MS4A6E

Summary

MS4A6E (membrane spanning 4-domains A6E, HGNC:14285) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 6E (Q96DS6). May be involved in signal transduction as a component of a multimeric receptor complex.

This gene encodes 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. The gene encoding this protein is localized to 11q12.3, among a cluster of family members.

Source: NCBI Gene 245802 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_139249

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14285
Approved symbol	MS4A6E
Name	membrane spanning 4-domains A6E
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166926
Ensembl biotype	protein_coding
OMIM	608402
Entrez	245802

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000300182, ENST00000530509, ENST00000532756, ENST00000684409, ENST00000969922

RefSeq mRNA: 1 — MANE Select: NM_139249 NM_139249

CCDS: CCDS7984

Canonical transcript exons

ENST00000684409 — 5 exons

Exon	Start	End
ENSE00001107846	60339866	60339964
ENSE00001107847	60337741	60337947
ENSE00003918550	60327255	60327408
ENSE00003919667	60334882	60335042
ENSE00003921061	60340776	60341341

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 96.67.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.67	gold quality
right testis	UBERON:0004534	96.35	gold quality
testis	UBERON:0000473	93.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.27	gold quality
sperm	CL:0000019	92.66	gold quality
adult organism	UBERON:0007023	87.37	gold quality
monocyte	CL:0000576	82.25	gold quality
leukocyte	CL:0000738	79.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.76	gold quality
spleen	UBERON:0002106	71.33	gold quality
smooth muscle tissue	UBERON:0001135	67.97	gold quality
rectum	UBERON:0001052	66.38	gold quality
vermiform appendix	UBERON:0001154	65.80	gold quality
tibialis anterior	UBERON:0001385	65.15	silver quality
subcutaneous adipose tissue	UBERON:0002190	64.43	gold quality
granulocyte	CL:0000094	63.58	gold quality
right coronary artery	UBERON:0001625	63.29	gold quality
caecum	UBERON:0001153	60.25	gold quality
lymph node	UBERON:0000029	59.49	gold quality
upper lobe of left lung	UBERON:0008952	58.73	gold quality
gall bladder	UBERON:0002110	58.49	gold quality
upper lobe of lung	UBERON:0008948	58.02	gold quality
adipose tissue	UBERON:0001013	57.23	gold quality
omental fat pad	UBERON:0010414	57.13	gold quality
peritoneum	UBERON:0002358	57.08	gold quality
left uterine tube	UBERON:0001303	56.74	gold quality
left adrenal gland	UBERON:0001234	56.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	56.36	gold quality
right lung	UBERON:0002167	56.26	gold quality
left adrenal gland cortex	UBERON:0035825	56.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	4.54
E-ANND-3	yes	4.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting MS4A6E, 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-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-6858-5P	96.05	64.59	1020

Literature-anchored findings (GeneRIF, showing 1)

• Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. (PMID:21460841)

Cross-species orthologs

31 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	Ms4a6b	ENSMUSG00000024677
mus_musculus	Ms4a6d	ENSMUSG00000024679
mus_musculus	Ms4a6c	ENSMUSG00000079419
rattus_norvegicus	Ms4a6a	ENSRNOG00000020991
rattus_norvegicus	Ms4a6bl1	ENSRNOG00000030689
rattus_norvegicus	Ms4a6b	ENSRNOG00000047349
rattus_norvegicus	Ms4a6bl1	ENSRNOG00000050395

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A7 (ENSG00000166927), MS4A14 (ENSG00000166928), MS4A5 (ENSG00000166930), MS4A8 (ENSG00000166959), MS4A15 (ENSG00000166961), MS4A10 (ENSG00000172689), TMEM212 (ENSG00000186329), MS4A13 (ENSG00000204979), MS4A18 (ENSG00000214782), MS4A4E (ENSG00000214787)

Protein

Protein identifiers

Membrane-spanning 4-domains subfamily A member 6E — Q96DS6 (reviewed: Q96DS6)

All UniProt accessions (3): Q96DS6, H0YD45, H0YEW2

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in signal transduction as a component of a multimeric receptor complex.

Subcellular location. Membrane.

Tissue specificity. Expressed by malignant and fetal tissue at very low levels.

Similarity. Belongs to the MS4A family.

RefSeq proteins (1): NP_640342* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain

Pfam: PF04103

UniProt features (9 total): topological domain 3, sequence variant 3, transmembrane region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DS6-F1	63.77	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): GOCC_TRANS_GOLGI_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, BOSCO_TH1_CYTOTOXIC_MODULE, MIR587, MIR586, MIR338_3P, MIR5004_5P, MIR1224_5P, DESCARTES_MAIN_FETAL_ANTIGEN_PRESENTING_CELLS, GOCC_GOLGI_APPARATUS_SUBCOMPARTMENT, chr11q12, GSE2770_TGFB_AND_IL4_ACT_VS_ACT_CD4_TCELL_2H_DN, GSE19198_6H_VS_24H_IL21_TREATED_TCELL_DN, GSE19198_CTRL_VS_IL21_TREATED_TCELL_6H_DN, GOCC_GOLGI_APPARATUS

