MS4A2

Summary

MS4A2 (membrane spanning 4-domains A2, HGNC:7316) is a protein-coding gene on chromosome 11q12.1, encoding High affinity immunoglobulin epsilon receptor subunit beta (Q01362). High affinity receptor that binds to the Fc region of immunoglobulins epsilon.

The allergic response involves the binding of allergen to receptor-bound IgE followed by cell activation and the release of mediators responsible for the manifestations of allergy. The IgE-receptor, a tetramer composed of an alpha, beta, and 2 disulfide-linked gamma chains, is found on the surface of mast cells and basophils. This gene encodes the beta subunit of the high affinity IgE receptor which is a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This family member is localized to 11q12, among a cluster of membrane-spanning 4A gene family members. Alternative splicing results in multiple transcript variants encoding distinct proteins. Additional transcript variants have been described but require experimental validation.

Source: NCBI Gene 2206 — RefSeq curated summary.

At a glance

• Gene–disease (curated): IgE responsiveness, atopic (No Known Disease Relationship, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_000139

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7316
Approved symbol	MS4A2
Name	membrane spanning 4-domains A2
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000149534
Ensembl biotype	protein_coding
OMIM	147138
Entrez	2206

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000278888, ENST00000440896, ENST00000524868, ENST00000617306

RefSeq mRNA: 2 — MANE Select: NM_000139 NM_000139, NM_001256916

CCDS: CCDS73292, CCDS7980

Canonical transcript exons

ENST00000278888 — 7 exons

Exon	Start	End
ENSE00000991107	60093400	60093558
ENSE00000991109	60093964	60094062
ENSE00001107716	60095558	60098467
ENSE00003567386	60090336	60090470
ENSE00003576016	60089692	60089821
ENSE00003590662	60092792	60092848
ENSE00003628046	60088664	60088821

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 84.21.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 9.2450 / max 3503.5752, expressed in 112 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114434	8.4250	104
114431	0.4332	23
114430	0.2667	19
114432	0.0641	11
114435	0.0320	11
114433	0.0240	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.21	gold quality
gall bladder	UBERON:0002110	83.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.69	gold quality
rectum	UBERON:0001052	77.25	gold quality
monocyte	CL:0000576	74.26	gold quality
right coronary artery	UBERON:0001625	74.06	gold quality
mononuclear cell	CL:0000842	74.03	gold quality
leukocyte	CL:0000738	72.89	gold quality
mucosa of stomach	UBERON:0001199	72.81	gold quality
smooth muscle tissue	UBERON:0001135	72.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.33	gold quality
lower esophagus	UBERON:0013473	71.27	gold quality
upper lobe of left lung	UBERON:0008952	71.07	gold quality
skin of hip	UBERON:0001554	70.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.58	gold quality
upper lobe of lung	UBERON:0008948	70.07	gold quality
mucosa of transverse colon	UBERON:0004991	69.86	gold quality
calcaneal tendon	UBERON:0003701	69.25	gold quality
right lung	UBERON:0002167	68.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	68.29	gold quality
skin of leg	UBERON:0001511	67.87	gold quality
vermiform appendix	UBERON:0001154	67.78	gold quality
esophagus	UBERON:0001043	67.71	gold quality
body of stomach	UBERON:0001161	67.37	gold quality
colonic epithelium	UBERON:0000397	67.33	gold quality
lung	UBERON:0002048	66.65	gold quality
zone of skin	UBERON:0000014	66.23	gold quality
skin of abdomen	UBERON:0001416	66.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.73	gold quality
small intestine	UBERON:0002108	65.40	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	2382.68
E-GEOD-130148	yes	1894.53
E-MTAB-8410	yes	1846.06
E-MTAB-6653	yes	1800.57
E-HCAD-15	yes	1661.65
E-MTAB-8322	yes	1616.73
E-HCAD-36	yes	1310.77
E-CURD-46	yes	1208.65
E-CURD-122	yes	1139.12
E-CURD-88	yes	1052.80
E-MTAB-10432	yes	829.06
E-HCAD-38	yes	721.15
E-MTAB-8207	yes	248.57
E-HCAD-1	yes	52.94
E-MTAB-9067	yes	14.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA1, GATA2, POU2F1, SPI1

miRNA regulators (miRDB)

107 targeting MS4A2, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-557	99.96	70.01	1640

Literature-anchored findings (GeneRIF, showing 34)

