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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FCRL4
Fc receptor like 4
Chromosome 1 · 1q23.1
NCBI Gene: 83417Ensembl: ENSG00000163518.11HGNC: HGNC:18507UniProt: Q96PJ5
43PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcell surfacecell surface receptor signaling pathwayexternal side of plasma membranehemangioblastomacutaneous melanomaskin squamous cell carcinomacarcinoma of liver and intrahepatic biliary tract
✦AI Summary

FCRL4 (Fc receptor like 4) is an immunoregulatory receptor primarily expressed on memory B cells that functions as an inhibitor of B-cell receptor signaling. FCRL4 serves as a bona fide Fc receptor, binding efficiently to IgA antibodies and functioning in immune complex-dependent B cell regulation 1. The receptor is specifically expressed by memory B cells localized in sub-epithelial regions of lymphoid tissues in healthy individuals 2. FCRL4+ B cells represent a distinct memory B cell subset defined by phenotypic markers and display functional heterogeneity, including reduced proliferation and differentiation potential compared to FCRL4- cells 32. These cells strongly express inhibitory receptor genes and demonstrate two-fold lower cell division rates, making them less prone to differentiate into plasma cells 2. Pathologically, FCRL4+ B cells are expanded in various infectious and autoimmune disorders, including Sjögren's syndrome where tissue-resident FCRL4+ B cells produce enhanced pro-inflammatory cytokines and serve as key drivers in patients with MALT-lymphomas 4. In nasopharyngeal carcinoma, CD20+FCRL4+ B cells interact with CD8+ T cells through the MHC-I pathway and correlate positively with PD-1 expression and anti-PD-1 therapy response 5. Decreased FCRL4 expression has been associated with rheumatoid arthritis, suggesting its contribution to inflammatory processes 6.

Sources cited
1
FCRL4 is a bona fide Fc receptor that binds efficiently to IgA
PMID: 22491254
2
FCRL4 is expressed by memory B cells in sub-epithelial regions and generated cells show reduced proliferation
PMID: 28636654
3
FCRL4+ B cells represent a distinct memory B cell subset with functional heterogeneity
PMID: 34396546
4
FCRL4+ B cells are expanded in autoimmune disorders and produce pro-inflammatory cytokines in Sjögren's syndrome
PMID: 34168653
5
CD20+FCRL4+ B cells interact with CD8+ T cells and correlate with anti-PD-1 therapy response
PMID: 41504259
6
Decreased FCRL4 expression is associated with rheumatoid arthritis
PMID: 27193470
Disease Associationsⓘ20
breast ductal adenocarcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
hemangioblastomaOpen Targets
0.37Weak
lung carcinomaOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
squamous cell lung carcinomaOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
IGA glomerulonephritisOpen Targets
0.35Weak
functional neutrophil defectOpen Targets
0.32Weak
lung adenocarcinomaOpen Targets
0.29Weak
non-small cell lung carcinomaOpen Targets
0.29Weak
breast carcinomaOpen Targets
0.28Weak
gastric carcinomaOpen Targets
0.28Weak
esophageal squamous cell carcinomaOpen Targets
0.28Weak
head and neck squamous cell carcinomaOpen Targets
0.28Weak
oral squamous cell carcinomaOpen Targets
0.28Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MS4A2Shared pathway100%IGSF6Shared pathway100%C17orf99Shared pathway100%FCRL6Shared pathway100%FCRLAShared pathway100%PIGRProtein interaction80%
Tissue Expression6 tissues
Brain
100%
Ovary
0%
Liver
0%
Heart
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
FCRL4MS4A2IGSF6C17orf99FCRL6FCRLAPIGR
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96PJ5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.82LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.63 [0.49–0.82]
RankingsWhere FCRL4 stands among ~20K protein-coding genes
  • #9,726of 20,598
    Most Researched43
  • #6,964of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedFCRL4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing.
PMID: 36869384
Genome Med · 2023
1.00
2
Memory B cells and plasma cells: The differentiative continuum of humoral immunity.
PMID: 34396546
Immunol Rev · 2021
0.90
3
The Multiple Roles of B Cells in the Pathogenesis of Sjögren's Syndrome.
PMID: 34168653
Front Immunol · 2021
0.80
4
Cutting edge: human FcRL4 and FcRL5 are receptors for IgA and IgG.
PMID: 22491254
J Immunol · 2012
0.70
5
Case-only designs for exploring the interaction between FCRL4 gene and suspected environmental factors in patients with ankylosing spondylitis.
PMID: 25012527
Inflammation · 2015
0.60