JCHAIN

Chr 4

joining chain of multimeric IgA and IgM

Also known as: IGCJ, IGJ, JCH

NCBI Gene: 3512 ENSG00000132465 UniProt: P01591 OMIM: 147790

The J chain protein links IgM and IgA immunoglobulin monomers to form pentameric IgM complexes and dimeric/polymeric IgA complexes, and facilitates binding to secretory component for mucosal immunity. Mutations cause immunodeficiency with absent serum IgM and decreased secretory IgA, resulting in recurrent infections particularly affecting respiratory and gastrointestinal tracts. This follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.24

Clinical Summary— JCHAIN

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 VUS of 18 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.034

Z-score 1.19

OE 0.48 (0.22–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.14Z-score

OE missense 0.96 (0.80–1.15)

84 obs / 87.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.22–1.24)

0≤0.351.4

Missense OE?0.96 (0.80–1.15)

0≤0.61.4

Synonymous OE?0.73

0≤1.21.6

LoF obs/exp: 3 / 6.2Missense obs/exp: 84 / 87.7Syn Z: 1.21

This gene — mechanism propensity

0.5181th %ile

GOF

0.6345th %ile

LOF

0.2775th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

18 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	13	0	13
Likely Benign	1	2	3
Benign	0	0	0
Total	14	2	16

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap JCHAIN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →