MS4A7

Summary

MS4A7 (membrane spanning 4-domains A7, HGNC:13378) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 7 (Q9GZW8). 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 which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed.

Source: NCBI Gene 58475 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_021201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13378
Approved symbol	MS4A7
Name	membrane spanning 4-domains A7
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	CD20L4, CFFM4, MS4A8
Ensembl gene	ENSG00000166927
Ensembl biotype	protein_coding
OMIM	606502
Entrez	58475

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 5 retained_intron

ENST00000300184, ENST00000358246, ENST00000528215, ENST00000528500, ENST00000528587, ENST00000528808, ENST00000530027, ENST00000530234, ENST00000530614, ENST00000533849, ENST00000534016, ENST00000534310, ENST00000899565, ENST00000899566, ENST00000899567, ENST00000899568, ENST00000899569, ENST00000899570, ENST00000899571, ENST00000899572, ENST00000899573, ENST00000899574, ENST00000899575, ENST00000971160, ENST00000971161, ENST00000971162, ENST00000971163

RefSeq mRNA: 4 — MANE Select: NM_021201 NM_021201, NM_206938, NM_206939, NM_206940

CCDS: CCDS7985, CCDS7986

Canonical transcript exons

ENST00000300184 — 7 exons

Exon	Start	End
ENSE00001107869	60385088	60385222
ENSE00002164504	60393787	60395948
ENSE00002195954	60378532	60378664
ENSE00003505427	60383129	60383288
ENSE00003613164	60386717	60386773
ENSE00003668006	60392685	60392786
ENSE00003686330	60389390	60389596

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 98.42.

FANTOM5 (CAGE): breadth broad, TPM avg 25.6287 / max 1510.6668, expressed in 466 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114459	25.6287	466
114458	1.5822	273
114457	1.5207	270
114460	1.2884	283
114461	0.7842	191
114462	0.3404	80
114463	0.0581	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.42	gold quality
leukocyte	CL:0000738	98.21	gold quality
spleen	UBERON:0002106	98.17	gold quality
gall bladder	UBERON:0002110	97.13	gold quality
vermiform appendix	UBERON:0001154	96.64	gold quality
upper lobe of left lung	UBERON:0008952	94.84	gold quality
upper lobe of lung	UBERON:0008948	94.50	gold quality
granulocyte	CL:0000094	94.47	gold quality
right lung	UBERON:0002167	94.47	gold quality
rectum	UBERON:0001052	94.28	gold quality
trabecular bone tissue	UBERON:0002483	94.17	gold quality
lower lobe of lung	UBERON:0008949	92.41	gold quality
right adrenal gland cortex	UBERON:0035827	91.75	gold quality
right coronary artery	UBERON:0001625	91.47	gold quality
smooth muscle tissue	UBERON:0001135	91.25	gold quality
lung	UBERON:0002048	90.99	gold quality
left adrenal gland cortex	UBERON:0035825	90.92	gold quality
blood	UBERON:0000178	90.62	gold quality
left adrenal gland	UBERON:0001234	90.47	gold quality
omental fat pad	UBERON:0010414	90.28	gold quality
peritoneum	UBERON:0002358	90.19	gold quality
right adrenal gland	UBERON:0001233	89.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.17	gold quality
descending thoracic aorta	UBERON:0002345	89.14	gold quality
adrenal cortex	UBERON:0001235	89.13	gold quality
mucosa of stomach	UBERON:0001199	88.83	gold quality
adrenal gland	UBERON:0002369	88.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.24	gold quality
calcaneal tendon	UBERON:0003701	88.19	gold quality
bone marrow cell	CL:0002092	87.60	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	2543.94
E-CURD-122	yes	2248.67
E-MTAB-7407	yes	2224.18
E-CURD-55	yes	1445.08
E-MTAB-6653	yes	1222.95
E-MTAB-8207	yes	1124.84
E-MTAB-9221	yes	945.59
E-GEOD-149689	yes	905.07
E-HCAD-32	yes	792.95
E-CURD-112	yes	759.15
E-ENAD-20	yes	192.32
E-HCAD-1	yes	102.68
E-MTAB-6701	yes	89.38
E-HCAD-4	yes	75.41
E-GEOD-135922	yes	61.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting MS4A7, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 2)

