FCRL1

Summary

FCRL1 (Fc receptor like 1, HGNC:18509) is a protein-coding gene on chromosome 1q23.1, encoding Fc receptor-like protein 1 (Q96LA6). Type I transmembrane surface glycoprotein preferentially expressed by B-cells that regulates BCR-mediated signaling responses.

This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains three extracellular C2-like immunoglobulin domains, a transmembrane domain and a cytoplasmic domain with two immunoreceptor-tyrosine activation motifs. This protein may play a role in the regulation of cancer cell growth. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 115350 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_052938

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18509
Approved symbol	FCRL1
Name	Fc receptor like 1
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FCRH1, IRTA5, IFGP1, CD307a
Ensembl gene	ENSG00000163534
Ensembl biotype	protein_coding
OMIM	606508
Entrez	115350

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000358292, ENST00000368175, ENST00000368176, ENST00000463001, ENST00000480310, ENST00000489998, ENST00000491942, ENST00000495126, ENST00000863016, ENST00000863017, ENST00000863018, ENST00000863019

RefSeq mRNA: 3 — MANE Select: NM_052938 NM_001159397, NM_001159398, NM_052938

CCDS: CCDS1170, CCDS53382, CCDS53383

Canonical transcript exons

ENST00000368176 — 11 exons

Exon	Start	End
ENSE00001075740	157802377	157802664
ENSE00001446494	157820007	157820120
ENSE00001951540	157794403	157796170
ENSE00002403580	157801915	157802193
ENSE00003497564	157807102	157807122
ENSE00003512727	157798161	157798243
ENSE00003516347	157800058	157800085
ENSE00003601457	157797868	157797939
ENSE00003614506	157803845	157804111
ENSE00003626105	157801461	157801577
ENSE00003671163	157797101	157797132

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 93.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.2792 / max 1078.3332, expressed in 127 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15283	4.1712	90
15284	2.0908	88
15285	0.0172	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	93.63	gold quality
spleen	UBERON:0002106	92.79	gold quality
lymph node	UBERON:0000029	91.48	gold quality
granulocyte	CL:0000094	90.88	gold quality
buccal mucosa cell	CL:0002336	89.98	gold quality
bone marrow cell	CL:0002092	85.95	gold quality
caecum	UBERON:0001153	83.81	gold quality
blood	UBERON:0000178	83.25	gold quality
bone marrow	UBERON:0002371	82.19	gold quality
epithelium of nasopharynx	UBERON:0001951	81.80	gold quality
ileal mucosa	UBERON:0000331	80.92	gold quality
tonsil	UBERON:0002372	78.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.62	gold quality
superficial temporal artery	UBERON:0001614	75.15	gold quality
leukocyte	CL:0000738	73.06	gold quality
monocyte	CL:0000576	71.63	gold quality
trabecular bone tissue	UBERON:0002483	71.15	silver quality
rectum	UBERON:0001052	70.99	gold quality
gall bladder	UBERON:0002110	70.97	gold quality
small intestine	UBERON:0002108	70.83	gold quality
colonic epithelium	UBERON:0000397	68.83	gold quality
upper lobe of left lung	UBERON:0008952	67.32	gold quality
upper lobe of lung	UBERON:0008948	66.75	gold quality
mucosa of transverse colon	UBERON:0004991	65.97	gold quality
right lung	UBERON:0002167	65.16	gold quality
vena cava	UBERON:0004087	63.34	gold quality
pancreatic ductal cell	CL:0002079	59.53	silver quality
lung	UBERON:0002048	59.35	gold quality
right lobe of liver	UBERON:0001114	59.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.05	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	68.27
E-ANND-3	yes	33.56
E-MTAB-9067	yes	16.57
E-MTAB-9801	yes	4.55
E-GEOD-111727	no	95.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

76 targeting FCRL1, 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-1193	100.00	65.93	529
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4316	99.37	65.75	1360

Literature-anchored findings (GeneRIF, showing 10)

