FCRL6

Summary

FCRL6 (Fc receptor like 6, HGNC:31910) is a protein-coding gene on chromosome 1q23.2, encoding Fc receptor-like protein 6 (Q6DN72). Acts as a MHC class II receptor.

Enables MHC class II protein binding activity and protein phosphatase binding activity. Predicted to be involved in cell surface receptor signaling pathway and immune response. Located in external side of plasma membrane.

Source: NCBI Gene 343413 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 100 total
• MANE Select transcript: NM_001004310

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31910
Approved symbol	FCRL6
Name	Fc receptor like 6
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	IFGP6, FLJ16056, FcRH6
Ensembl gene	ENSG00000181036
Ensembl biotype	protein_coding
OMIM	613562
Entrez	343413

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000321935, ENST00000339348, ENST00000368106, ENST00000392235, ENST00000536257, ENST00000540741, ENST00000541729, ENST00000882520, ENST00000882521

RefSeq mRNA: 9 — MANE Select: NM_001004310 NM_001004310, NM_001284217, NM_001426231, NM_001426232, NM_001426233, NM_001426234, NM_001426235, NM_001426236, NM_001426237

CCDS: CCDS30912, CCDS60312

Canonical transcript exons

ENST00000368106 — 10 exons

Exon	Start	End
ENSE00001282443	159808961	159809245
ENSE00001366175	159809402	159809683
ENSE00001408728	159813489	159813554
ENSE00001409269	159810094	159810216
ENSE00001409854	159815428	159815459
ENSE00001410178	159814221	159814292
ENSE00001433799	159808178	159808444
ENSE00001611812	159815536	159816257
ENSE00003572587	159806596	159806616
ENSE00003842591	159802360	159802455

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 98.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9949 / max 265.5525, expressed in 86 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5990	1.8563	83
5991	0.1386	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.04	gold quality
thymus	UBERON:0002370	87.78	silver quality
blood	UBERON:0000178	85.11	gold quality
spleen	UBERON:0002106	78.53	gold quality
lymph node	UBERON:0000029	77.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.18	gold quality
bone marrow	UBERON:0002371	71.87	gold quality
vermiform appendix	UBERON:0001154	71.56	gold quality
leukocyte	CL:0000738	71.10	gold quality
gall bladder	UBERON:0002110	70.08	gold quality
bone marrow cell	CL:0002092	69.52	silver quality
quadriceps femoris	UBERON:0001377	69.42	gold quality
monocyte	CL:0000576	68.69	gold quality
cerebellar vermis	UBERON:0004720	67.75	gold quality
smooth muscle tissue	UBERON:0001135	66.31	gold quality
duodenum	UBERON:0002114	66.22	gold quality
upper lobe of left lung	UBERON:0008952	65.90	gold quality
right lobe of liver	UBERON:0001114	64.68	gold quality
lung	UBERON:0002048	64.43	gold quality
liver	UBERON:0002107	64.27	gold quality
endometrium	UBERON:0001295	62.10	gold quality
colonic epithelium	UBERON:0000397	62.07	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.76	gold quality
rectum	UBERON:0001052	61.38	gold quality
right lung	UBERON:0002167	61.30	gold quality
subcutaneous adipose tissue	UBERON:0002190	60.35	gold quality
small intestine	UBERON:0002108	60.30	gold quality
adipose tissue	UBERON:0001013	60.13	gold quality
fallopian tube	UBERON:0003889	60.01	gold quality
tonsil	UBERON:0002372	59.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.29
E-GEOD-106540	no	880.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

31 targeting FCRL6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-34C-3P	98.11	65.60	858
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-144-5P	97.66	69.90	531
HSA-MIR-675-3P	95.77	69.27	675
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-1268A	87.06	61.46	145

Literature-anchored findings (GeneRIF, showing 2)

• FCRL6 is a distinct indicator of cytotoxic effector lymphocytes that is upregulated in diseases characterized by chronic immune stimulation. (PMID:18991291)
• Human FCRL6 receptor, selectively expressed by cytotoxic T and natural killer (NK) cells, directly binds the major histocompatibility complex (MHC) class II molecule HLA-DR. (PMID:20519654)

Cross-species orthologs

0 orthologs

Paralogs (17): FCGR2B (ENSG00000072694), FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), FCRL3 (ENSG00000160856), FCRLB (ENSG00000162746), FCGR3B (ENSG00000162747), FCRL4 (ENSG00000163518), FCRL1 (ENSG00000163534), FCER1A (ENSG00000179639), C17orf99 (ENSG00000187997), FCGR3A (ENSG00000203747), FCGR2C (ENSG00000244682), PECAM1 (ENSG00000261371), MILR1 (ENSG00000271605)

Protein

Protein identifiers

Fc receptor-like protein 6 — Q6DN72 (reviewed: Q6DN72)

Alternative names: Fc receptor homolog 6, IFGP6

All UniProt accessions (2): F5GYB3, Q6DN72

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a MHC class II receptor. When stimulated on its own, does not play a role in cytokine production or the release of cytotoxic granules by NK cells and cytotoxic CD8(+) T cells. Does not act as an Fc receptor.

