FCRLA

Summary

FCRLA (Fc receptor like A, HGNC:18504) is a protein-coding gene on chromosome 1q23.3, encoding Fc receptor-like A (Q7L513). May be implicated in B-cell differentiation and lymphomagenesis.

This gene encodes a protein similar to receptors for the Fc fragment of gamma immunoglobulin (IgG). These receptors, referred to as FCGRs, mediate the destruction of IgG-coated antigens and of cells induced by antibodies. This encoded protein is selectively expressed in B cells, and may be involved in their development. This protein may also be involved in the development of lymphomas. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 84824 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_032738

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18504
Approved symbol	FCRLA
Name	Fc receptor like A
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC4595, FCRLc2, FCRLb, FCRLc1, FCRLd, FCRLe, FCRL, FREB, FCRLX
Ensembl gene	ENSG00000132185
Ensembl biotype	protein_coding
OMIM	606891
Entrez	84824

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000236938, ENST00000294796, ENST00000309691, ENST00000349527, ENST00000350710, ENST00000367949, ENST00000367950, ENST00000367953, ENST00000367957, ENST00000367959, ENST00000465403, ENST00000470841, ENST00000540521, ENST00000546024, ENST00000674251, ENST00000674323, ENST00000954393

RefSeq mRNA: 9 — MANE Select: NM_032738 NM_001184866, NM_001184867, NM_001184870, NM_001184871, NM_001184872, NM_001184873, NM_001366195, NM_001366196, NM_032738

CCDS: CCDS30926, CCDS53415, CCDS53416, CCDS53417, CCDS53419, CCDS91091

Canonical transcript exons

ENST00000236938 — 5 exons

Exon	Start	End
ENSE00000796511	161711208	161711474
ENSE00000899905	161710760	161710912
ENSE00000899907	161711934	161712218
ENSE00003899959	161707229	161707343
ENSE00003902514	161713085	161714352

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 93.26.

FANTOM5 (CAGE): breadth broad, TPM avg 5.4157 / max 521.5938, expressed in 438 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6272	3.6487	179
6274	0.5721	70
6268	0.4694	219
6270	0.3051	80
6273	0.1905	48
6269	0.1350	40
201789	0.0645	27
6271	0.0304	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	93.26	gold quality
lymph node	UBERON:0000029	92.69	gold quality
epithelium of nasopharynx	UBERON:0001951	92.07	gold quality
nasopharynx	UBERON:0001728	92.05	gold quality
spleen	UBERON:0002106	90.58	gold quality
vermiform appendix	UBERON:0001154	88.81	gold quality
superficial temporal artery	UBERON:0001614	88.76	gold quality
pancreatic ductal cell	CL:0002079	86.51	silver quality
bone marrow cell	CL:0002092	85.16	gold quality
granulocyte	CL:0000094	83.40	gold quality
caecum	UBERON:0001153	82.11	gold quality
blood	UBERON:0000178	80.38	gold quality
bone marrow	UBERON:0002371	80.01	gold quality
tonsil	UBERON:0002372	79.79	gold quality
left ventricle myocardium	UBERON:0006566	79.10	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.86	gold quality
upper arm skin	UBERON:0004263	78.11	gold quality
trabecular bone tissue	UBERON:0002483	76.03	gold quality
kidney epithelium	UBERON:0004819	73.93	gold quality
adrenal tissue	UBERON:0018303	73.00	gold quality
colonic epithelium	UBERON:0000397	71.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.17	gold quality
mucosa of paranasal sinus	UBERON:0005030	69.55	gold quality
rectum	UBERON:0001052	69.54	gold quality
nasal cavity epithelium	UBERON:0005384	68.85	gold quality
myocardium	UBERON:0002349	68.51	gold quality
mucosa of transverse colon	UBERON:0004991	68.19	gold quality
small intestine	UBERON:0002108	67.42	gold quality
leukocyte	CL:0000738	65.75	gold quality
parietal pleura	UBERON:0002400	65.74	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	776.63
E-GEOD-75688	yes	530.64
E-CURD-122	yes	102.41
E-HCAD-4	yes	54.17
E-CURD-112	yes	40.74
E-ANND-3	yes	21.60
E-HCAD-10	yes	16.20
E-MTAB-9801	yes	6.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting FCRLA, 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-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-3944-5P	98.50	67.55	997

Literature-anchored findings (GeneRIF, showing 11)

