JCHAIN

Summary

JCHAIN (joining chain of multimeric IgA and IgM, HGNC:5713) is a protein-coding gene on chromosome 4q13.3, encoding Immunoglobulin J chain (P01591). Serves to link two monomer units of either IgM or IgA.

Enables IgA binding activity and protein homodimerization activity. Contributes to several functions, including immunoglobulin receptor binding activity; peptidoglycan binding activity; and phosphatidylcholine binding activity. Involved in several processes, including glomerular filtration; innate immune response; and positive regulation of respiratory burst. Located in extracellular space. Part of monomeric IgA immunoglobulin complex; pentameric IgM immunoglobulin complex; and secretory dimeric IgA immunoglobulin complex.

Source: NCBI Gene 3512 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_144646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5713
Approved symbol	JCHAIN
Name	joining chain of multimeric IgA and IgM
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	IGCJ, JCH
Ensembl gene	ENSG00000132465
Ensembl biotype	protein_coding
OMIM	147790
Entrez	3512

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000254801, ENST00000391614, ENST00000470866, ENST00000510437, ENST00000510614, ENST00000856250, ENST00000944536

RefSeq mRNA: 1 — MANE Select: NM_144646 NM_144646

CCDS: CCDS3545

Canonical transcript exons

ENST00000254801 — 4 exons

Exon	Start	End
ENSE00000720299	70657211	70657291
ENSE00001138846	70662092	70662215
ENSE00001170989	70666427	70666508
ENSE00001296649	70655541	70656539

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.96.

FANTOM5 (CAGE): breadth broad, TPM avg 42.9391 / max 4245.1626, expressed in 381 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52430	31.7334	204
52431	7.7551	179
52432	2.4983	229
203210	0.4426	80
52433	0.2678	50
52434	0.2420	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	99.96	gold quality
jejunal mucosa	UBERON:0000399	99.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.89	gold quality
pylorus	UBERON:0001166	99.83	gold quality
caecum	UBERON:0001153	99.77	gold quality
mucosa of transverse colon	UBERON:0004991	99.75	gold quality
vermiform appendix	UBERON:0001154	99.73	gold quality
colonic mucosa	UBERON:0000317	99.63	gold quality
epithelium of nasopharynx	UBERON:0001951	99.62	gold quality
nasopharynx	UBERON:0001728	99.61	gold quality
duodenum	UBERON:0002114	99.58	gold quality
trachea	UBERON:0003126	99.34	gold quality
tonsil	UBERON:0002372	99.28	gold quality
cardia of stomach	UBERON:0001162	99.27	gold quality
parotid gland	UBERON:0001831	99.19	gold quality
spleen	UBERON:0002106	99.07	gold quality
colonic epithelium	UBERON:0000397	99.02	gold quality
trabecular bone tissue	UBERON:0002483	98.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.88	gold quality
mammary duct	UBERON:0001765	98.81	gold quality
gall bladder	UBERON:0002110	98.78	gold quality
bone marrow cell	CL:0002092	98.60	gold quality
lower lobe of lung	UBERON:0008949	98.18	gold quality
epithelium of mammary gland	UBERON:0003244	98.16	gold quality
ileal mucosa	UBERON:0000331	98.08	gold quality
lymph node	UBERON:0000029	97.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.59	gold quality
monocyte	CL:0000576	97.33	gold quality
mononuclear cell	CL:0000842	97.28	gold quality
adult organism	UBERON:0007023	97.04	gold quality

Single-cell (SCXA)

Detected in 54 experiment(s), a significant marker in 53.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	109570.68
E-CURD-89	yes	97280.35
E-CURD-88	yes	94401.51
E-MTAB-8410	yes	87773.90
E-HCAD-11	yes	77311.24
E-GEOD-125970	yes	51047.45
E-CURD-122	yes	40971.21
E-MTAB-8322	yes	31973.86
E-MTAB-9543	yes	30078.96
E-MTAB-6386	yes	29479.17
E-MTAB-6653	yes	29176.77
E-HCAD-1	yes	26948.02
E-MTAB-8142	yes	26221.73
E-HCAD-15	yes	20767.53
E-MTAB-8207	yes	19534.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, MEF2C, PAX5, SPI1, TCF3, USF1

miRNA regulators (miRDB)