• Gene expression profiling after stimulation via high-affinity Fcepsilon receptor I (FcepsilonRI), showed the transcriptional levels of several CC chemokines were markedly increased. (PMID:12393595)
• Products of the beta gene may control the level of surface expression, influencing susceptibility to allergies. (PMID:12753743)
• The data suggested that the Gly237Gly genotype of the Fc epsilon RI beta gene conferred genetic susceptibility to allergic asthma in Chinese, which affected the total plasma IgE levels in the allergic asthma patients. (PMID:12903039)
• A statistically significant association was foundbetween atopy and FcERIint2 variant polymorphism FcERIint2 polymorphism is related to atopy and may influence its development. (PMID:15087090)
• The genomic region encompassing the beta-chain has been linked to atopy and a number of polymorphisms within the FcepsilonRIbeta gene are associated with various atopic diseases. (PMID:15316148)
• FcepsilonRI beta-chain gene expression is down-regulated by a transcription factor, MZF-1, adn its cofactor FHL-3. (PMID:15453830)
• Single nucleotide polymorphisms (SNPs) in the Fc epsilon receptor I beta promoter are causally linked with atopy via regulation of Fc epsilon RI expression. (PMID:15528387)
• The speed of allergic symptom generation depends on the degree of IgE Fc epsilon receptor type I receptor triggering. (PMID:17088130)
• in the Korean general population, airway hyper-responsiveness is significantly associated with the E237G polymorphism of FcepsilonRI-beta, which results in an intolerant amino acid substitution (PMID:17430357)
• In caucasian, allergic patients, FCER1A and FCER1B polymorphisms showed an additive association with total serum IgE levels. (PMID:17686114)
• FcepsilonRIbeta E237G allele may have a protective role in wheezing illness among Taiwanese schoolchildren, depending on airway oxidative stress levels. (PMID:18269668)
• The -237T>G polymorphism may be associated with the rate of atopy, which in turn could increase the release of histamine from basophils and may lead to the development of the aspirin-intolerant chronic urticaria (PMID:18534082)
• PLSCR1 is a novel amplifier of FcepsilonRI signaling that acts selectively on the Lyn-initiated LAT/phospholipase Cgamma1/calcium axis, resulting in potentiation of a selected set of mast cell responses (PMID:18579528)
• Fcgr4 is a mouse IgE receptor that resembles macrophage MS4A2 protein in humans and promotes IgE-induced lung inflammation. (PMID:18949059)
• A promoter-dependent mechanism with altered transcriptional regulation of FcepsilonRIbeta may be involved for its association with asthma. (PMID:19218813)
• Polymorphisms in the Fc epsilon R1beta gene confer susceptibility to atopy in Korean children and may have a disease-modifying effect on airways in asthmatic patients. (PMID:19288130)
• Methylation levels at the AluSp repeat analysed in MS4A2 were inconsistent with classical imprinting mechanisms and did not associate with atopy status (PMID:19796196)
• No associations with total and specific IgE levels as well as allergic sensitization were seen for FCER1B and FCER1G (PMID:20028371)
• Significant associations of single nucleotide polymorphisms with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9). Variants in IL4R and TLR4 were also related to allergen-specific IgE, but not for MS4A2 and TLR9. (PMID:20085599)
• Demethylation of specific regulatory elements within the FCER1G locus contributes to FcepsilonRI overexpression on monocytes from patients with atopic dermatitis. (PMID:22150093)
• The interaction between Lyn and FcepsilonRIbeta is indispensable for FcepsilonRI-mediated human mast cell activation. (PMID:22845063)
• t-FcepsilonRIbeta mediates Ca2+ -dependent microtubule formation, which promotes degranulation and cytokine release. (PMID:23643722)
• Cytoplasmic FcepsilonRIbeta, which is not co-localized with FcepsilonRIalpha, may function as a negative regulator, as it can capture important signalling molecules such as Lyn. (PMID:24118172)
• Data indicated that the MS4A2 gene E237G variant may be a risk factor for developing atopic asthma and the promoter -109T allele is a potential risk factor of asthma in Asians. (PMID:24495860)
• no association between gene polymorphism and chronic spontaneous urticaria in Kashmiri population (PMID:24953255)
• study found a difference in the frequencies of genotypes of FcvarepsilonRIbeta subunit int 2 in allergic rhinitis patients and controls. The FcvarepsilonRIbeta subunit int 2 gene polymorphism was found to be associated with allergic rhinitis in the Polish cohort (PMID:24981302)
• FcepsilonRIbeta -109C/T and IFN-gamma 874T/A polymorphisms may be influencing factors for asthma in the Asian population (PMID:25530133)
• The results explain how initial membrane interactions of clustered IgE-Fcepsilon RI complexes lead to downstream cellular responses. (PMID:25658351)
• in patients with allergic rhinitis without asthma, the FCER1B rs569108 and rs512555 polymorphisms are associated with increased risk of developing allergic rhinitis and with lower IgE levels. (PMID:26792385)
• MS4A2 was differentially expressed between Fibromyalgia patients and healthy controls. (PMID:27157394)
• Using immunohistochemistry, we validated that MS4A2, the beta subunit of the IgE receptor expressed on mast cells, is a favorable prognostic indicator and show that MS4A2 gene expression is an independent prognostic marker for early-stage lung cancer patient survival. (PMID:28775209)
• Interaction between antibiotic use and MS4A2 gene polymorphism on childhood eczema: a prospective birth cohort study. (PMID:34261469)
• Identification of redundancy between human FcepsilonRIbeta and MS4A6A proteins points toward additional complex mechanisms for FcepsilonRI trafficking and signaling. (PMID:36424895)
• Evaluation value and mechanism of ADRB2 and FCER1B gene polymorphisms in preterm infants with congenital respiratory diseases. (PMID:38158688)