• The short isoform of MS4A7 is a novel player in glioblastoma microenvironment, M2 macrophage polarization, and tumor progression. (PMID:36944954)
• Hepatic danger signaling triggers TREM2[+] macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation. (PMID:38478630)

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	Ms4a7	ENSMUSG00000024672
rattus_norvegicus	Ms4a7	ENSRNOG00000020953

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), 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 7 — Q9GZW8 (reviewed: Q9GZW8)

Alternative names: CD20 antigen-like 4, CD20/FC-epsilon-RI-beta family member 4, Four-span transmembrane protein 2

All UniProt accessions (5): Q9GZW8, E9PIV6, E9PL98, E9PM26, E9PN40

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. Ubiquitous expression in normal tissues. Expression is more elevated in adult liver, lung, spleen, and heart than in their fetal counterparts, and is higher in normal tissues than in the cancerous tissue or cell lines. Low levels of expression were detected in the promonocytic stage, whereas high levels of expression were detected in mature monocytes.

Similarity. Belongs to the MS4A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZW8-1	1	yes
Q9GZW8-2	2

RefSeq proteins (4): NP_067024, NP_996821, NP_996822, NP_996823 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030417	MS4A	Family

Pfam: PF04103

UniProt features (15 total): topological domain 5, transmembrane region 4, sequence variant 3, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZW8-F1	74.77	0.33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 219 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_TRANS_GOLGI_NETWORK, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, OCT1_03, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, VANTVEER_BREAST_CANCER_POOR_PROGNOSIS, SABATES_COLORECTAL_ADENOMA_DN, ACEVEDO_LIVER_CANCER_UP, LIAN_LIPA_TARGETS_3M, ZHENG_BOUND_BY_FOXP3, GOCC_ORGANELLE_SUBCOMPARTMENT, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_METABOLIC_SYNDROM_NETWORK, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP

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

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A7	MS4A1	P08984	785
MS4A7	CCDC180	Q9P1Z9	369
MS4A7	MS4A3	Q96HJ5	360
MS4A7	KRTAP11-1	Q8IUC1	355
MS4A7	MS4A18	Q3C1V0	349
MS4A7	HEPHL1	Q6MZM0	337
MS4A7	ZNF704	Q6ZNC4	322
MS4A7	BLID	Q8IZY5	305
MS4A7	CACNG5	Q9UF02	305
MS4A7	CPNE4	Q96A23	292
MS4A7	HEXB	P07686	290
MS4A7	ZNF154	Q13106	287
MS4A7	CSF2RB	P32927	284
MS4A7	CDKL2	Q92772	277
MS4A7	RIT2	Q99578	262

IntAct

30 interactions, top by confidence:

A	B	Type	Score
EMP1	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
CD72	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
PLN	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
LAT	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
PMP22	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
DRAM1	MS4A7	psi-mi:“MI:0915”(physical association)	0.560
MS4A7	CPNE7	psi-mi:“MI:0915”(physical association)	0.400
CD72	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
IGFBP5	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
ITGB2	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
PLN	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
LAT	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
PMP22	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
DRAM1	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
chaA	MS4A7	psi-mi:“MI:0915”(physical association)	0.000
MS4A7	SLC35F6	psi-mi:“MI:0915”(physical association)	0.000
MS4A7	HMGCL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): CPNE7 (Affinity Capture-MS), SLC35F6 (Two-hybrid), HMGCL (Two-hybrid), MS4A7 (Two-hybrid), MS4A7 (Two-hybrid), MS4A7 (Two-hybrid), MS4A7 (Two-hybrid), MS4A7 (Two-hybrid), MS4A7 (Two-hybrid), PLN (Two-hybrid), LAT (Two-hybrid), CPNE7 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8RY99, A4IIV4, A8MUP6, A9UL59, B2RVW2, C9JDP6, E9Q6I0, H7C241, O95859, P0DP42, P56749, Q0IIL2, Q0V9E0, Q29RH7, Q2KHT4, Q32KQ5, Q3SZT1, Q3T110, Q3UUA0, Q4V922, Q5CZV0, Q5FWC3, Q5J8X5, Q5R8B5, Q5R9K1, Q6AXT9, Q6AYL2, Q6GV27, Q6GV28, Q6ICI0, Q7T392, Q80SV1, Q80WE5, Q86WI0, Q8CJ58, Q8K445, Q8NHS1, Q8R1W2, Q8VI88, Q96CE8

