MS4A15

Summary

MS4A15 (membrane spanning 4-domains A15, HGNC:28573) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 15 (Q8N5U1). May be involved in signal transduction as a component of a multimeric receptor complex.

Predicted to be involved in cell surface receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 219995 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_001098835

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28573
Approved symbol	MS4A15
Name	membrane spanning 4-domains A15
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166961
Ensembl biotype	protein_coding
Entrez	219995

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000337911, ENST00000405633, ENST00000429322, ENST00000528170, ENST00000871882, ENST00000871883, ENST00000871884, ENST00000871885, ENST00000871886, ENST00000871887

RefSeq mRNA: 3 — MANE Select: NM_001098835 NM_001098835, NM_001278242, NM_152717

CCDS: CCDS44617, CCDS60802, CCDS7991

Canonical transcript exons

ENST00000405633 — 7 exons

Exon	Start	End
ENSE00001719326	60767533	60767655
ENSE00002174122	60756867	60757058
ENSE00002283877	60763706	60763958
ENSE00003558665	60771291	60771347
ENSE00003658577	60773837	60773950
ENSE00003666793	60773392	60773484
ENSE00003894803	60775605	60776733

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 95.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0236 / max 19.7273, expressed in 7 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114493	0.0122	7
114494	0.0114	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	95.94	gold quality
upper lobe of left lung	UBERON:0008952	88.92	gold quality
upper lobe of lung	UBERON:0008948	87.79	gold quality
lung	UBERON:0002048	79.43	gold quality
lower lobe of lung	UBERON:0008949	77.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.05	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.14	gold quality
jejunal mucosa	UBERON:0000399	60.45	silver quality
adult organism	UBERON:0007023	54.71	silver quality
jejunum	UBERON:0002115	51.29	silver quality
duodenum	UBERON:0002114	49.60	gold quality
oocyte	CL:0000023	49.36	gold quality
skin of hip	UBERON:0001554	47.66	silver quality
placenta	UBERON:0001987	45.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
small intestine	UBERON:0002108	42.69	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
prefrontal cortex	UBERON:0000451	41.34	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
tonsil	UBERON:0002372	41.26	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.48
E-MTAB-6058	no	1.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting MS4A15, 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-10401-5P	99.99	65.79	948
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-4700-5P	98.63	67.43	1915

Literature-anchored findings (GeneRIF, showing 1)

• MS4A15 acts as an oncogene in ovarian cancer through reprogramming energy metabolism. (PMID:35151203)

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	Ms4a15	ENSMUSG00000067571
rattus_norvegicus	Ms4a15	ENSRNOG00000026957

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), MS4A7 (ENSG00000166927), MS4A14 (ENSG00000166928), MS4A5 (ENSG00000166930), MS4A8 (ENSG00000166959), MS4A10 (ENSG00000172689), TMEM212 (ENSG00000186329), MS4A13 (ENSG00000204979), MS4A18 (ENSG00000214782), MS4A4E (ENSG00000214787)

Protein

Protein identifiers

Membrane-spanning 4-domains subfamily A member 15 — Q8N5U1 (reviewed: Q8N5U1)

All UniProt accessions (2): Q8N5U1, E7ET34

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.

Similarity. Belongs to the MS4A family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N5U1-1	1	yes
Q8N5U1-2	2
Q8N5U1-3	3

RefSeq proteins (3): NP_001092305, NP_001265171, NP_689930 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030417	MS4A	Family

Pfam: PF04103

UniProt features (10 total): transmembrane region 4, splice variant 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5U1-F1	68.60	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): GOZGIT_ESR1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GSE10239_MEMORY_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, MIR6504_3P, MIR10399_5P, GSE10239_MEMORY_VS_DAY4.5_EFF_CD8_TCELL_UP, MIR6868_3P, MIR4700_5P, MIR7110_5P, MIR6887_3P, MIR4667_5P, MIR8089, MIR4468, DESCARTES_MAIN_FETAL_ANTIGEN_PRESENTING_CELLS, TRAVAGLINI_LUNG_CLUB_CELL

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

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A15	TMEM176A	Q96HP8	568
MS4A15	MS4A6E	Q96DS6	503
MS4A15	HIGD1B	Q9P298	502
MS4A15	MS4A5	Q9H3V2	474
MS4A15	PI15	O43692	428
MS4A15	S100A3	P33764	416
MS4A15	MS4A6A	Q9H2W1	408
MS4A15	SUSD4	Q5VX71	400
MS4A15	ZNF845	Q96IR2	397
MS4A15	PPP1R37	O75864	391
MS4A15	DYDC2	Q96IM9	377
MS4A15	ZNF721	Q8TF20	376
MS4A15	PPM1N	Q8N819	369
MS4A15	GPR146	Q96CH1	354
MS4A15	MANSC1	Q9H8J5	351