Cross-species orthologs

26 orthologs

Organism	Symbol	Gene ID
danio_rerio	ms4a17a.6	ENSDARG00000007018
danio_rerio	ms4a17a.4	ENSDARG00000014024
danio_rerio	si:dkey-77f5.10	ENSDARG00000020548
danio_rerio	zgc:113425	ENSDARG00000026616
danio_rerio	ms4a17c.2	ENSDARG00000028659
danio_rerio	ms4a17a.7	ENSDARG00000043796
danio_rerio	ms4a17a.1	ENSDARG00000043798
danio_rerio	ms4a17a.8	ENSDARG00000043802
danio_rerio	ms4a17a.12	ENSDARG00000053563
danio_rerio	ms4a17a.16	ENSDARG00000054898
danio_rerio	si:dkey-7j14.6	ENSDARG00000090552
danio_rerio	ms4a17a.3	ENSDARG00000091970
danio_rerio	ms4a17a.5	ENSDARG00000092204
danio_rerio	si:dkey-174k12.3	ENSDARG00000092593
danio_rerio	si:dkey-238j22.1	ENSDARG00000093512
danio_rerio	si:ch73-56d11.5	ENSDARG00000093546
danio_rerio	ms4a17c.1	ENSDARG00000094643
danio_rerio	ms4a17a.11	ENSDARG00000094809
danio_rerio	ms4a17a.9	ENSDARG00000094854
danio_rerio	ms4a17a.10	ENSDARG00000095695
danio_rerio	si:ch73-56d11.3	ENSDARG00000097527
danio_rerio	tmem176l.3a	ENSDARG00000098387
danio_rerio	ms4a17a.2	ENSDARG00000105674
danio_rerio	ms4a17a.17	ENSDARG00000116378
mus_musculus	Ms4a2	ENSMUSG00000024680
rattus_norvegicus	Ms4a2	ENSRNOG00000020993

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), MS4A7 (ENSG00000166927), MS4A14 (ENSG00000166928), MS4A5 (ENSG00000166930), MS4A8 (ENSG00000166959), MS4A15 (ENSG00000166961), MS4A10 (ENSG00000172689), TMEM212 (ENSG00000186329), MS4A13 (ENSG00000204979), MS4A18 (ENSG00000214782), MS4A4E (ENSG00000214787)

Protein

Protein identifiers

High affinity immunoglobulin epsilon receptor subunit beta — Q01362 (reviewed: Q01362)

Alternative names: Fc epsilon receptor I beta-chain, IgE Fc receptor subunit beta, Membrane-spanning 4-domains subfamily A member 2

All UniProt accessions (3): Q01362, A0A0B4J2E9, E9PLJ1

UniProt curated annotations — full annotation on UniProt →

Function. High affinity receptor that binds to the Fc region of immunoglobulins epsilon. Aggregation of FCER1 by multivalent antigens is required for the full mast cell response, including the release of preformed mediators (such as histamine) by degranulation and de novo production of lipid mediators and cytokines. Also mediates the secretion of important lymphokines. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators responsible for the manifestations of allergy.