• FcRH1 thus has the potential to serve as an activating coreceptor on B cells. (PMID:15479727)
• Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia. (PMID:18704934)
• Down-regulation of FCRL1 is associated with acute lymphoblastic leukemia. (PMID:18802695)
• Expression level of FCRL1 gene in peripheral blood B-lymphocytes is significantly higher in patients with autoimmune diseases. (PMID:22888639)
• Data show the Differences in high resolution melting analysis in promoters of tumor markers neuronal membrane glycoprotein M6-B, melanoma antigen family A12 and immunoglobulin superfamily Fc receptor indicated invasiveness of hepatocellular carcinoma. (PMID:23950870)
• FCRL1 gene expression down-regulates in both Hashimoto and Graves disease patients compared to normal subjects. (PMID:25738996)
• A Gene-Environment Interaction Between Smoking and Gene polymorphisms Provides a High Risk of Two Subgroups of Sarcoidosis. (PMID:31819081)
• Expression profile of Fc receptor-like molecules in patients with IgA nephropathy. (PMID:33597097)
• FCRL1 Regulates B Cell Receptor-Induced ERK Activation through GRB2. (PMID:34697226)
• FCRL1 immunoregulation in B cell development and malignancy. (PMID:37822931)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fcrl1	ENSMUSG00000059994
rattus_norvegicus	Fcrl1	ENSRNOG00000034230

Paralogs (17): FCGR2B (ENSG00000072694), FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), FCRL3 (ENSG00000160856), FCRLB (ENSG00000162746), FCGR3B (ENSG00000162747), FCRL4 (ENSG00000163518), FCER1A (ENSG00000179639), FCRL6 (ENSG00000181036), C17orf99 (ENSG00000187997), FCGR3A (ENSG00000203747), FCGR2C (ENSG00000244682), PECAM1 (ENSG00000261371), MILR1 (ENSG00000271605)

Protein

Protein identifiers

Fc receptor-like protein 1 — Q96LA6 (reviewed: Q96LA6)

Alternative names: Fc receptor homolog 1, IFGP family protein 1, Immune receptor translocation-associated protein 5

All UniProt accessions (1): Q96LA6

UniProt curated annotations — full annotation on UniProt →

Function. Type I transmembrane surface glycoprotein preferentially expressed by B-cells that regulates BCR-mediated signaling responses. Recruits ABL1 as the intracellular effector molecule to enhance B-cell activation. Also plays a negative role by suppressing ERK activation under homeostatic and BCR-stimulated conditions in a GRB2-dependent manner.

Subunit / interactions. Interacts with ABL1. Interacts with GRB2 and SOS1. Interacts with SHIP-1/INPP5D.

Subcellular location. Cell membrane.

Tissue specificity. Primarily expressed in secondary lymphoid tissues by mature subsets of B-cells. Detected in spleen, lymph node, heart, skeletal muscle, kidney, liver and placenta. Specifically expressed by mature B lineage cells with higher expression in naive versus memory B-cells (at protein level).

Post-translational modifications. Phosphorylated on tyrosines upon activation.

Induction. Down-regulated in activated B-cells.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96LA6-1	1	yes
Q96LA6-2	2
Q96LA6-3	3
Q96LA6-4	4

RefSeq proteins (3): NP_001152869, NP_001152870, NP_443170* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
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: PF13927

UniProt features (24 total): splice variant 6, short sequence motif 5, disulfide bond 3, domain 3, topological domain 2, signal peptide 1, chain 1, glycosylation site 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LA6-F1	75.57	0.54

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 (3): 38–86, 134–183, 229–276

Glycosylation sites (1): 293

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_B_CELL_ACTIVATION, GOCC_CELL_SURFACE, MODULE_301, MODULE_188, GOCC_SIDE_OF_MEMBRANE, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_CORECEPTOR_ACTIVITY, SENGUPTA_EBNA1_ANTICORRELATED, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_EXTERNAL_SIDE_OF_PLASMA_MEMBRANE, GOBP_LYMPHOCYTE_ACTIVATION, RAO_BOUND_BY_SALL4_ISOFORM_B, GSE13522_WT_VS_IFNAR_KO_SKIN_DN, CREBL2_TARGET_GENES

GO Biological Process (3): immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), B cell activation (GO:0042113)

GO Molecular Function (2): transmembrane signaling receptor activity (GO:0004888), coreceptor activity (GO:0015026)

GO Cellular Component (4): external side of plasma membrane (GO:0009897), cell surface (GO:0009986), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor activity	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
signal transduction	1
lymphocyte activation	1
plasma membrane	1
cell surface	1
side of membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCRL1	PIGR	P01833	750
FCRL1	FCGR1A	P12314	736
FCRL1	FCGR3A	P08637	607
FCRL1	FCGR3B	O75015	604
FCRL1	FCGR2B	P31994	578
FCRL1	FCRL4	Q96PJ5	517
FCRL1	MUC1	P13931	497
FCRL1	BCL9	O00512	424
FCRL1	FCAMR	Q8WWV6	368
FCRL1	TAS2R60	P59551	320
FCRL1	PTPN6	P29350	317
FCRL1	PTPN11	Q06124	303
FCRL1	SIGLEC5	O15389	300
FCRL1	FCGR2A	P12318	278
FCRL1	CD5L	O43866	278