54 targeting JCHAIN, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-6737-3P	98.95	68.56	1577

Literature-anchored findings (GeneRIF, showing 3)

• TLR2 ligands induce CCR9 and CCR10 expression by circulating B-cells and increase their chemotaxis. TLR2 stimulation also induced J chain and IgA production demonstrating the induction of mucosal-like antibody secreting cells. (PMID:20947433)
• Results show that ID1, ID3 and IGJ genes are highly expressed in adult B-ALL and correlate with poor prognosis in Hispanic patients. (PMID:27044543)
• IGJ suppresses breast cancer growth and metastasis by inhibiting EMT via the NF-kappaB signaling pathway. (PMID:37539706)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Jchain	ENSMUSG00000067149
rattus_norvegicus	Jchain	ENSRNOG00000003666

Protein

Protein identifiers

Immunoglobulin J chain — P01591 (reviewed: P01591)

Alternative names: Joining chain of multimeric IgA and IgM

All UniProt accessions (4): P01591, C9JA05, D6RD17, D6RHJ6

UniProt curated annotations — full annotation on UniProt →

Function. Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces dimers and/or larger polymers. It also helps to bind these immunoglobulins to secretory component.

Subunit / interactions. Part of the secretory IgA (sIgA) complex that consists of two, four or five IgA monomers, and two additional non-Ig polypeptides, namely the JCHAIN and the secretory component (the proteolytic product of PIGR). Part of the secretory IgM (sIgM) complex that consists of five IgM monomers, and two additional non-Ig polypeptides, namely the JCHAIN and the secretory component (the proteolytic product of PIGR). JCHAIN-containing IgM interacts (via CH4 domain) with FCRM (via Ig-like domain).

Subcellular location. Secreted.

RefSeq proteins (1): NP_653247* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024110	Ig_J	Family

Pfam: PF15097

UniProt features (25 total): strand 13, disulfide bond 5, turn 2, signal peptide 1, chain 1, helix 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
6UE7	ELECTRON MICROSCOPY	2.9
6UE9	ELECTRON MICROSCOPY	2.9
6UE8	ELECTRON MICROSCOPY	3
6UEA	ELECTRON MICROSCOPY	3
8SKV	ELECTRON MICROSCOPY	3.1
6LX3	ELECTRON MICROSCOPY	3.15
7YSG	ELECTRON MICROSCOPY	3.18
8SKU	ELECTRON MICROSCOPY	3.2
6LXW	ELECTRON MICROSCOPY	3.27
7K0C	ELECTRON MICROSCOPY	3.3
7YG2	ELECTRON MICROSCOPY	3.32
7YTC	ELECTRON MICROSCOPY	3.39
8WYR	ELECTRON MICROSCOPY	3.39
6KXS	ELECTRON MICROSCOPY	3.4
8WYS	ELECTRON MICROSCOPY	3.41
8BPF	ELECTRON MICROSCOPY	3.5
7Y0H	ELECTRON MICROSCOPY	3.56
8R83	ELECTRON MICROSCOPY	3.57
8GZN	ELECTRON MICROSCOPY	3.6
8R84	ELECTRON MICROSCOPY	3.6
9ARV	ELECTRON MICROSCOPY	3.6
7Y0J	ELECTRON MICROSCOPY	3.62
8BPE	ELECTRON MICROSCOPY	3.63
7Y09	ELECTRON MICROSCOPY	3.71
7YTD	ELECTRON MICROSCOPY	3.71
8ADY	ELECTRON MICROSCOPY	5.2
8ADZ	ELECTRON MICROSCOPY	6.7
8AE3	ELECTRON MICROSCOPY	6.8
8AE0	ELECTRON MICROSCOPY	7.1
8AE2	ELECTRON MICROSCOPY	8.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01591-F1	87.13	0.60

Antibody-complex structures (SAbDab): 5 — 8ADY, 8ADZ, 8AE0, 8AE2, 8AE3

Functional residue map

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

Post-translational modifications (1): 23

Disulfide bonds (5): 35–123, 37, 91, 94–114, 131–156

Glycosylation sites (1): 71

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-2168880	Scavenging of heme from plasma

