MS4A4E

Summary

MS4A4E (membrane spanning 4-domains A4E, HGNC:14284) is a protein-coding gene on chromosome 11q12.2, encoding Putative membrane-spanning 4-domains subfamily A member 4E (Q96PG1).

Most MS4A genes, including MS4A4E, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.

Source: NCBI Gene 643680 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• MANE Select transcript: NM_001393391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14284
Approved symbol	MS4A4E
Name	membrane spanning 4-domains A4E
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214787
Ensembl biotype	protein_coding
OMIM	608401
Entrez	643680

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 protein_coding

ENST00000398984, ENST00000425663, ENST00000526086, ENST00000526153, ENST00000528394, ENST00000532442, ENST00000638529, ENST00000651255

RefSeq mRNA: 2 — MANE Select: NM_001393391 NM_001351235, NM_001393391

CCDS: CCDS91480

Canonical transcript exons

ENST00000651255 — 9 exons

Exon	Start	End
ENSE00002462437	60242958	60243137
ENSE00003538889	60214571	60214614
ENSE00003635442	60229912	60230071
ENSE00003656769	60228594	60228627
ENSE00003715915	60208593	60208694
ENSE00003843334	60200270	60201879
ENSE00003844429	60205714	60205820
ENSE00003847001	60212974	60213132
ENSE00003851067	60204890	60204958

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 87.32.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3500 / max 297.3895, expressed in 217 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119908	1.2135	199
119905	0.0503	22
119906	0.0338	14
119907	0.0285	15
206296	0.0238	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	87.32	gold quality
leukocyte	CL:0000738	85.80	gold quality
calcaneal tendon	UBERON:0003701	81.28	gold quality
spleen	UBERON:0002106	79.80	gold quality
sural nerve	UBERON:0015488	79.49	gold quality
mucosa of stomach	UBERON:0001199	79.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.97	gold quality
right coronary artery	UBERON:0001625	77.59	gold quality
blood	UBERON:0000178	77.34	gold quality
bone marrow	UBERON:0002371	77.31	gold quality
small intestine	UBERON:0002108	77.13	gold quality
granulocyte	CL:0000094	77.04	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.95	gold quality
right adrenal gland cortex	UBERON:0035827	76.89	gold quality
adipose tissue	UBERON:0001013	75.56	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.80	gold quality
lower esophagus	UBERON:0013473	74.72	gold quality
bone marrow cell	CL:0002092	74.41	gold quality
intestine	UBERON:0000160	74.23	gold quality
right adrenal gland	UBERON:0001233	74.23	gold quality
omental fat pad	UBERON:0010414	73.95	gold quality
transverse colon	UBERON:0001157	73.83	gold quality
right lung	UBERON:0002167	73.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.62	gold quality
colon	UBERON:0001155	73.57	gold quality
smooth muscle tissue	UBERON:0001135	73.23	gold quality
urinary bladder	UBERON:0001255	73.21	gold quality
tibial nerve	UBERON:0001323	72.99	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	279.00
E-ANND-3	yes	12.30
E-MTAB-9801	yes	4.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• ABCA7 and the MS4A6A/MS4A4E gene cluster are new Alzheimer’s disease susceptibility loci. (PMID:21460840)
• We replicated the rs11136000 (CLU)- rs670139 (MS4A4E) interaction, demonstrated an association in APOE epsilon4 negative subjects, and reported evidence of a possible dominant effect for MS4A4E. (PMID:26449541)
• Addition of the minor allele for rs670139 (MS4A4E), rs9331896 (CLU), and rs12155159 (NME8) was nominally associated with change on the DWRT, DSST, and WFT, respectively, in whites. For rs670139 and rs9331896 the association was only significant in individuals bearing at least one APOE 4 allele in stratified analyses. (PMID:27781389)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ms4a4a	ENSMUSG00000101389
rattus_norvegicus	Ms4a4a	ENSRNOG00000050024

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), MS4A7 (ENSG00000166927), MS4A14 (ENSG00000166928), MS4A5 (ENSG00000166930), MS4A8 (ENSG00000166959), MS4A15 (ENSG00000166961), MS4A10 (ENSG00000172689), TMEM212 (ENSG00000186329), MS4A13 (ENSG00000204979), MS4A18 (ENSG00000214782)

Protein

Protein identifiers

Putative membrane-spanning 4-domains subfamily A member 4E — Q96PG1 (reviewed: Q96PG1)

All UniProt accessions (5): A0A1W2PRK6, A0A494C1L8, E9PKS5, Q96PG1, H0YEM0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the MS4A family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96PG1-1	1	yes
Q96PG1-2	2
Q96PG1-3	3

RefSeq proteins (2): NP_001338164, NP_001380320* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain