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FCRL1	MYADM	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): APOD (Affinity Capture-MS), MYADM (Affinity Capture-MS)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

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, Q3B8P2, Q5DRQ8, Q60513, Q63203, Q68SN8, Q6BAA4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1560 predictions. Top by Δscore:

Variant	Effect	Δscore
1:157797098:TAC:T	donor_loss	1.0000
1:157797099:ACCT:A	donor_loss	1.0000
1:157797100:C:CG	donor_loss	1.0000
1:157797128:TTCTG:T	acceptor_gain	1.0000
1:157797129:TCTG:T	acceptor_loss	1.0000
1:157797130:CTG:C	acceptor_gain	1.0000
1:157797130:CTGC:C	acceptor_loss	1.0000
1:157797131:TGCTG:T	acceptor_loss	1.0000
1:157797132:GC:G	acceptor_loss	1.0000
1:157797133:C:CC	acceptor_gain	1.0000
1:157797757:ACAG:A	donor_gain	1.0000
1:157797758:CAGC:C	donor_gain	1.0000
1:157798241:CTC:C	acceptor_gain	1.0000
1:157798242:TCC:T	acceptor_loss	1.0000
1:157798243:CCTG:C	acceptor_loss	1.0000
1:157798244:C:CC	acceptor_gain	1.0000
1:157798244:CT:C	acceptor_loss	1.0000
1:157798245:T:A	acceptor_loss	1.0000
1:157797099:A:AC	donor_gain	0.9900
1:157797100:C:CC	donor_gain	0.9900
1:157797131:TG:T	acceptor_gain	0.9900
1:157797133:C:A	acceptor_loss	0.9900
1:157797134:T:C	acceptor_loss	0.9900
1:157797758:CAG:C	donor_gain	0.9900
1:157798154:GGCTC:G	donor_loss	0.9900
1:157798155:GCTCA:G	donor_loss	0.9900
1:157798156:CTCA:C	donor_loss	0.9900
1:157798158:CACCA:C	donor_loss	0.9900
1:157798239:GGCTC:G	acceptor_gain	0.9900
1:157798242:TC:T	acceptor_gain	0.9900

AlphaMissense

2769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:157802583:C:G	C134S	0.985
1:157802584:A:T	C134S	0.985
1:157802584:A:G	C134R	0.983
1:157802582:G:C	C134W	0.981
1:157802583:C:T	C134Y	0.981
1:157802543:C:A	W147C	0.977
1:157802543:C:G	W147C	0.977
1:157802545:A:G	W147R	0.977
1:157802545:A:T	W147R	0.977
1:157802436:C:G	C183S	0.975
1:157802437:A:T	C183S	0.975
1:157801974:C:G	C276S	0.971
1:157801975:A:T	C276S	0.971
1:157802115:C:G	C229S	0.969
1:157802116:A:T	C229S	0.969
1:157803907:C:G	C86S	0.969
1:157803908:A:T	C86S	0.969
1:157802549:G:C	F145L	0.968
1:157802549:G:T	F145L	0.968
1:157802551:A:G	F145L	0.968
1:157802435:A:C	C183W	0.967
1:157802436:C:T	C183Y	0.967
1:157802115:C:T	C229Y	0.965
1:157804008:G:C	F52L	0.965
1:157804008:G:T	F52L	0.965
1:157804010:A:G	F52L	0.965
1:157801974:C:T	C276Y	0.962
1:157802437:A:G	C183R	0.961
1:157801969:C:G	A278P	0.958
1:157804002:A:C	F54L	0.958

dbSNP variants (sampled 300 via entrez): RS1000133381 (1:157816348 A>G), RS1000143651 (1:157808106 C>A), RS1000202142 (1:157794230 CTG>C), RS1000522244 (1:157811776 C>T), RS1000636876 (1:157811300 G>T), RS1000677482 (1:157817597 C>A), RS1000687895 (1:157799763 C>T), RS1000798086 (1:157805601 A>G), RS1001194862 (1:157808595 G>A), RS1001453305 (1:157794755 T>C), RS1001453637 (1:157795936 C>A,T), RS1001462269 (1:157821179 G>A), RS1001512766 (1:157820976 C>G), RS1001613621 (1:157795530 T>C), RS1001710268 (1:157814616 A>G)

Disease associations

OMIM: gene MIM:606508 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005531_30	Multiple sclerosis	2.000000e-10
GCST006585_2819	Blood protein levels	3.000000e-30

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
Amiodarone	increases expression	1
Arsenic	affects expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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