Subunit / interactions. Tetramer of an alpha chain, a beta chain, and two disulfide linked gamma chains. Binds LILRB1. Interacts with FGR, FES/FPS and LYN.

Subcellular location. Membrane.

Tissue specificity. Found on the surface of mast cells and basophils.

Post-translational modifications. Phosphorylated on tyrosine residues by LYN.

Polymorphism. Variant Glu-237 has been found to be present in about 5.3% of a 1004 individuals population sample in Australia.

Similarity. Belongs to the MS4A family.

RefSeq proteins (2): NP_000130, NP_001243845 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030417	MS4A	Family

Pfam: PF04103

UniProt features (25 total): topological domain 5, helix 5, modified residue 4, transmembrane region 4, sequence variant 3, turn 3, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8YWA	ELECTRON MICROSCOPY	3.14
8YVU	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01362-F1	74.56	0.34

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 (4): 219, 225, 226, 229

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-2871809	FCERI mediated Ca+2 mobilization
R-HSA-2871837	FCERI mediated NF-kB activation

MSigDB gene sets: 101 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_64, GOCC_CELL_SURFACE, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, MODULE_75, MODULE_289, MODULE_99, MODULE_123, KEGG_ASTHMA, MODULE_46, GATA_Q6, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_GRANULOCYTE_DN, GOCC_SIDE_OF_MEMBRANE, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_PLASMA_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (3): immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), signal transduction (GO:0007165)

GO Molecular Function (2): IgE binding (GO:0019863), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), Fc-epsilon receptor I complex (GO:0032998), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Fc epsilon receptor (FCERI) signaling	4
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	1
response to stimulus	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
immunoglobulin binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
Fc receptor complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A2	FCER1A	P12319	927
MS4A2	FCER1G	P30273	858
MS4A2	MS4A5	Q9H3V2	858
MS4A2	COL6A5	A8TX70	767
MS4A2	CMA1	P23946	740
MS4A2	CPA3	P15088	711
MS4A2	TCN1	P20061	676
MS4A2	CD3D	P04234	668
MS4A2	PHF11	Q9UIL8	663
MS4A2	SART1	O43290	639
MS4A2	SPINK5	Q9NQ38	635
MS4A2	SLC45A3	Q96JT2	634
MS4A2	CD79A	P11912	627
MS4A2	NKG7	Q16617	622
MS4A2	BANK1	Q8NDB2	609

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MS4A2	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	MS4A2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): MS4A2 (Affinity Capture-Western), TMEM86A (Two-hybrid), MS4A2 (Reconstituted Complex), MS4A2 (Affinity Capture-Western), MS4A2 (Two-hybrid), MS4A2 (Co-fractionation), APP (Reconstituted Complex)

ESM2 similar proteins: A4IIU3, A6NML5, D3YWQ9, O75204, P0DP42, P11836, P20490, P56749, Q01362, Q0IIL2, Q2KJ11, Q2YDM3, Q32KQ5, Q3T110, Q3YBM2, Q497B3, Q4G068, Q504G0, Q5EB63, Q5FWC3, Q5HYL7, Q5M962, Q5R8D6, Q5R9K1, Q5RCD5, Q5RFC1, Q6GV28, Q7T392, Q7TQI0, Q7YQI4, Q8BGP5, Q8BHH8, Q8C6V3, Q8K177, Q8NCR9, Q8VHW1, Q8WXS4, Q920C4, Q925D4, Q940P5

Diamond homologs: A6QPF4, P11836, P13386, P19437, P20490, Q01362, Q3C1V0, Q3C2E2, Q3UPL6, Q8N5U1, Q920C4, Q96JA4, Q96JQ5, Q99N05, Q99N07, Q99N09, Q99N10, Q9BY19, Q9H2W1, Q9H3V2, Q9NXJ0, Q96HJ5, Q99N08, Q5REZ6, Q96PG2, Q9GZW8, Q96PG1, Q96DS6, Q2YDM3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MS4A2	“form complex”	FCER1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