Subunit / interactions. Interacts (tyrosine phosphorylated) with PTPN11. Interacts (tyrosine phosphorylated) with PTPN6, INPP5D, INPPL1 and GRB2. Interacts with class II MHC HLA-DR when the alpha chain is associated with a beta-1, beta-4 or a beta-5 but not a beta-3 chain.

Subcellular location. Cell membrane.

Tissue specificity. Expressed by cytolytic cells including NK cells, effector and effector-memory CD8(+) T-cells, and a subset of NKT cells (at protein level). Also expressed in gamma delta T cells and in a rare subset of effector CD4(+) T-cells (at protein level). Expressed in spleen, skin, peripheral blood leukocytes, liver, lung, bone marrow, small intestine and placenta. Expression among T-cells is greatly expanded in HIV-1 infected individuals, and includes not only effector and effector-memory CD8(+) T-cells but also populations of CD4(+) T-cells. Expression among CD8(+) T-cells and NK cells is expanded in individuals with chronic lymphocytic leukemia (CLL) but is reduced in PBMCs from patients with acute (AML), chronic myeloid leukemia (CML) and non-Hodgkin’s lymphoma. Expression is higher in PBMCs and/or CD3(+) cells of patients with autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and idiopathic thrombocytopenia purpura (ITP). In contrast, expression in CD3(+) cells from patients with lupus anticoagulans (LA) is higher.

Post-translational modifications. Phosphorylated on Tyr residues. Tyrosine phosphorylation induces association with phosphatase PTPN11, PTPN6, INPP5D, INPPL1 and GRB2.

Domain organisation. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif is involved in PTPN11 binding.

Induction. Down-regulated upon stimulation with mitogen phytohaemagglutinin (PHA) or concavalin A in peripheral blood mononuclear cells (PBMCs).

Isoforms (4)

UniProt ID	Names	Canonical?
Q6DN72-1	1, FCRL6v1	yes
Q6DN72-2	2
Q6DN72-3	3, FCRL6v4
Q6DN72-4	4

RefSeq proteins (9): NP_001004310, NP_001271146, NP_001413160, NP_001413161, NP_001413162, NP_001413163, NP_001413164, NP_001413165, NP_001413166 (=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: PF13895, PF13927

UniProt features (29 total): splice variant 6, sequence conflict 5, disulfide bond 3, domain 3, glycosylation site 2, topological domain 2, mutagenesis site 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6DN72-F1	76.29	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 371

Disulfide bonds (3): 39–83, 132–180, 228–276

Glycosylation sites (2): 65, 273

Mutagenesis-validated functional residues (2):

Position	Phenotype
356	no change of phosphorylation implicated in interaction with ptpn11. loss of interaction with inppd5, inppl1 and grb2.
371	loss of phosphorylation implicated in interaction with ptpn11. loss of interaction with ptpn11, ptpn6 and inppl1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GOCC_CELL_SURFACE, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_SIDE_OF_MEMBRANE, GOMF_PROTEIN_PHOSPHATASE_BINDING, GOMF_PHOSPHATASE_BINDING, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_MHC_PROTEIN_BINDING, GOCC_EXTERNAL_SIDE_OF_PLASMA_MEMBRANE, GOMF_MHC_CLASS_II_PROTEIN_BINDING, MIR6867_5P, AIZARANI_LIVER_C1_NK_NKT_CELLS_1, HAY_BONE_MARROW_NK_CELLS, BUSSLINGER_GASTRIC_IMMUNE_CELLS, DESCARTES_FETAL_KIDNEY_LYMPHOID_CELLS, BDP1_TARGET_GENES

GO Biological Process (2): immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), phosphatase binding (GO:0019902), protein phosphatase binding (GO:0019903), MHC class II protein binding (GO:0042289), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
immune system process	1
response to stimulus	1
signal transduction	1
signaling receptor activity	1
enzyme binding	1
phosphatase binding	1
MHC protein binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCRL6	FAM167B	Q9BTA0	481
FCRL6	SLAMF8	Q9P0V8	478
FCRL6	MFAP1	P55081	435
FCRL6	GZMB	P10144	413
FCRL6	PIGR	P01833	407
FCRL6	FGFBP2	Q9BYJ0	392
FCRL6	COL9A2	Q14055	384
FCRL6	NKG7	Q16617	373
FCRL6	CCHCR1	Q8TD31	369
FCRL6	ICE2	Q659A1	367
FCRL6	PARD3B	Q8TEW8	363
FCRL6	FCRLA	Q7L513	353
FCRL6	JCHAIN	P01591	353
FCRL6	CTSW	P56202	348
FCRL6	FRMD5	Q7Z6J6	346

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GALNT15	FCRL6	psi-mi:“MI:0915”(physical association)	0.560
FCRL6	GALNT15	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (2): FCRL6 (Two-hybrid), FCRL6 (Negative Genetic)