MSigDB gene sets: 269 (showing top): GOBP_REGULATION_OF_RESPIRATORY_BURST, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, MODULE_45, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, CROONQUIST_NRAS_SIGNALING_UP, MEF2_02, GOLDRATH_ANTIGEN_RESPONSE, chr4q13, HAHTOLA_MYCOSIS_FUNGOIDES_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_3, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GRAHAM_CML_QUIESCENT_VS_NORMAL_DIVIDING_DN

GO Biological Process (8): adaptive immune response (GO:0002250), glomerular filtration (GO:0003094), immune response (GO:0006955), humoral immune response (GO:0006959), antibacterial humoral response (GO:0019731), innate immune response (GO:0045087), positive regulation of respiratory burst (GO:0060267), protein-containing complex assembly (GO:0065003)

GO Molecular Function (8): antigen binding (GO:0003823), IgA binding (GO:0019862), protein-macromolecule adaptor activity (GO:0030674), immunoglobulin receptor binding (GO:0034987), protein homodimerization activity (GO:0042803), single-stranded DNA binding (GO:0003697), phosphatidylcholine binding (GO:0031210), peptidoglycan binding (GO:0042834)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), monomeric IgA immunoglobulin complex (GO:0071748), dimeric IgA immunoglobulin complex (GO:0071750), secretory IgA immunoglobulin complex (GO:0071751), secretory dimeric IgA immunoglobulin complex (GO:0071752), pentameric IgM immunoglobulin complex (GO:0071756), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Binding and Uptake of Ligands by Scavenger Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	3
cellular anatomical structure	2
polymeric IgA immunoglobulin complex	2
renal filtration	1
immune system process	1
response to stimulus	1
antimicrobial humoral response	1
defense response to bacterium	1
defense response to symbiont	1
positive regulation of metabolic process	1
respiratory burst	1
regulation of respiratory burst	1
cellular component assembly	1
protein-containing complex organization	1
binding	1
immunoglobulin binding	1
protein binding	1
molecular adaptor activity	1
signaling receptor binding	1
identical protein binding	1
protein dimerization activity	1
DNA binding	1
phospholipid binding	1
cation binding	1
quaternary ammonium group binding	1
glycosaminoglycan binding	1
extracellular vesicle	1
IgA immunoglobulin complex, circulating	1
dimeric IgA immunoglobulin complex	1
secretory IgA immunoglobulin complex	1
IgM immunoglobulin complex, circulating	1
extracellular region	1

Protein interactions and networks

STRING

1822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JCHAIN	PIGR	P01833	999
JCHAIN	UTP3	Q9NQZ2	923
JCHAIN	ERP44	Q9BS26	870
JCHAIN	ERO1B	Q86YB8	833
JCHAIN	LAP3	P28838	766
JCHAIN	PIGA	P37287	760
JCHAIN	FCAR	P24071	715
JCHAIN	IGLL5	B9A064	699
JCHAIN	ERO1A	Q96HE7	661
JCHAIN	IGLL1	P15814	647
JCHAIN	PGM2	Q96G03	647
JCHAIN	MZB1	Q8WU39	643
JCHAIN	IGHV4-38-2	P0DP08	588
JCHAIN	CD79A	P11912	575
JCHAIN	CBFB	Q13951	549

IntAct

96 interactions, top by confidence:

A	B	Type	Score
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
ARMCX3	RANBP6	psi-mi:“MI:0914”(association)	0.730
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
ICE2	HP	psi-mi:“MI:0914”(association)	0.530
RHOBTB1	CST4	psi-mi:“MI:0914”(association)	0.530
GTF2B	CST4	psi-mi:“MI:0914”(association)	0.530
PLEKHG6	CST4	psi-mi:“MI:0914”(association)	0.530
ZNF491	CST4	psi-mi:“MI:0914”(association)	0.530
TRIAP1	JCHAIN	psi-mi:“MI:0914”(association)	0.530
APCDD1	JCHAIN	psi-mi:“MI:0914”(association)	0.530
SLC25A15	JCHAIN	psi-mi:“MI:0914”(association)	0.530
TMEM237	CLGN	psi-mi:“MI:0914”(association)	0.530
KIR2DS2	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
NPB	CST4	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
	LECT2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (87): IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGJ (Affinity Capture-MS)

