gain	0.9500

AlphaMissense

1193 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139388029:C:A	W135C	0.966
5:139388029:C:G	W135C	0.966
5:139388031:A:G	W135R	0.966
5:139388031:A:T	W135R	0.966
5:139388466:C:A	W99C	0.956
5:139388466:C:G	W99C	0.956
5:139389714:A:G	L48P	0.922
5:139387823:C:G	C171S	0.914
5:139387824:A:T	C171S	0.914
5:139388479:C:T	C95Y	0.914
5:139389693:G:T	A55D	0.914
5:139389703:C:G	A52P	0.914
5:139389699:C:T	C53Y	0.912
5:139388090:C:T	G115D	0.905
5:139388479:C:G	C95S	0.899
5:139388480:A:T	C95S	0.899
5:139388481:G:C	S94R	0.897
5:139388481:G:T	S94R	0.897
5:139388483:T:G	S94R	0.897
5:139387907:C:T	C143Y	0.896
5:139389708:C:G	C50S	0.895
5:139389709:A:T	C50S	0.895
5:139387921:C:A	R138S	0.893
5:139387921:C:G	R138S	0.893
5:139388468:A:G	W99R	0.892
5:139388468:A:T	W99R	0.892
5:139387908:A:G	C143R	0.891
5:139388123:A:T	V104D	0.888
5:139388478:G:C	C95W	0.885
5:139387906:A:C	C143W	0.883

dbSNP variants (sampled 300 via entrez): RS1000888807 (5:139387494 T>C), RS1001677169 (5:139388606 G>A,T), RS1002575849 (5:139391629 G>A), RS1002836123 (5:139388048 A>G), RS1004423034 (5:139391234 C>T), RS1005436119 (5:139389202 G>A,C), RS1005835662 (5:139389471 A>G), RS1006611689 (5:139388910 G>A), RS1007199692 (5:139389270 T>C), RS1008908026 (5:139387607 G>A,C), RS1009460406 (5:139387033 T>C), RS1011010441 (5:139390014 C>A,T), RS1011376827 (5:139390338 G>A,C), RS1011551587 (5:139390968 CCCCTCATCT>C), RS1012618425 (5:139390998 C>T)

Disease associations

OMIM: gene MIM:609447 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005951_151	Body mass index	6.000000e-07
GCST010725_68	Malaria	4.000000e-07
GCST010725_7	Malaria	2.000000e-06
GCST010796_3063	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3064	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_3065	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-14
GCST010796_3066	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
fluorene-9-bisphenol	decreases expression	1
bisphenol A	decreases methylation	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	decreases expression	1
Demecolcine	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Vincristine	decreases expression	1
Zinc	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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