• The concentration of FREB FCRL in patients with rheumatoid arthritis is three times higher than in healthy adults. (PMID:12966588)
• FCRL/FREB may function in melanocytes and melanoma and may be useful for development of diagnostic methods for various pigment disorders and immunotherapy of melanoma. (PMID:15551350)
• Analysis of human cell lines has confirmed that FcRLA is not secreted but is maintained as an intracellular protein in B cells where it interacts with immunoglobulins. (PMID:20668221)
• The studies reported here demonstrate that FCRLA is more broadly expressed among human B lineage cells than originally reported; it is found at significant levels in resting blood B cells and at varying levels in all B-cell subsets in tonsil. (PMID:21149418)
• alternative splicing of FCRLA mRNA results in the production of isoforms differing by their domain composition and possessing either the short or long signal peptide. (PMID:23742757)
• This first genome-wide association approach for cyclophosphamide response in lupus nephritis patients yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to cyclophosphamide metabolism and efficacy. (PMID:26980576)
• FCGR2C SNPs that associated with vaccine efficacy in RV144 also strongly associated with the expression of FCGR2A/C and one of them also associated with the expression of Fc receptor-like A (FCRLA), another Fc-gamma receptor (FcgammaR) gene (PMID:27015273)
• FCRLA-A Resident Endoplasmic Reticulum Protein that Associates with Multiple Immunoglobulin Isotypes in B Lineage Cells (PMID:28879521)
• FCRLA has long been viewed as a B cell specific protein, and this is the first time its expression has also been shown in human plasmacytoid dendritic cells (PMID:29236355)
• Development and Validation of the B Cell-Associated Fc Receptor-like Molecule-Based Prognostic Signature in Skin Cutaneous Melanoma. (PMID:32908921)
• Fc receptor-like A promotes malignant behavior in renal cell carcinoma and correlates with tumor immune infiltration. (PMID:39108036)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fcrla	ENSMUSG00000038421
rattus_norvegicus	Fcrla	ENSRNOG00000003136

Paralogs (17): FCGR2B (ENSG00000072694), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), FCRL3 (ENSG00000160856), FCRLB (ENSG00000162746), 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 A — Q7L513 (reviewed: Q7L513)

Alternative names: Fc receptor homolog expressed in B-cells, Fc receptor-like and mucin-like protein 1, Fc receptor-like protein, Fc receptor-related protein X

All UniProt accessions (2): Q7L513, Q5VXA5

UniProt curated annotations — full annotation on UniProt →

Function. May be implicated in B-cell differentiation and lymphomagenesis.

Subunit / interactions. Monomer or homodimer; disulfide-linked.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed specifically in primary and secondary lymphoid tissues like lymph node, spleen and tonsil. Specifically expressed in B-cells with a high level in normal germinal center B-cells, centroblasts and in a subset of diffuse large B-cell lymphomas. Highly expressed in bone marrow B-cells and weakly in earlier B lineage cells. Expressed in pre-germinal and germinal center B-cells in secondary lymphoid tissues. Also expressed in melanoma and melanocytes.

Isoforms (15)

UniProt ID	Names	Canonical?
Q7L513-1	1, FCRLa	yes
Q7L513-2	2, FCRLa1
Q7L513-3	3, FCRLb
Q7L513-4	4, FCRLc1
Q7L513-5	5, FCRLc2
Q7L513-6	6, FCRLd
Q7L513-7	7, FCRLe
Q7L513-8	8, FCRLf
Q7L513-9	9
Q7L513-10	10
Q7L513-11	11
Q7L513-12	12
Q7L513-13	13
Q7L513-14	14
Q7L513-15	15

RefSeq proteins (9): NP_001171795, NP_001171796, NP_001171799, NP_001171800, NP_001171801, NP_001171802, NP_001353124, NP_001353125, NP_116127* (*=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 (31 total): splice variant 8, strand 8, sequence conflict 4, domain 2, compositionally biased region 2, disulfide bond 2, signal peptide 1, chain 1, sequence variant 1, helix 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4HWN	X-RAY DIFFRACTION	2.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L513-F1	76.28	0.49

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): 99–143, 192–240

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOCC_CELL_SURFACE, CAGCTG_AP4_Q5, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, HOWLIN_PUBERTAL_MAMMARY_GLAND, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, ROZANOV_MMP14_TARGETS_UP, MODULE_301, GOBP_ADAPTIVE_IMMUNE_RESPONSE, PU1_Q6, SABATES_COLORECTAL_ADENOMA_DN

GO Biological Process (3): immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), cell differentiation (GO:0030154)

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

GO Cellular Component (2): cytoplasm (GO:0005737), external side of plasma membrane (GO:0009897)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	1
response to stimulus	1
signal transduction	1
cellular developmental process	1
signaling receptor activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCRLA	MEIS1	O00470	766
FCRLA	NUP98	P52948	718
FCRLA	HOXA9	P31269	718
FCRLA	VPREB3	Q9UKI3	653
FCRLA	MS4A2	Q01362	598
FCRLA	CD19	P15391	591
FCRLA	CD72	P21854	572
FCRLA	MS4A1	P08984	479
FCRLA	CD274	Q9NZQ7	443
FCRLA	NIBAN3	Q86XR2	436
FCRLA	IGSF23	A1L1A6	433
FCRLA	BLK	P51451	409
FCRLA	CD79B	P40259	406
FCRLA	PTPN11	Q06124	402
FCRLA	CD79A	P11912	394

