PILRB

Summary

PILRB (paired immunoglobin like type 2 receptor beta, HGNC:18297) is a protein-coding gene on chromosome 7q22.1, encoding Paired immunoglobulin-like type 2 receptor beta (Q9UKJ0). Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system.

The paired immunoglobin-like type 2 receptors consist of highly related activating and inhibitory receptors that are involved in the regulation of many aspects of the immune system. The paired immunoglobulin-like receptor genes are located in a tandem head-to-tail orientation on chromosome 7. This gene encodes the activating member of the receptor pair and contains a truncated cytoplasmic tail relative to its inhibitory counterpart (PILRA), that has a long cytoplasmic tail with immunoreceptor tyrosine-based inhibitory (ITIM) motifs. This gene is thought to have arisen from a duplication of the inhibitory PILRA gene and evolved to acquire its activating function.

Source: NCBI Gene 29990 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_178238

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18297
Approved symbol	PILRB
Name	paired immunoglobin like type 2 receptor beta
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FDFACT1, FDFACT2
Ensembl gene	ENSG00000121716
Ensembl biotype	protein_coding
OMIM	605342
Entrez	29990

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 retained_intron

ENST00000419749, ENST00000422808, ENST00000431140, ENST00000438028, ENST00000438231, ENST00000443526, ENST00000448382, ENST00000452089, ENST00000455145, ENST00000457519, ENST00000493091, ENST00000608825, ENST00000609309

RefSeq mRNA: 2 — MANE Select: NM_178238 NM_001371931, NM_178238

CCDS: CCDS43622

Canonical transcript exons

ENST00000609309 — 4 exons

Exon	Start	End
ENSE00003705742	100358117	100358366
ENSE00003709508	100367349	100367831
ENSE00003731697	100358690	100359079
ENSE00003740584	100359337	100359537

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0635 / max 14.8748, expressed in 13 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79951	0.0635	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.78	gold quality
left testis	UBERON:0004533	98.58	gold quality
right uterine tube	UBERON:0001302	98.47	gold quality
pituitary gland	UBERON:0000007	98.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.23	gold quality
adenohypophysis	UBERON:0002196	98.21	gold quality
cerebellar hemisphere	UBERON:0002245	98.17	gold quality
cerebellar cortex	UBERON:0002129	98.14	gold quality
cerebellum	UBERON:0002037	98.10	gold quality
right lobe of thyroid gland	UBERON:0001119	98.04	gold quality
metanephros cortex	UBERON:0010533	97.64	gold quality
left lobe of thyroid gland	UBERON:0001120	97.40	gold quality
thyroid gland	UBERON:0002046	97.07	gold quality
granulocyte	CL:0000094	97.05	gold quality
spleen	UBERON:0002106	96.87	gold quality
testis	UBERON:0000473	96.81	gold quality
right lobe of liver	UBERON:0001114	96.80	gold quality
mucosa of transverse colon	UBERON:0004991	96.63	gold quality
fundus of stomach	UBERON:0001160	96.59	gold quality
right adrenal gland cortex	UBERON:0035827	96.38	gold quality
endocervix	UBERON:0000458	96.26	gold quality
right ovary	UBERON:0002118	96.10	gold quality
left adrenal gland cortex	UBERON:0035825	95.92	gold quality
prostate gland	UBERON:0002367	95.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.76	gold quality
right adrenal gland	UBERON:0001233	95.63	gold quality
body of pancreas	UBERON:0001150	95.57	gold quality
left ovary	UBERON:0002119	95.57	gold quality
left adrenal gland	UBERON:0001234	95.45	gold quality
body of stomach	UBERON:0001161	95.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-53	no	664.93
E-ANND-3	no	2.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting PILRB, 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-548P	99.98	72.25	3784
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-337-3P	97.90	69.37	1052
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-151A-5P	95.79	68.73	162
HSA-MIR-151B	95.79	68.73	162
HSA-MIR-6784-5P	84.56	60.91	126

Literature-anchored findings (GeneRIF, showing 4)

• Characterization of paired counterpart PILRA. (PMID:10903717)
• PILRbeta differs from PILRalpha in one of the three residues (Y2, R95 and W108) on the surface of PILRalpha (L108), explaining its inability to engage gB. (PMID:24843130)
• HACS1 signaling adaptor protein recognizes a motif in the paired immunoglobulin receptor B cytoplasmic domain. (PMID:33188360)
• PILRB potentiates the PI3K/AKT signaling pathway and reprograms cholesterol metabolism to drive gastric tumorigenesis and metastasis. (PMID:39227585)

Cross-species orthologs

0 orthologs

Paralogs (1): PILRA (ENSG00000085514)

Protein

Protein identifiers

Paired immunoglobulin-like type 2 receptor beta — Q9UKJ0 (reviewed: Q9UKJ0)

Alternative names: Activating receptor PILR-beta, Cell surface receptor FDFACT

All UniProt accessions (7): C9J8P3, C9JGQ4, C9JNA4, C9JPU0, C9JTD2, Q9UKJ0, V9GYC2

UniProt curated annotations — full annotation on UniProt →

Function. Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRB is thought to act as a cellular signaling activating receptor that associates with ITAM-bearing adapter molecules on the cell surface.