858 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60088820:AGGTA:A	donor_loss	1.0000
11:60088823:T:G	donor_loss	1.0000
11:60089688:ACAGT:A	acceptor_gain	1.0000
11:60089689:C:G	acceptor_gain	1.0000
11:60089690:A:AG	acceptor_gain	1.0000
11:60089690:AGT:A	acceptor_gain	1.0000
11:60089691:G:GA	acceptor_gain	1.0000
11:60089691:GT:G	acceptor_gain	1.0000
11:60089691:GTG:G	acceptor_gain	1.0000
11:60089691:GTGT:G	acceptor_gain	1.0000
11:60089820:GG:G	donor_gain	1.0000
11:60089821:GG:G	donor_gain	1.0000
11:60089822:G:GA	donor_loss	1.0000
11:60089823:T:A	donor_loss	1.0000
11:60089824:G:GT	donor_loss	1.0000
11:60092790:A:AG	acceptor_gain	1.0000
11:60092791:G:GG	acceptor_gain	1.0000
11:60088822:G:GG	donor_gain	0.9900
11:60089688:A:AG	acceptor_gain	0.9900
11:60089690:A:C	acceptor_loss	0.9900
11:60089690:AGTGT:A	acceptor_gain	0.9900
11:60089691:G:GT	acceptor_loss	0.9900
11:60089691:GTGTG:G	acceptor_gain	0.9900
11:60089818:GGGG:G	donor_gain	0.9900
11:60089819:GGG:G	donor_gain	0.9900
11:60089819:GGGG:G	donor_gain	0.9900
11:60089820:GGG:G	donor_gain	0.9900
11:60089822:G:GG	donor_gain	0.9900
11:60089825:A:AT	donor_loss	0.9900
11:60090471:G:GG	donor_gain	0.9900

AlphaMissense

1579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60093430:A:C	S137R	0.985
11:60093432:C:A	S137R	0.985
11:60093432:C:G	S137R	0.985
11:60093433:A:C	S138R	0.973
11:60093435:C:A	S138R	0.973
11:60093435:C:G	S138R	0.973
11:60090447:T:G	Y100D	0.957
11:60093474:C:A	N151K	0.957
11:60093474:C:G	N151K	0.957
11:60090456:T:A	W103R	0.949
11:60090456:T:C	W103R	0.949
11:60094009:A:C	S195R	0.945
11:60094011:T:A	S195R	0.945
11:60094011:T:G	S195R	0.945
11:60093476:T:C	L152P	0.934
11:60090459:G:A	G104R	0.929
11:60090459:G:C	G104R	0.929
11:60093451:G:A	G144R	0.928
11:60093451:G:C	G144R	0.928
11:60093440:C:A	A140D	0.927
11:60090363:T:C	C72R	0.926
11:60090435:T:C	F96L	0.926
11:60090437:T:A	F96L	0.926
11:60090437:T:G	F96L	0.926
11:60089813:T:C	F60L	0.923
11:60089815:C:A	F60L	0.923
11:60089815:C:G	F60L	0.923
11:60093452:G:A	G144E	0.922
11:60092792:T:C	F108L	0.920
11:60092794:T:A	F108L	0.920

dbSNP variants (sampled 300 via entrez): RS1000419687 (11:60090382 T>C), RS1000591240 (11:60095133 A>G), RS1000875220 (11:60090736 G>C,T), RS1000928244 (11:60098478 G>A), RS1001007831 (11:60095401 G>A,C,T), RS1001130852 (11:60096602 G>T), RS1001218430 (11:60091539 G>A), RS1001255830 (11:60089852 G>C), RS1001458681 (11:60097940 G>A,T), RS1001886812 (11:60098182 C>T), RS1002100885 (11:60095028 A>T), RS1003253172 (11:60087052 A>G), RS1003332755 (11:60088384 T>A), RS1003597635 (11:60090119 C>A,T), RS1003719715 (11:60093321 C>G,T)

Disease associations

OMIM: gene MIM:147138 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
IgE responsiveness, atopic	No Known Disease Relationship	Unknown

Mondo (1): IgE responsiveness, atopic (MONDO:0007817)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009019_2	Alzheimer’s disease	5.000000e-08
GCST009021_5	Alzheimer’s disease	9.000000e-13

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564133	Ige Responsiveness, Atopic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs569108	MS4A2		0.00	0
rs12361312	MS4A2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Fc epsilon receptors