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FCRLA	SNUPN	psi-mi:“MI:0915”(physical association)	0.400
	FCRLA	psi-mi:“MI:0915”(physical association)	0.000
FCRLA	aspA1	psi-mi:“MI:0915”(physical association)	0.000
tap	FCRLA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): FCRLA (Affinity Capture-MS), SNUPN (Affinity Capture-MS)

ESM2 similar proteins: A6NMB1, A7LCJ3, G1T7E7, G1TR84, M3XWH1, O15389, O43699, O70540, P04217, P05362, P0DP72, P13597, P20138, P32942, P33729, Q00238, Q08ET2, Q14773, Q28125, Q28730, Q28806, Q2KJF1, Q5NKT8, Q5NKU6, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q62230, Q64JA4, Q6DN72, Q7L513, Q80ZE3, Q91Y57, Q920A9, Q920G3, Q92154, Q95132, Q95LH0, Q96A28

Diamond homologs: A1YIY0, P12314, P23505, Q6DN72, Q7L513, Q96LA5, Q96LA6, Q96P31, Q96RD9, A0A0B4J1G0, A3RFZ7, E2RP87, G1T7E7, G1TR84, H0VDZ8, M3XWH1, O75015, P08101, P08508, P08637, P0DTI4, P12318, P12319, P12371, P20489, P26151, P27645, P31994, P31995, P79107, Q09TM2, Q09TM4, Q28110, Q28942, Q5DRQ8, Q60513, Q63203, Q6BAA4, Q6XPU4, Q8SPV8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161710422:A:AG	acceptor_gain	1.0000
1:161710423:T:G	acceptor_gain	1.0000
1:161710411:A:AG	acceptor_gain	0.9900
1:161710416:T:A	acceptor_gain	0.9900
1:161710422:AT:A	acceptor_gain	0.9900
1:161710423:T:TA	acceptor_gain	0.9900
1:161722621:T:G	acceptor_gain	0.9900
1:161725817:GCAG:G	acceptor_loss	0.9900
1:161725818:CA:C	acceptor_loss	0.9900
1:161725819:A:AG	acceptor_gain	0.9900
1:161725819:AGATT:A	acceptor_gain	0.9900
1:161725820:G:GG	acceptor_gain	0.9900
1:161725820:GATT:G	acceptor_gain	0.9900
1:161725820:GATTG:G	acceptor_gain	0.9900
1:161726064:C:G	donor_gain	0.9900
1:161710741:T:TA	acceptor_gain	0.9800
1:161710742:G:A	acceptor_gain	0.9800
1:161712217:GG:G	donor_gain	0.9800
1:161712218:GG:G	donor_gain	0.9800
1:161722626:T:G	acceptor_gain	0.9800
1:161723334:T:G	acceptor_gain	0.9800
1:161725820:GA:G	acceptor_gain	0.9800
1:161725820:GAT:G	acceptor_gain	0.9800
1:161722824:T:A	acceptor_gain	0.9700
1:161723398:T:G	acceptor_gain	0.9700
1:161723405:T:TA	acceptor_gain	0.9700
1:161725813:T:TA	acceptor_gain	0.9700
1:161710459:T:TA	acceptor_gain	0.9600
1:161711370:T:TA	acceptor_gain	0.9600
1:161721657:CACAG:C	donor_loss	0.9600

AlphaMissense

2431 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000559520 (1:161712904 A>G), RS1000930126 (1:161712590 A>G), RS1001016103 (1:161708733 C>A,T), RS1001401873 (1:161707537 T>C), RS1001880931 (1:161712382 C>A), RS1003026132 (1:161705806 T>A), RS1003415898 (1:161711346 C>T), RS1003531067 (1:161710714 G>C), RS1003536448 (1:161711095 C>A,G), RS1003595579 (1:161705254 G>A), RS1003793209 (1:161707891 G>A,T), RS1003866624 (1:161708164 CT>C), RS1003875191 (1:161709428 G>A), RS1004044682 (1:161713472 T>G), RS1005469540 (1:161709417 C>G,T)

Disease associations

OMIM: gene MIM:606891 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001725_37	Inflammatory bowel disease	2.000000e-38
GCST003445_14	Response to cyclophosphamide in systemic lupus erythematosus with lupus nephritis	3.000000e-08
GCST90002388_631	Lymphocyte count	8.000000e-14
GCST90002389_89	Lymphocyte percentage of white cells	2.000000e-10
GCST90013407_81	Liver enzyme levels (gamma-glutamyl transferase)	4.000000e-38

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004532	serum gamma-glutamyl transferase 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
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cadmium	increases abundance, increases expression, decreases expression	2
Doxorubicin	increases expression, decreases expression	2
Formaldehyde	increases expression, affects response to substance	2
bisphenol A	decreases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
CGP 52608	affects binding, increases reaction	1
Capecitabine	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Ethanol	decreases expression	1
Vehicle Emissions	decreases methylation	1
Benzene	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Mercury	decreases expression	1
Nickel	increases expression	1
Perfume	increases expression	1
Organophosphates	decreases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	increases abundance, decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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