Pfam: PF04103

UniProt features (7 total): transmembrane region 2, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PG1-F1	61.59	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 13 (showing top): DESCARTES_MAIN_FETAL_MYELOID_CELLS, DESCARTES_FETAL_ADRENAL_MYELOID_CELLS, DESCARTES_FETAL_HEART_MYELOID_CELLS, DESCARTES_FETAL_INTESTINE_MYELOID_CELLS, DESCARTES_FETAL_KIDNEY_MYELOID_CELLS, DESCARTES_FETAL_LIVER_MYELOID_CELLS, DESCARTES_FETAL_LUNG_MYELOID_CELLS, DESCARTES_FETAL_MUSCLE_MYELOID_CELLS, DESCARTES_FETAL_PANCREAS_MYELOID_CELLS, DESCARTES_FETAL_SPLEEN_MYELOID_CELLS, DESCARTES_FETAL_STOMACH_MYELOID_CELLS, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN, chr11q12

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A4E	MS4A6A	Q9H2W1	982
MS4A4E	MS4A6E	Q96DS6	977
MS4A4E	MS4A10	Q96PG2	929
MS4A4E	MS4A12	Q9NXJ0	915
MS4A4E	ABCA7	Q8IZY2	823
MS4A4E	CLU	P10909	806
MS4A4E	CD33	P20138	796
MS4A4E	PICALM	Q13492	774
MS4A4E	CD2AP	Q9Y5K6	761
MS4A4E	MS4A8	Q9BY19	713
MS4A4E	BIN1	O00499	703
MS4A4E	EPHA1	P21709	670
MS4A4E	SORL1	Q92673	636
MS4A4E	ZCWPW1	Q9H0M4	622
MS4A4E	NME8	Q8N427	609

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GTR0, A0A1B0GVN3, A6H7F9, A6NFE2, A7TZG1, A7TZG3, A7XV04, A7XV14, B0ZE70, B1B212, B2RTN2, B3F0J0, D2HQI1, O97687, P01586, P06740, P16745, P22794, P40221, P40933, P48092, P48346, P97604, Q01151, Q28028, Q29RT9, Q3TB92, Q3Y5G8, Q4GZL1, Q4U0U2, Q5BK38, Q5DT36, Q5DT37, Q5RBQ2, Q5RFR2, Q5UKY4, Q5WQV8, Q62875, Q68D85, Q75SZ9

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1375 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60229907:CTTA:C	donor_loss	1.0000
11:60229908:TTACC:T	donor_loss	1.0000
11:60229909:TACCC:T	donor_loss	1.0000
11:60229910:AC:A	donor_gain	1.0000
11:60229910:ACC:A	donor_gain	1.0000
11:60229911:C:CT	donor_loss	1.0000
11:60229911:CC:C	donor_gain	1.0000
11:60229911:CCC:C	donor_gain	1.0000
11:60214615:C:CC	acceptor_gain	0.9900
11:60228510:T:TC	acceptor_gain	0.9900
11:60228730:C:G	acceptor_gain	0.9900
11:60229906:ACTT:A	donor_loss	0.9900
11:60229910:A:AC	donor_gain	0.9900
11:60229910:ACCC:A	donor_gain	0.9900
11:60229911:C:CC	donor_gain	0.9900
11:60229911:CCCC:C	donor_gain	0.9900
11:60229911:CCCCA:C	donor_gain	0.9900
11:60208412:C:CA	donor_gain	0.9800
11:60229905:GACTT:G	donor_loss	0.9800
11:60214613:TA:T	acceptor_gain	0.9700
11:60228729:TCTAG:T	acceptor_gain	0.9600
11:60228510:T:C	acceptor_gain	0.9500
11:60228727:CCT:C	acceptor_gain	0.9300
11:60228728:CTC:C	acceptor_gain	0.9300
11:60213001:A:AC	donor_gain	0.9100
11:60213208:TGTC:T	donor_gain	0.8800
11:60213211:C:CT	donor_gain	0.8700
11:60213212:T:TT	donor_gain	0.8700
11:60214610:GGATA:G	acceptor_gain	0.8600
11:60229929:T:TA	donor_gain	0.8400

AlphaMissense

2148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60229939:G:C	F39L	0.759
11:60229939:G:T	F39L	0.759
11:60229941:A:G	F39L	0.759

dbSNP variants (sampled 300 via entrez): RS1000048184 (11:60209558 T>C), RS1000059646 (11:60221081 A>G), RS1000074188 (11:60220812 G>A), RS1000263393 (11:60244014 G>A), RS1000268898 (11:60243781 A>G), RS1000301308 (11:60238358 ATTTTGTATTTCTTCTTAT>A), RS1000311277 (11:60231717 G>A), RS1000342008 (11:60231362 T>C), RS1000426054 (11:60210094 C>G,T), RS1000451143 (11:60203245 A>T), RS1000602314 (11:60225255 A>T), RS1000641004 (11:60237774 T>C), RS1000657272 (11:60230536 G>T), RS1000660038 (11:60231982 G>A), RS1000781056 (11:60203904 A>G)

Disease associations

OMIM: gene MIM:608401 | 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
GCST001025_2	Alzheimer’s disease	2.000000e-14
GCST001727_6	Lipoprotein-associated phospholipase A2 activity and mass	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement

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
benzo(e)pyrene	decreases methylation, increases methylation	1
2-palmitoylglycerol	increases expression	1
licochalcone B	increases expression	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	decreases methylation, increases methylation	1

Clinical trials (associated diseases)

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