FCRLB

Summary

FCRLB (Fc receptor like B, HGNC:26431) is a protein-coding gene on chromosome 1q23.3, encoding Fc receptor-like B (Q6BAA4).

FCRL2 belongs to the Fc receptor family. Fc receptors are involved in phagocytosis, antibody-dependent cell cytotoxicity, immediate hypersensitivity, and transcytosis of immunoglobulins via their ability to bind immunoglobulin (Ig) constant regions (Chikaev et al., 2005 [PubMed 15676285]).

Source: NCBI Gene 127943 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_001002901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26431
Approved symbol	FCRLB
Name	Fc receptor like B
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31052, FCRL2, FREB-2, FCRLY
Ensembl gene	ENSG00000162746
Ensembl biotype	protein_coding
OMIM	609251
Entrez	127943

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000336830, ENST00000367944, ENST00000367945, ENST00000367946, ENST00000367948, ENST00000495397

RefSeq mRNA: 6 — MANE Select: NM_001002901 NM_001002901, NM_001288829, NM_001288830, NM_001288831, NM_001288832, NM_001320241

CCDS: CCDS30927, CCDS72962, CCDS72963, CCDS72964, CCDS72965

Canonical transcript exons

ENST00000367948 — 8 exons

Exon	Start	End
ENSE00001299005	161726703	161726993
ENSE00001353896	161725821	161726087
ENSE00001408135	161723367	161723621
ENSE00001416357	161722989	161723009
ENSE00001445986	161722653	161722703
ENSE00001445987	161721755	161721850
ENSE00001510911	161727247	161728143
ENSE00003978208	161721544	161721661

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 86.73.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5659 / max 63.2656, expressed in 185 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6276	0.3880	152
6277	0.1749	46
6275	0.0030	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	86.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.58	gold quality
left ventricle myocardium	UBERON:0006566	85.87	gold quality
kidney epithelium	UBERON:0004819	78.79	gold quality
granulocyte	CL:0000094	74.20	gold quality
middle temporal gyrus	UBERON:0002771	73.19	silver quality
Brodmann (1909) area 23	UBERON:0013554	72.10	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.90	silver quality
seminal vesicle	UBERON:0000998	69.69	gold quality
myocardium	UBERON:0002349	68.24	gold quality
adult mammalian kidney	UBERON:0000082	66.72	gold quality
primary visual cortex	UBERON:0002436	66.67	gold quality
metanephros	UBERON:0000081	65.65	gold quality
prefrontal cortex	UBERON:0000451	65.57	gold quality
parotid gland	UBERON:0001831	65.52	silver quality
stromal cell of endometrium	CL:0002255	65.06	gold quality
kidney	UBERON:0002113	64.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.42	gold quality
germinal epithelium of ovary	UBERON:0001304	64.37	gold quality
vermiform appendix	UBERON:0001154	64.30	gold quality
frontal cortex	UBERON:0001870	63.90	gold quality
neocortex	UBERON:0001950	63.52	gold quality
superior frontal gyrus	UBERON:0002661	63.26	gold quality
spleen	UBERON:0002106	63.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.20	gold quality
anterior cingulate cortex	UBERON:0009835	63.16	gold quality
right frontal lobe	UBERON:0002810	63.03	gold quality
tibial nerve	UBERON:0001323	62.97	gold quality
cerebral cortex	UBERON:0000956	62.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.48

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Expression analysis revealed FCRL2 mRNA only in placenta.FCRL2 is differentially expressed by transformed B cell lines. (PMID:15676285)
• Fcry is upregulated by short-term treatment with BAFF/BLyS, which promotes B cell survival rather than proliferation (PMID:16263223)
• The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgA nephropathy in a large Chinese cohort. (PMID:23593433)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fcrlb	ENSMUSG00000070524
rattus_norvegicus	Fcrlb	ENSRNOG00000003135

Paralogs (17): FCGR2B (ENSG00000072694), FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), FCRL3 (ENSG00000160856), FCGR3B (ENSG00000162747), FCRL4 (ENSG00000163518), FCRL1 (ENSG00000163534), FCER1A (ENSG00000179639), FCRL6 (ENSG00000181036), C17orf99 (ENSG00000187997), FCGR3A (ENSG00000203747), FCGR2C (ENSG00000244682), PECAM1 (ENSG00000261371), MILR1 (ENSG00000271605)

Protein

Protein identifiers

Fc receptor-like B — Q6BAA4 (reviewed: Q6BAA4)

Alternative names: Fc receptor homolog expressed in B-cells protein 2, Fc receptor-like and mucin-like protein 2, Fc receptor-like protein 2, Fc receptor-related protein Y

All UniProt accessions (1): Q6BAA4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Endoplasmic reticulum.

Tissue specificity. Expressed at low levels. Expressed in B-lymphocytes. Detected in tonsil, lung, kidney, spleen and placenta. Expressed by a small subset of germinal center B-cells in tonsils and by melanocytes (at protein level).