Subcellular location. Membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UKJ0-1	1	yes
Q9UKJ0-2	2
Q9UKJ0-3	3

RefSeq proteins (2): NP_001358860, NP_839956* (*=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
IPR051694	Immunoregulatory_rcpt-like	Family

UniProt features (26 total): strand 10, sequence variant 2, sequence conflict 2, helix 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, turn 1, transmembrane region 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4NFD	X-RAY DIFFRACTION	1.71
4NFC	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKJ0-F1	81.09	0.60

Functional residue map

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

Glycosylation sites (1): 100

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

MSigDB gene sets: 132 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, ONKEN_UVEAL_MELANOMA_UP, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GATA3_01, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GATA1_01, MODULE_480, AMIT_EGF_RESPONSE_20_HELA, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, HESS_TARGETS_OF_HOXA9_AND_MEIS1_DN, GATA1_02, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (2): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), activation of transmembrane receptor protein tyrosine kinase activity (GO:0007171)

GO Molecular Function (2): MHC class I protein binding (GO:0042288), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
enzyme-linked receptor protein signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
activation of protein kinase activity	1
protein-containing complex assembly	1
MHC protein binding	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PILRB	CD99L2	Q8TCZ2	936
PILRB	LAIR1	Q6GTX8	763
PILRB	CD99	P14209	759
PILRB	KLRG1	Q96E93	668
PILRB	LILRB1	Q8NHL6	646
PILRB	ZCWPW1	Q9H0M4	596
PILRB	PILRA	Q9UKJ1	584
PILRB	CD300C	Q08708	572
PILRB	GYPC	P04921	528
PILRB	TNFRSF14	Q92956	511
PILRB	NYAP1	Q6ZVC0	510
PILRB	SPACDR	Q8IZ16	473
PILRB	NECTIN1	Q15223	453
PILRB	ARMS2	P0C7Q2	446
PILRB	PTPN11	Q06124	440

IntAct

11 interactions, top by confidence:

A	B	Type	Score
IL1RAPL1	PILRB	psi-mi:“MI:0915”(physical association)	0.400
LILRA3	PILRB	psi-mi:“MI:0915”(physical association)	0.400
MXRA5	PILRB	psi-mi:“MI:0915”(physical association)	0.400
ILDR1	PILRB	psi-mi:“MI:0915”(physical association)	0.400
PILRB	AXL	psi-mi:“MI:0915”(physical association)	0.400
PILRA	PODXL	psi-mi:“MI:0914”(association)	0.350
PILRB	EI24	psi-mi:“MI:0914”(association)	0.350
PILRB	menB	psi-mi:“MI:0915”(physical association)	0.000
PILRB	katG	psi-mi:“MI:0915”(physical association)	0.000
ABHD16A	PILRB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): PILRB (Affinity Capture-MS), PILRB (Affinity Capture-MS), PILRB (Affinity Capture-RNA), PILRB (Affinity Capture-RNA), KDSR (Affinity Capture-MS), ATP6AP1 (Affinity Capture-MS), RTN4 (Affinity Capture-MS), TSPAN15 (Affinity Capture-MS), ATP6AP2 (Affinity Capture-MS), YIF1B (Affinity Capture-MS), ATP5L (Affinity Capture-MS), EI24 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), NME2 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS)

ESM2 similar proteins: A2A7V7, A2TGX5, A5D7B2, G3X8R9, O88875, O95944, P0DMS9, P11912, P12318, P15530, P16410, P22273, P31785, P31994, P31995, P34902, P40259, P50283, Q02242, Q1ERP8, Q2LA85, Q2YFS1, Q2YFS2, Q2YFS3, Q3LRV9, Q3U497, Q566E6, Q5T2D2, Q60513, Q6SJQ0, Q6SJQ5, Q6SJQ7, Q6TYI6, Q6UXG3, Q6UXN2, Q7TSN2, Q86YW5, Q8K558, Q8SPV8, Q8TDQ1