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aspirin	affects response to substance	3
Ozone	affects expression, increases abundance, affects reaction, affects response to substance	2
fulvic acid	affects cotreatment, decreases reaction, increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases reaction, affects expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
CGP 52608	affects binding, increases reaction	1
clothianidin	decreases expression	1
Calcimycin	increases expression, affects cotreatment, decreases reaction	1
Air Pollutants	increases abundance, affects expression	1
Benzo(a)pyrene	increases methylation	1
Latex	decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Methotrexate	increases expression	1
Nickel	affects expression, decreases reaction	1
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression	1
Aflatoxin B1	increases methylation	1
beta-Lactams	affects response to substance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C4MP	RBL SX-38	Cancer cell line
CVCL_SY86	HAP1 MS4A2 (-) 1	Cancer cell line	Male
CVCL_SY87	HAP1 MS4A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414141	PHASE3	COMPLETED	Efficacy and Safety/Tolerability of Grass MATA MPL
NCT00423787	PHASE3	COMPLETED	Efficacy and Safety/Tolerability of Ragweed MATA MPL
NCT00104377	PHASE2	COMPLETED	Induction of Immunogenicity With Different Doses of Grass MATA in Subjects Allergic to Grass and Rye Pollen
NCT00110786	PHASE2	COMPLETED	Investigation of Efficacy and Safety of Ragweed MATAMPL, Pollinex-R and Placebo in Patients With Ragweed Allergy
NCT00113750	PHASE2	COMPLETED	Induction of Immunogenicity With Different Doses of TreeMATA in Subjects Allergic to Tree Pollen
NCT00118612	PHASE2	COMPLETED	Different Doses of Tyrosine Adsorbed Tree Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Tree Pollen
NCT00118625	PHASE2	COMPLETED	Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Tree Pollen Allergy Vaccine
NCT00133146	PHASE2	COMPLETED	Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Grass Pollen Allergy Vaccine
NCT00133159	PHASE2	COMPLETED	Different Doses of Tyrosine Adsorbed Grass Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Grass Pollen
NCT00258635	PHASE2	COMPLETED	Investigation of Safety+Efficacy of Different Doses of RagweedMATAMPL;Assessment of Residual Allergenicity Using Skin Prick Test
NCT00325338	PHASE2	COMPLETED	Follow-up Investigation of Efficacy of Ragweed MATAMPL,and Placebo in Patients With Ragweed-induced Seasonal Allergic Rhinitis
NCT00387478	PHASE2	TERMINATED	Investigation of Efficacy and Safety of Tree MATAMPL,Tree MATA, and Placebo in Patients With Birch-Induced Seasonal Allergic Rhinitis
NCT00461097	PHASE2	COMPLETED	Oral Immunotherapy for Childhood Egg Allergy
NCT00104390	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Grass/Rye Pollen Allergoid Using Skin Prick Testing
NCT00107705	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Tree (Birch, Hazel, and Alder) Pollen Allergoid Using Skin Prick Testing
NCT00109759	PHASE1	WITHDRAWN	Evaluation of Safety and Tolerability of Tyrosine Adsorbed Ragweed Pollen Allergoid With MPL (Monophosphoryl Lipid A)
NCT00116285	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Ragweed Pollen Allergoid With Monophosphoryl Lipid A (MPL) Using Skin Prick Testing
NCT00241410	PHASE1	COMPLETED	Safety, Immunological Effect and Efficacy of the Combined Application of MPL and Grass Pollen Allergen
NCT00850668	PHASE1	COMPLETED	Peanut Allergy Vaccine Study in Healthy and Peanut-allergic Adults
NCT00580606	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial
NCT01084174	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual/Oral Immunotherapy for the Treatment of Peanut Allergy
NCT05003804	PHASE1/PHASE2	COMPLETED	Allergic Disease Onset Prevention Study
NCT01407640	Not specified	COMPLETED	Diagnosis and Physiopathology of Insulin Allergy
NCT02561390	Not specified	COMPLETED	Comparison Between spIgE and Skin Prick Test of Local and Imported Aeroallergens
NCT02561429	Not specified	COMPLETED	Comparison of Difference Histamine Concentration (1, 5 and 10 mg/ml) for Skin Prick Test Positive Control
NCT02733926	Not specified	UNKNOWN	Effect of Vegetation in Kindergartens on the Immune Response of Children
NCT06065137	Not specified	COMPLETED	Standardised Drug Provocation Testing in Perioperative Hypersensitivity