Isoforms (5)

UniProt ID	Names	Canonical?
Q6BAA4-1	1	yes
Q6BAA4-2	2, FCRL2c1
Q6BAA4-3	3, FCRL2c2
Q6BAA4-4	4, FCRL2b1
Q6BAA4-5	5, FCRL2b2

RefSeq proteins (6): NP_001002901, NP_001275758, NP_001275759, NP_001275760, NP_001275761, NP_001307170 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050488	Ig_Fc_receptor	Family

Pfam: PF13895

UniProt features (15 total): splice variant 5, domain 2, disulfide bond 2, signal peptide 1, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6BAA4-F1	76.03	0.50

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 (2): 44–85, 124–168

Glycosylation sites (1): 152

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GCANCTGNY_MYOD_Q6, GOCC_CELL_SURFACE, CAGCTG_AP4_Q5, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_CELL_CELL_SIGNALING, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, MODULE_301, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_IMMUNE_EFFECTOR_PROCESS, BILBAN_B_CLL_LPL_DN, MODULE_188

GO Biological Process (3): cell surface receptor signaling pathway (GO:0007166), immunoglobulin mediated immune response (GO:0016064), negative regulation of immune response (GO:0050777)

GO Molecular Function (1): transmembrane signaling receptor activity (GO:0004888)

GO Cellular Component (3): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), external side of plasma membrane (GO:0009897)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	1
B cell mediated immunity	1
negative regulation of immune system process	1
immune response	1
negative regulation of response to stimulus	1
regulation of immune response	1
signaling receptor activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCRLB	FCER1G	P30273	528
FCRLB	FCGRT	P55899	446
FCRLB	PLA2R1	Q13018	378
FCRLB	MRC2	Q9UBG0	327
FCRLB	ZBTB1	Q9Y2K1	290
FCRLB	CLEC4E	Q9ULY5	277
FCRLB	VSTM4	Q8IW00	270
FCRLB	CLEC6A	Q6EIG7	270
FCRLB	FCRL1	Q96LA6	269
FCRLB	LY9	Q9HBG7	265
FCRLB	DNAJB5	O75953	259
FCRLB	TYROBP	O43914	250
FCRLB	METTL23	Q86XA0	248
FCRLB	CARD9	Q9H257	248
FCRLB	IGSF9	Q9P2J2	246
FCRLB	IGSF9B	Q9UPX0	246

IntAct

0 interactions, top by confidence:

BioGRID (2): FCRLB (Positive Genetic), FCRLB (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A0A0B4J1G0, A3RFZ7, E2RP87, G1T7E7, G1TR84, H0VDZ8, M3XWH1, O75015, P08101, P08508, P08637, P0DTI4, P12314, P12318, P12319, P12371, P20489, P26151, P27645, P31994, P31995, P79107, Q09TM2, Q09TM4, Q28110, Q28942, Q3B8P2, Q5DRQ8, Q60513, Q63203, Q6BAA4, Q6XPU4, Q8SPV8, Q8SPW2, Q920A9, Q92637, Q96PJ5, Q96RD9, Q9N2I5, Q68SN8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2699 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161723567:T:A	C85S	0.999
1:161723568:G:C	C85S	0.999
1:161723497:G:C	W61C	0.998
1:161723497:G:T	W61C	0.998
1:161723561:T:G	Y83D	0.998
1:161723567:T:C	C85R	0.998
1:161723591:A:C	S93R	0.998
1:161723593:T:A	S93R	0.998
1:161723593:T:G	S93R	0.998
1:161725883:T:A	C124S	0.998
1:161725883:T:C	C124R	0.998
1:161725884:G:C	C124S	0.998
1:161726015:T:A	C168S	0.998
1:161726016:G:C	C168S	0.998
1:161723444:T:A	C44S	0.997
1:161723445:G:C	C44S	0.997
1:161723495:T:A	W61R	0.997
1:161723495:T:C	W61R	0.997
1:161725884:G:A	C124Y	0.997
1:161725885:C:G	C124W	0.997
1:161726015:T:C	C168R	0.997
1:161726017:C:G	C168W	0.997
1:161723407:G:C	W31C	0.996
1:161723407:G:T	W31C	0.996
1:161723569:C:G	C85W	0.996
1:161723592:G:T	S93I	0.996
1:161725825:G:C	W104C	0.996
1:161725825:G:T	W104C	0.996
1:161726009:T:G	Y166D	0.996
1:161726783:T:A	C219S	0.996

dbSNP variants (sampled 300 via entrez): RS1000292347 (1:161727799 G>C), RS1000600589 (1:161726144 A>G), RS1001056069 (1:161726511 C>G,T), RS1001151862 (1:161724570 T>C), RS1001245698 (1:161721833 G>A), RS1001483632 (1:161727479 C>T), RS1001618313 (1:161719726 T>C), RS1001668794 (1:161720022 T>C), RS1001831276 (1:161727271 C>A,G), RS1002217007 (1:161720222 C>T), RS1002324468 (1:161724930 C>G), RS1002636088 (1:161724663 C>T), RS1004103135 (1:161719912 G>A), RS1004232521 (1:161721786 G>A), RS1004473639 (1:161728202 A>C,G)

Disease associations

OMIM: gene MIM:609251 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005973_20	White blood cell count	2.000000e-08
GCST005987_23	Albumin-globulin ratio	6.000000e-15
GCST005990_39	Non-albumin protein levels	4.000000e-21
GCST008478_3	Neurological blood protein biomarker levels	4.000000e-21
GCST012181_1	smoking initiation in schizophrenia	7.000000e-07
GCST90011900_53	Serum alkaline phosphatase levels	3.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005128	albumin:globulin ratio measurement
EFO:0005670	smoking initiation
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, decreases expression, affects methylation, affects cotreatment	2
Estradiol	affects expression, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Ethyl Methanesulfonate	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Niclosamide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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