MS4A8

Summary

MS4A8 (membrane spanning 4-domains A8, HGNC:13380) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 8 (Q9BY19). 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 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 83661 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_031457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13380
Approved symbol	MS4A8
Name	membrane spanning 4-domains A8
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	MS4A4, CD20L5
Ensembl gene	ENSG00000166959
Ensembl biotype	protein_coding
OMIM	606549
Entrez	83661

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000300226, ENST00000450141, ENST00000525458, ENST00000529752, ENST00000532816, ENST00000532953, ENST00000533354, ENST00000533691, ENST00000534316, ENST00000855861, ENST00000855862

RefSeq mRNA: 1 — MANE Select: NM_031457 NM_031457

CCDS: CCDS7990

Canonical transcript exons

ENST00000300226 — 7 exons

Exon	Start	End
ENSE00001108190	60699612	60699775
ENSE00001108195	60708650	60708781
ENSE00001108198	60715310	60715807
ENSE00003484962	60703378	60703500
ENSE00003551899	60700860	60701079
ENSE00003611485	60706988	60707047
ENSE00003654964	60715021	60715134

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4483 / max 500.7696, expressed in 92 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114487	0.8254	54
114488	0.1850	29
114486	0.1576	38
114490	0.1336	22
114489	0.0806	18
114485	0.0661	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.55	gold quality
bronchial epithelial cell	CL:0002328	99.40	gold quality
ileal mucosa	UBERON:0000331	99.02	gold quality
bronchus	UBERON:0002185	98.80	gold quality
jejunal mucosa	UBERON:0000399	97.76	gold quality
duodenum	UBERON:0002114	94.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.69	gold quality
small intestine	UBERON:0002108	89.49	gold quality
epithelial cell of pancreas	CL:0000083	88.40	silver quality
fallopian tube	UBERON:0003889	87.78	gold quality
oviduct epithelium	UBERON:0004804	87.61	gold quality
pancreatic ductal cell	CL:0002079	87.55	silver quality
rectum	UBERON:0001052	86.98	gold quality
right lung	UBERON:0002167	86.15	gold quality
trachea	UBERON:0003126	85.95	gold quality
epithelium of nasopharynx	UBERON:0001951	83.52	gold quality
nasopharynx	UBERON:0001728	83.51	gold quality
gall bladder	UBERON:0002110	83.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.45	gold quality
mucosa of transverse colon	UBERON:0004991	78.69	gold quality
transverse colon	UBERON:0001157	77.55	gold quality
jejunum	UBERON:0002115	76.57	gold quality
pituitary gland	UBERON:0000007	76.51	gold quality
islet of Langerhans	UBERON:0000006	76.44	gold quality
colonic mucosa	UBERON:0000317	76.35	gold quality
mucosa of sigmoid colon	UBERON:0004993	76.19	gold quality
endometrium	UBERON:0001295	75.43	gold quality
left uterine tube	UBERON:0001303	75.17	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	68.79
E-CURD-114	yes	64.95
E-HCAD-1	yes	28.90
E-GEOD-130148	yes	14.84
E-MTAB-5061	yes	12.28
E-GEOD-81608	yes	9.94
E-ENAD-27	yes	4.78
E-GEOD-83139	no	3.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting MS4A8, 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-4778-3P	99.93	70.40	1818
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-5586-3P	95.51	67.00	805

Literature-anchored findings (GeneRIF, showing 1)

• MS4A8B is a novel differentiation marker of the intestinal epithelium that supports the maintenance of a physiological barrier function in the gut by modulating the transcriptome and by conferring an increased resistance to reactive oxygen species. (PMID:23348583)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ms4a8a	ENSMUSG00000024730
rattus_norvegicus	Ms4a8	ENSRNOG00000020939

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), MS4A7 (ENSG00000166927), MS4A14 (ENSG00000166928), MS4A5 (ENSG00000166930), MS4A15 (ENSG00000166961), MS4A10 (ENSG00000172689), TMEM212 (ENSG00000186329), MS4A13 (ENSG00000204979), MS4A18 (ENSG00000214782), MS4A4E (ENSG00000214787)

Protein

Protein identifiers

Membrane-spanning 4-domains subfamily A member 8 — Q9BY19 (reviewed: Q9BY19)

Alternative names: Four-span transmembrane protein 4, Membrane-spanning 4-domains subfamily A member 8B

All UniProt accessions (4): Q9BY19, E9PJN8, E9PQE1, H0YD94

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 hematopoietic tissues and cells lines.

Similarity. Belongs to the MS4A family.