Diamond homologs: Q2YFS1, Q2YFS2, Q2YFS3, Q9UKJ0, Q9UKJ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1592 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100352475:GCAG:G	donor_gain	1.0000
7:100352476:CAGGT:C	donor_loss	1.0000
7:100352477:AGGT:A	donor_loss	1.0000
7:100352478:GGTG:G	donor_loss	1.0000
7:100352479:G:GG	donor_gain	1.0000
7:100352479:GTG:G	donor_loss	1.0000
7:100352474:TGCAG:T	donor_gain	0.9900
7:100352475:GCAGG:G	donor_gain	0.9900
7:100352476:CAG:C	donor_gain	0.9900
7:100358362:GCCTG:G	donor_gain	0.9900
7:100359076:CAGGG:C	donor_loss	0.9900
7:100359078:GG:G	donor_gain	0.9900
7:100359079:GG:G	donor_gain	0.9900
7:100359079:GGTG:G	donor_loss	0.9900
7:100359080:GTG:G	donor_loss	0.9900
7:100359081:TGAG:T	donor_loss	0.9900
7:100359082:GA:G	donor_loss	0.9900
7:100352480:T:A	donor_loss	0.9800
7:100352562:A:AG	acceptor_gain	0.9800
7:100352562:AG:A	acceptor_gain	0.9800
7:100352563:G:GG	acceptor_gain	0.9800
7:100352563:GG:G	acceptor_gain	0.9800
7:100352992:CCCA:C	acceptor_loss	0.9800
7:100352993:CCAG:C	acceptor_loss	0.9800
7:100352994:CA:C	acceptor_loss	0.9800
7:100352995:A:G	acceptor_loss	0.9800
7:100356882:GG:G	donor_gain	0.9800
7:100356883:GG:G	donor_gain	0.9800
7:100358366:GGTGA:G	donor_loss	0.9800
7:100358685:TCTA:T	acceptor_loss	0.9800

AlphaMissense

1445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100358995:T:C	F124L	0.978
7:100358997:C:A	F124L	0.978
7:100358997:C:G	F124L	0.978
7:100358960:T:C	I112T	0.977
7:100358782:T:C	F53L	0.976
7:100358784:C:A	F53L	0.976
7:100358784:C:G	F53L	0.976
7:100358788:T:C	F55L	0.966
7:100358790:C:A	F55L	0.966
7:100358790:C:G	F55L	0.966
7:100358777:T:C	I51T	0.965
7:100358981:A:C	D119A	0.946
7:100358851:T:C	F76L	0.938
7:100358853:C:A	F76L	0.938
7:100358853:C:G	F76L	0.938
7:100358831:T:C	I69T	0.935
7:100358960:T:G	I112S	0.935
7:100358836:T:A	W71R	0.934
7:100358836:T:C	W71R	0.934
7:100358980:G:C	D119H	0.923
7:100358982:C:A	D119E	0.921
7:100358982:C:G	D119E	0.921
7:100358838:G:C	W71C	0.918
7:100358838:G:T	W71C	0.918
7:100358981:A:T	D119V	0.918
7:100358866:T:C	F81L	0.916
7:100358868:C:A	F81L	0.916
7:100358868:C:G	F81L	0.916
7:100359055:G:T	G144W	0.914
7:100358928:G:C	W101C	0.910

dbSNP variants (sampled 300 via entrez): RS1000169297 (7:100365958 T>G), RS1000224503 (7:100359955 A>G), RS1000574546 (7:100356490 G>T), RS1000629134 (7:100361631 T>A), RS1000924444 (7:100356697 C>T), RS1001569671 (7:100365931 G>A), RS1001629617 (7:100360405 G>A), RS1001733155 (7:100361502 G>A), RS1002152960 (7:100368134 G>A), RS1002337682 (7:100362876 G>A), RS1003240406 (7:100362792 G>A), RS1003393914 (7:100364217 C>T), RS1003579351 (7:100363165 C>G), RS1003749580 (7:100364467 G>C), RS1003856303 (7:100359916 A>G)

Disease associations

OMIM: gene MIM:605342 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003219_48	Advanced age-related macular degeneration	5.000000e-09
GCST003262_1112	Post bronchodilator FEV1	5.000000e-06
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15
GCST010796_3292	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST90002384_151	Hemoglobin	4.000000e-28
GCST90002393_69	Monocyte count	5.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004314	forced expiratory volume
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0004509	hemoglobin measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	increases expression, increases abundance, affects cotreatment	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Cycloheximide	increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Polychlorinated Biphenyls	affects expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cyclosporine	affects expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	increases expression	1
Genistein	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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