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MS4A15	ABCD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): SLC4A2 (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), LRRC8C (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), ABCD4 (Affinity Capture-MS), TMEM63B (Affinity Capture-MS), TMEM63A (Affinity Capture-MS), SLC12A9 (Affinity Capture-MS), RNFT1 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS)

ESM2 similar proteins: A6NGA9, A6NML5, A6QPF4, O95976, P0C6B7, P0C7T8, P0DP42, P11836, P13386, P19437, P20490, Q01362, Q2KJA5, Q32KQ5, Q3C2E2, Q3UNB8, Q3YBM2, Q4G068, Q5HZK2, Q5R8D6, Q5REZ0, Q5REZ6, Q60HE7, Q61168, Q7YQI4, Q80W35, Q8C3K5, Q8C6V3, Q8N5U1, Q920C4, Q925D4, Q96DS6, Q96HJ5, Q96HP8, Q96JQ5, Q96PG2, Q99N03, Q99N05, Q99N07, Q99N08

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, Q99N03, Q96PG1, Q96DS6, Q2YDM3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1529 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60773387:TGCA:T	acceptor_loss	1.0000
11:60773388:GCA:G	acceptor_loss	1.0000
11:60773390:A:G	acceptor_loss	1.0000
11:60773483:GG:G	donor_gain	1.0000
11:60773484:GG:G	donor_gain	1.0000
11:60773485:G:GG	donor_gain	1.0000
11:60773946:GTGCA:G	donor_gain	1.0000
11:60773948:GCA:G	donor_gain	1.0000
11:60773950:AG:A	donor_loss	1.0000
11:60773951:G:GG	donor_gain	1.0000
11:60773951:GT:G	donor_loss	1.0000
11:60775604:GCCT:G	acceptor_gain	1.0000
11:60767654:GC:G	donor_gain	0.9900
11:60767656:G:GG	donor_gain	0.9900
11:60771288:C:G	acceptor_gain	0.9900
11:60771289:A:AG	acceptor_gain	0.9900
11:60771290:G:GA	acceptor_gain	0.9900
11:60771290:GTTC:G	acceptor_gain	0.9900
11:60771346:TGGT:T	donor_loss	0.9900
11:60771347:GGT:G	donor_loss	0.9900
11:60771348:G:A	donor_loss	0.9900
11:60771349:T:A	donor_loss	0.9900
11:60771350:G:GG	donor_loss	0.9900
11:60773230:G:T	donor_gain	0.9900
11:60773380:T:A	acceptor_gain	0.9900
11:60773390:A:AG	acceptor_gain	0.9900
11:60773390:AG:A	acceptor_gain	0.9900
11:60773390:AGGT:A	acceptor_gain	0.9900
11:60773391:G:GC	acceptor_gain	0.9900
11:60773391:GG:G	acceptor_gain	0.9900

AlphaMissense

1568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60771291:T:C	F117L	0.963
11:60771293:C:A	F117L	0.963
11:60771293:C:G	F117L	0.963
11:60773422:A:C	S146R	0.934
11:60773424:C:A	S146R	0.934
11:60773424:C:G	S146R	0.934
11:60767575:A:C	S90R	0.917
11:60767577:C:A	S90R	0.917
11:60767577:C:G	S90R	0.917
11:60767552:G:A	G82D	0.902
11:60773887:G:C	E183D	0.897
11:60773887:G:T	E183D	0.897
11:60763929:T:C	F66L	0.892
11:60763931:C:A	F66L	0.892
11:60763931:C:G	F66L	0.892
11:60767543:T:C	I79T	0.889
11:60767641:T:A	W112R	0.888
11:60767641:T:C	W112R	0.888
11:60767653:T:C	C116R	0.884
11:60767638:T:C	F111L	0.860
11:60767640:C:A	F111L	0.860
11:60767640:C:G	F111L	0.860
11:60771304:G:A	G121E	0.850
11:60767566:G:C	G87R	0.843
11:60767551:G:C	G82R	0.842
11:60767573:G:A	G89D	0.840
11:60773915:T:C	F193L	0.833
11:60773917:C:A	F193L	0.833
11:60773917:C:G	F193L	0.833
11:60771292:T:C	F117S	0.829

dbSNP variants (sampled 300 via entrez): RS1000181424 (11:60756325 C>T), RS1000207249 (11:60761544 T>G), RS1000232750 (11:60756241 G>A), RS1000298965 (11:60773612 A>G,T), RS1000301091 (11:60760522 C>G,T), RS1000304778 (11:60772120 C>T), RS1000559094 (11:60761358 T>C), RS1000788099 (11:60755086 C>T), RS1000954591 (11:60763325 GA>G), RS1001281011 (11:60776410 C>T), RS1001321241 (11:60776911 A>G), RS1001509689 (11:60774921 G>GGACAAGCGGGGCTC), RS1001517625 (11:60771704 G>A,C), RS1001560664 (11:60767867 G>C), RS1001575340 (11:60765851 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010796_5337	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation	2
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
Aldehydes	increases expression	1
Endosulfan	decreases expression	1
Methapyrilene	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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