GO Biological Process (1): cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	1
binding	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A6E	MS4A4E	Q96PG1	977
MS4A6E	MS4A4A	Q96JQ5	976
MS4A6E	MS4A10	Q96PG2	929
MS4A6E	MS4A12	Q9NXJ0	927
MS4A6E	MS4A8	Q9BY19	921
MS4A6E	ABCA7	Q8IZY2	720
MS4A6E	CD2AP	Q9Y5K6	718
MS4A6E	PICALM	Q13492	696
MS4A6E	EPHA1	P21709	669
MS4A6E	SORL1	Q92673	627
MS4A6E	BIN1	O00499	624
MS4A6E	CLU	P10909	610
MS4A6E	ZCWPW1	Q9H0M4	606
MS4A6E	CD33	P20138	594
MS4A6E	MS4A5	Q9H3V2	584

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GJB2	MS4A6E	psi-mi:“MI:0915”(physical association)	0.560
MS4A6E	UBE2J1	psi-mi:“MI:0915”(physical association)	0.560
MS4A6E	ATP11C	psi-mi:“MI:0914”(association)	0.350
MS4A6E	POF1B	psi-mi:“MI:0914”(association)	0.350
GJB2	MS4A6E	psi-mi:“MI:0915”(physical association)	0.000
UBE2J1	MS4A6E	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): MS4A6E (Two-hybrid), UBE2J1 (Two-hybrid), ATP11C (Affinity Capture-MS), CCDC167 (Affinity Capture-MS), EVPL (Affinity Capture-MS), CALML5 (Affinity Capture-MS), POF1B (Affinity Capture-MS)

ESM2 similar proteins: A4IIU3, A6NGA9, A6NML5, D3YWQ9, O75204, P0DP42, P11836, P13386, P19437, P20490, P56749, Q01362, Q0IIL2, Q2KHT4, Q32KQ5, Q3SZ72, Q3T110, Q3UNB8, Q3YBM2, Q497B3, Q4G068, Q504G0, Q5EB63, Q5FWC3, Q5HYL7, Q5R8D6, Q5R9K1, Q5RCD5, Q5REZ6, Q6AXT9, Q6GV27, Q7YQI4, Q8BGP5, Q8C6V3, Q8K177, Q8R1W2, Q8VHW1, Q8VI88, Q8WXS4, Q920C4

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1482 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60335023:C:T	donor_gain	1.0000
11:60335029:TCA:T	donor_gain	1.0000
11:60335035:T:G	donor_gain	1.0000
11:60335038:TTGGG:T	donor_loss	1.0000
11:60335040:GGG:G	donor_gain	1.0000
11:60335041:GGG:G	donor_gain	1.0000
11:60335042:GGTAA:G	donor_loss	1.0000
11:60337649:A:G	donor_gain	1.0000
11:60337944:GGCT:G	donor_gain	1.0000
11:60337945:GCTG:G	donor_gain	1.0000
11:60337948:G:GG	donor_gain	1.0000
11:60340774:A:AG	acceptor_gain	1.0000
11:60340775:G:GG	acceptor_gain	1.0000
11:60335041:GG:G	donor_gain	0.9900
11:60335042:GG:G	donor_gain	0.9900
11:60335044:T:A	donor_loss	0.9900
11:60337654:GGAA:G	donor_gain	0.9900
11:60337655:G:T	donor_gain	0.9900
11:60337735:TTTCA:T	acceptor_loss	0.9900
11:60337736:TTCA:T	acceptor_loss	0.9900
11:60337738:CAGGT:C	acceptor_loss	0.9900
11:60337739:A:G	acceptor_loss	0.9900
11:60337740:GGTGC:G	acceptor_gain	0.9900
11:60337845:GT:G	donor_gain	0.9900
11:60337943:TGGCT:T	donor_gain	0.9900
11:60337944:GGCTG:G	donor_gain	0.9900
11:60337945:GCT:G	donor_gain	0.9900
11:60337946:CT:C	donor_gain	0.9900
11:60337946:CTGTA:C	donor_loss	0.9900
11:60337947:TGTA:T	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000128694 (11:60345138 G>A,T), RS1000343296 (11:60339142 A>T), RS1000375136 (11:60325957 T>C), RS1000540893 (11:60329150 C>A,T), RS1000572082 (11:60328947 T>C), RS1000794216 (11:60338227 T>A), RS1000886783 (11:60331911 A>T), RS1001043330 (11:60344820 TCC>T), RS1001064818 (11:60343931 C>T), RS1001180140 (11:60345040 T>C), RS1001210413 (11:60344455 A>G), RS1001306358 (11:60344726 G>A), RS1001497019 (11:60325447 G>C,T), RS1001539996 (11:60343576 T>A,C), RS1001555925 (11:60332915 T>C)

Disease associations

OMIM: gene MIM:608402 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002817_25	Alzheimer’s disease in APOE e4- carriers	2.000000e-09
GCST003262_560	Post bronchodilator FEV1	3.000000e-06
GCST010058_1	Hematological and biochemical traits	1.000000e-06
GCST90002393_230	Monocyte count	8.000000e-24

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0007629	hemoglobin A1 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

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

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Arbutin	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Aflatoxin B1	decreases methylation	1
Nanotubes, Carbon	decreases expression	1

Clinical trials (associated diseases)

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