ESM2 similar proteins: A0A385DTH1, A0A7H0DN76, A4ZUA0, A6LT23, C3KVX7, C4LBG4, D4H539, J7T0S1, O10620, O34838, P01591, P07970, P07971, P0C6F5, P0C6F8, P0C6T4, P0C6T7, P0C6V9, P0C6W2, P0C6W3, P0C6W6, P0CA95, P0CAB9, P0DTC1, P0DTD1, P0DUB2, P17003, P17004, P17005, P23108, P29815, P52471, P87691, Q04916, Q45UF8, Q5UNX6, Q5UPF9, Q5UPS4, Q5UQG1, Q5UQT5

Diamond homologs: P01591, P01592, P0DUB2, P23108

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

545 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70656535:TACAG:T	acceptor_gain	1.0000
4:70656536:ACAG:A	acceptor_gain	1.0000
4:70656537:CAG:C	acceptor_gain	1.0000
4:70656537:CAGC:C	acceptor_gain	1.0000
4:70656538:AG:A	acceptor_gain	1.0000
4:70656538:AGC:A	acceptor_loss	1.0000
4:70656539:GCT:G	acceptor_loss	1.0000
4:70656540:C:CC	acceptor_gain	1.0000
4:70657209:A:AC	donor_gain	1.0000
4:70657210:C:CC	donor_gain	1.0000
4:70657210:CAGGT:C	donor_gain	1.0000
4:70657234:T:C	donor_gain	1.0000
4:70657287:GAACA:G	acceptor_gain	1.0000
4:70657289:ACA:A	acceptor_gain	1.0000
4:70657289:ACAC:A	acceptor_loss	1.0000
4:70657290:CA:C	acceptor_gain	1.0000
4:70657290:CAC:C	acceptor_gain	1.0000
4:70657290:CACTA:C	acceptor_loss	1.0000
4:70657291:AC:A	acceptor_loss	1.0000
4:70657292:C:CA	acceptor_loss	1.0000
4:70657292:C:CC	acceptor_gain	1.0000
4:70657293:T:C	acceptor_loss	1.0000
4:70662088:ATAC:A	donor_loss	1.0000
4:70662089:TA:T	donor_loss	1.0000
4:70662090:A:AC	donor_gain	1.0000
4:70662090:A:AG	donor_loss	1.0000
4:70662091:C:CC	donor_gain	1.0000
4:70662091:CAT:C	donor_gain	1.0000
4:70662091:CATA:C	donor_gain	1.0000
4:70662091:CATAA:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000552678 (4:70660106 C>G), RS1000618997 (4:70664161 A>C,G,T), RS1000694371 (4:70664006 A>C,G), RS1000882902 (4:70664792 T>C), RS1001092244 (4:70659298 C>A), RS1001283766 (4:70667238 A>G), RS1001461295 (4:70659604 G>A,C), RS1001563774 (4:70660435 C>T), RS1001722862 (4:70661102 A>G), RS1001961911 (4:70655568 A>G), RS1002057035 (4:70660176 A>G), RS1002279351 (4:70659224 T>A), RS1002417138 (4:70664390 G>A), RS1002689937 (4:70665414 C>A,T), RS1002721432 (4:70663612 G>A)

Disease associations

OMIM: gene MIM:147790 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	affects binding, decreases expression, increases expression	3
Zinc	affects binding, increases expression	2
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
arsenite	decreases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases methylation	1
tetrathiomolybdate	increases expression	1
caprylic aldehyde	increases methylation	1
hydroquinone	decreases expression	1
pentanal	increases methylation	1
heptanal	increases methylation	1
CGP 52608	affects binding, increases reaction	1
incobotulinumtoxinA	increases expression	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Cadmium	affects binding	1
Demecolcine	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydroxychloroquine	affects cotreatment, decreases expression	1
Lead	affects binding	1
Methotrexate	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Pesticides	increases expression	1
Sulfasalazine	affects cotreatment, decreases expression	1
Dronabinol	decreases expression	1

Clinical trials (associated diseases)

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