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1147 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60699771:GCAAG:G	donor_gain	1.0000
11:60715130:GCAAT:G	donor_gain	1.0000
11:60699773:AAGG:A	donor_loss	0.9900
11:60699774:AGGTG:A	donor_loss	0.9900
11:60699775:GGTG:G	donor_loss	0.9900
11:60699776:G:GG	donor_gain	0.9900
11:60699776:GT:G	donor_loss	0.9900
11:60708722:GATC:G	donor_gain	0.9900
11:60708725:C:CG	donor_gain	0.9900
11:60708725:C:G	donor_gain	0.9900
11:60714536:A:G	donor_gain	0.9900
11:60714556:G:GT	donor_gain	0.9900
11:60714556:G:T	donor_gain	0.9900
11:60715135:G:GG	donor_gain	0.9900
11:60715304:TTCCA:T	acceptor_loss	0.9900
11:60715305:TCCA:T	acceptor_loss	0.9900
11:60715307:CA:C	acceptor_loss	0.9900
11:60715309:GGTGA:G	acceptor_gain	0.9900
11:60699774:AG:A	donor_gain	0.9800
11:60699775:GG:G	donor_gain	0.9800
11:60701076:GGGG:G	donor_gain	0.9800
11:60701077:GGGG:G	donor_gain	0.9800
11:60708649:GCT:G	acceptor_gain	0.9800
11:60714576:G:GT	donor_gain	0.9800
11:60715132:AATG:A	donor_loss	0.9800
11:60715133:AT:A	donor_gain	0.9800
11:60715133:ATGTG:A	donor_loss	0.9800
11:60715134:TGTG:T	donor_loss	0.9800
11:60715136:TGAGT:T	donor_loss	0.9800
11:60715137:G:GG	donor_loss	0.9800

AlphaMissense

1535 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60389420:A:C	S124R	0.986
11:60389422:T:A	S124R	0.986
11:60389422:T:G	S124R	0.986
11:60386717:T:C	F95L	0.974
11:60386719:T:A	F95L	0.974
11:60386719:T:G	F95L	0.974
11:60385121:A:C	S61R	0.971
11:60385123:T:A	S61R	0.971
11:60385123:T:G	S61R	0.971
11:60389432:G:C	A128P	0.940
11:60385106:T:C	C56R	0.934
11:60389433:C:A	A128E	0.927
11:60385220:T:C	C94R	0.924
11:60385103:T:C	C55R	0.922
11:60385199:T:G	Y87D	0.914
11:60392723:G:C	E195D	0.908
11:60392723:G:T	E195D	0.908
11:60389442:G:A	G131D	0.896
11:60385127:G:A	G63R	0.894
11:60385127:G:C	G63R	0.894
11:60386730:G:A	G99E	0.894
11:60383286:G:T	G49W	0.893
11:60389441:G:C	G131R	0.882
11:60389421:G:A	S124N	0.879
11:60383286:G:A	G49R	0.878
11:60383286:G:C	G49R	0.878
11:60385211:G:A	G91R	0.875
11:60385211:G:C	G91R	0.875
11:60389413:T:A	N121K	0.870
11:60389413:T:G	N121K	0.870

dbSNP variants (sampled 300 via entrez): RS1000020281 (11:60387519 C>G), RS1000292754 (11:60381529 A>G), RS1000507269 (11:60394437 T>C), RS1000827299 (11:60395049 A>G), RS1000866317 (11:60386536 T>C), RS1000981056 (11:60392267 A>G), RS1001111197 (11:60395267 G>A), RS1001111852 (11:60392736 G>A), RS1001201696 (11:60387610 G>A), RS1001364410 (11:60393615 T>C), RS1001408895 (11:60380782 G>A), RS1001641256 (11:60387294 T>A), RS1001798989 (11:60380806 G>A,C), RS1002240887 (11:60385825 T>A), RS1002329909 (11:60391805 G>C)

Disease associations

OMIM: gene MIM:606502 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	3
nickel sulfate	increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
propionaldehyde	increases expression	1
cyanoginosin LR	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Pioglitazone	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Allergens	decreases expression	1
Calcitriol	decreases expression	1
Demecolcine	increases expression	1
Dinitrochlorobenzene	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Eugenol	increases expression	1
Methyl Methanesulfonate	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_VD95	BJAB GFP-MS4A7	Cancer cell line	Female

Clinical trials (associated diseases)

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