ESM2 similar proteins: A0A0B4J1G0, A0A0G2KBC9, A3RFZ7, B6A8R8, E2RP87, G1T7E7, G1TR84, H0VDZ8, M3XWH1, O75015, P08101, P08508, P08637, P0DTI4, P12314, P12318, P12319, P12371, P13597, P13598, P20489, P26151, P27645, P31995, P35330, P50283, P51866, P79107, P82957, Q00238, Q08481, Q09TM2, Q09TM4, Q14952, Q28942, Q3B8P2, Q3SWT0, Q5NKV1, Q5NKV2, Q60513

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, Q68SN8, Q6BAA4, Q6XPU4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SPI1	“up-regulates quantity by expression”	FCRL6	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1590 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159806594:A:AG	acceptor_gain	0.9900
1:159806595:G:GG	acceptor_gain	0.9900
1:159814219:A:AG	acceptor_gain	0.9900
1:159814220:G:GG	acceptor_gain	0.9900
1:159806617:G:GG	donor_gain	0.9800
1:159806618:TAAGT:T	donor_loss	0.9800
1:159815426:A:AG	acceptor_gain	0.9800
1:159815427:G:GG	acceptor_gain	0.9800
1:159815427:GCCA:G	acceptor_gain	0.9800
1:159806590:TTGCA:T	acceptor_loss	0.9700
1:159806591:TGCA:T	acceptor_loss	0.9700
1:159806592:GCAGT:G	acceptor_loss	0.9700
1:159806593:CAGTT:C	acceptor_loss	0.9700
1:159806594:AGTT:A	acceptor_loss	0.9700
1:159806595:G:T	acceptor_loss	0.9700
1:159806619:AAGTT:A	donor_loss	0.9700
1:159814220:GTGC:G	acceptor_gain	0.9700
1:159806591:TGCAG:T	donor_loss	0.9600
1:159808176:A:AG	acceptor_gain	0.9600
1:159808177:G:GG	acceptor_gain	0.9600
1:159815427:GC:G	acceptor_gain	0.9600
1:159815427:GCC:G	acceptor_gain	0.9600
1:159802496:GGACC:G	donor_gain	0.9500
1:159802497:GACCG:G	donor_gain	0.9500
1:159806594:AGTTC:A	donor_loss	0.9500
1:159814220:GT:G	acceptor_gain	0.9500
1:159806595:G:A	donor_loss	0.9400
1:159806614:CTGG:C	acceptor_loss	0.9400
1:159806615:TGG:T	acceptor_loss	0.9400
1:159810213:GCTG:G	donor_gain	0.9400

AlphaMissense

2799 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159809218:A:C	S193R	0.960
1:159809220:C:A	S193R	0.960
1:159809220:C:G	S193R	0.960
1:159809479:T:A	C228S	0.953
1:159809480:G:C	C228S	0.953
1:159808279:T:C	F52L	0.947
1:159808281:C:A	F52L	0.947
1:159808281:C:G	F52L	0.947
1:159809518:T:C	F241L	0.945
1:159809520:C:A	F241L	0.945
1:159809520:C:G	F241L	0.945
1:159808240:T:A	C39S	0.943
1:159808241:G:C	C39S	0.943
1:159809086:T:C	F149L	0.937
1:159809088:C:A	F149L	0.937
1:159809088:C:G	F149L	0.937
1:159808213:T:C	F30L	0.933
1:159808215:T:A	F30L	0.933
1:159808215:T:G	F30L	0.933
1:159809637:C:A	N280K	0.931
1:159809637:C:G	N280K	0.931
1:159808966:T:C	F109L	0.929
1:159808968:T:A	F109L	0.929
1:159808968:T:G	F109L	0.929
1:159809035:T:A	C132S	0.926
1:159809036:G:C	C132S	0.926
1:159809179:T:A	C180S	0.921
1:159809180:G:C	C180S	0.921
1:159809480:G:A	C228Y	0.920
1:159808372:T:A	C83S	0.915

dbSNP variants (sampled 300 via entrez): RS1000197082 (1:159813977 C>T), RS1000226973 (1:159800697 T>A,C), RS1000436174 (1:159803650 C>T), RS1000440258 (1:159803334 G>A), RS1000564714 (1:159814933 C>T), RS1000631274 (1:159813738 G>C), RS1000828999 (1:159802219 C>T), RS1000833374 (1:159807806 G>T), RS1000848743 (1:159803207 G>A,T), RS1000936880 (1:159815194 G>A), RS1001008288 (1:159809904 T>A,C), RS1001441586 (1:159804569 T>C), RS1001602177 (1:159812950 T>A), RS1001639529 (1:159806036 C>T), RS1001887630 (1:159801547 T>G)

Disease associations

OMIM: gene MIM:613562 | disease phenotypes: MIM:616414

GenCC curated gene-disease

Mondo (1): autoimmune interstitial lung disease-arthritis syndrome (MONDO:0014629)

Orphanet (1): Autoimmune interstitial lung disease-arthritis syndrome (Orphanet:444092)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001650_1	C-reactive protein	1.000000e-37
GCST001650_11	C-reactive protein	3.000000e-10
GCST001650_8	C-reactive protein	4.000000e-73
GCST009391_1659	Metabolite levels	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0010469	carnitine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Diuron	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Dronabinol	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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