RefSeq proteins (1): NP_113645* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030417	MS4A	Family

Pfam: PF04103

UniProt features (12 total): topological domain 5, transmembrane region 4, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY19-F1	71.55	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SABATES_COLORECTAL_ADENOMA_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN, FEVR_CTNNB1_TARGETS_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ZNF843_TARGET_GENES, GSE10094_LCMV_VS_LISTERIA_IND_EFF_CD4_TCELL_DN, MIR4778_3P, MIR4499, MIR384, GSE13306_RA_VS_UNTREATED_TCONV_DN, GSE13485_CTRL_VS_DAY3_YF17D_VACCINE_PBMC_UP, GSE17721_CTRL_VS_PAM3CSK4_24H_BMDC_UP

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

406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A8	MS4A6E	Q96DS6	921
MS4A8	MS4A4E	Q96PG1	713
MS4A8	CD2AP	Q9Y5K6	662
MS4A8	ABCA7	Q8IZY2	621
MS4A8	SORL1	Q92673	599
MS4A8	EPHA1	P21709	599
MS4A8	PICALM	Q13492	595
MS4A8	CLU	P10909	569
MS4A8	MS4A6A	Q9H2W1	544
MS4A8	CD33	P20138	521
MS4A8	ZCWPW1	Q9H0M4	513
MS4A8	BIN1	O00499	512
MS4A8	NME8	Q8N427	480
MS4A8	CASS4	Q9NQ75	480
MS4A8	SLC24A4	Q8NFF2	470

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0A7EPL0, A2RV66, A4QP16, A6QPF4, C4QM85, F4JYG0, O35892, P11836, P13386, P19437, P20490, P41739, P53762, P56645, P70326, P79778, Q01362, Q148B6, Q29131, Q3C1V0, Q3C2E2, Q3SA47, Q3UNB8, Q3V3Q4, Q3YBM2, Q5I2P1, Q5JT82, Q5R8D6, Q5R8E0, Q60HE7, Q68FU0, Q6A058, Q8BVM2, Q8N1N2, Q8NDZ0, Q8QGQ8, Q8WUU8, Q920C4, Q92540, Q96HJ5

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1605 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60708680:A:C	S145R	0.993
11:60708682:T:A	S145R	0.993
11:60708682:T:G	S145R	0.993
11:60706988:T:C	F115L	0.988
11:60706990:T:A	F115L	0.988
11:60706990:T:G	F115L	0.988
11:60703397:G:A	G80D	0.984
11:60703477:T:C	F107L	0.983
11:60703479:T:A	F107L	0.983
11:60703479:T:G	F107L	0.983
11:60703486:T:A	W110R	0.983
11:60703486:T:C	W110R	0.983
11:60703396:G:C	G80R	0.982
11:60707001:G:A	G119E	0.982
11:60708689:T:C	C148R	0.982
11:60703417:G:C	G87R	0.980
11:60708701:G:A	G152R	0.980
11:60708701:G:C	G152R	0.980
11:60701077:G:T	G73W	0.978
11:60708673:C:A	N142K	0.975
11:60708673:C:G	N142K	0.975
11:60703418:G:A	G87D	0.974
11:60715060:T:C	C192R	0.972
11:60708702:G:A	G152E	0.971
11:60703492:G:C	G112R	0.970
11:60707000:G:A	G119R	0.970
11:60707000:G:C	G119R	0.970
11:60703498:T:A	W114R	0.969
11:60703498:T:C	W114R	0.969
11:60701077:G:A	G73R	0.968

dbSNP variants (sampled 300 via entrez): RS1000290058 (11:60710170 C>G), RS1000405815 (11:60710437 G>A), RS1000418375 (11:60704799 A>C,T), RS1000509730 (11:60709495 C>T), RS1000606226 (11:60703282 T>C,G), RS1000661361 (11:60714792 G>A), RS1000775540 (11:60714990 C>A,T), RS1000911788 (11:60698384 T>C), RS1001184002 (11:60704317 C>T), RS1001303908 (11:60705563 G>A), RS1001729848 (11:60697939 A>T), RS1001746177 (11:60710559 G>C), RS1001793222 (11:60714452 A>G), RS1002100143 (11:60710939 C>T), RS1002283635 (11:60704726 C>G)

Disease associations

OMIM: gene MIM:606549 | 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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_VD91	300-19 GFP-MS4A8B	Cancer cell line
CVCL_VD96	BJAB GFP-MS4A8B	Cancer cell line	Female
CVCL_VE01	BJAB HA-MS4A8B	Cancer cell line	Female

Clinical trials (associated diseases)

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