MS4A5

Summary

MS4A5 (membrane spanning 4-domains A5, HGNC:13374) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 5 (Q9H3V2). 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. Though this member is not expressed in hematopoietic cells specifically, it may be involved in signal transduction like many of its related family members. The gene encoding this protein is localized to 11q12, among a cluster of family members.

Source: NCBI Gene 64232 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_023945

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13374
Approved symbol	MS4A5
Name	membrane spanning 4-domains A5
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	CD20L2
Ensembl gene	ENSG00000166930
Ensembl biotype	protein_coding
OMIM	606499
Entrez	64232

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000300190, ENST00000528093, ENST00000528905, ENST00000531403, ENST00000533885, ENST00000534071

RefSeq mRNA: 1 — MANE Select: NM_023945 NM_023945

CCDS: CCDS7987

Canonical transcript exons

ENST00000300190 — 5 exons

Exon	Start	End
ENSE00001107902	60429572	60429827
ENSE00001107903	60433765	60433917
ENSE00001107907	60430796	60430924
ENSE00003591100	60447649	60447792
ENSE00003687229	60432411	60432467

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 97.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0751 / max 90.2170, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114470	0.0421	4
114471	0.0330	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.65	gold quality
male germ cell	CL:0000015	95.52	gold quality
left testis	UBERON:0004533	91.81	gold quality
right testis	UBERON:0004534	90.97	gold quality
testis	UBERON:0000473	88.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.20	gold quality
buccal mucosa cell	CL:0002336	84.79	gold quality
adult organism	UBERON:0007023	78.46	gold quality
tongue squamous epithelium	UBERON:0006919	63.11	gold quality
olfactory bulb	UBERON:0002264	60.47	gold quality
type B pancreatic cell	CL:0000169	60.26	gold quality
diaphragm	UBERON:0001103	56.18	gold quality
kidney epithelium	UBERON:0004819	53.01	gold quality
thymus	UBERON:0002370	50.86	gold quality
epithelial cell of pancreas	CL:0000083	50.31	gold quality
quadriceps femoris	UBERON:0001377	49.98	gold quality
hair follicle	UBERON:0002073	49.98	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.78	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
vastus lateralis	UBERON:0001379	48.93	gold quality
oviduct epithelium	UBERON:0004804	48.88	gold quality
myocardium	UBERON:0002349	48.87	gold quality
cerebellar vermis	UBERON:0004720	48.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oocyte	CL:0000023	48.39	gold quality
cervix epithelium	UBERON:0004801	48.39	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.93

Regulation

Is transcription factor: no

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	Ms4a5	ENSMUSG00000054523
rattus_norvegicus	Ms4a5	ENSRNOG00000025857

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), MS4A7 (ENSG00000166927), MS4A14 (ENSG00000166928), MS4A8 (ENSG00000166959), MS4A15 (ENSG00000166961), MS4A10 (ENSG00000172689), TMEM212 (ENSG00000186329), MS4A13 (ENSG00000204979), MS4A18 (ENSG00000214782), MS4A4E (ENSG00000214787)

Protein

Protein identifiers

Membrane-spanning 4-domains subfamily A member 5 — Q9H3V2 (reviewed: Q9H3V2)

Alternative names: CD20 antigen-like 2, Testis-expressed transmembrane protein 4

All UniProt accessions (5): Q9H3V2, A0A0B4J228, E9PKT5, H0YD29, H0YDK1

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 at high level in the testis. Detected also in the pancreas, heart and in the brain.

Similarity. Belongs to the MS4A family.

RefSeq proteins (1): NP_076434* (*=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-Q9H3V2-F1	75.96	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GNF2_CCNA1, WEBER_METHYLATED_LCP_IN_SPERM_UP, MODULE_48, MODULE_95, TEF_Q6, MODULE_163, BRCA1_DN.V1_DN, GSE1460_INTRATHYMIC_T_PROGENITOR_VS_DP_THYMOCYTE_UP, WEBER_METHYLATED_LCP_IN_FIBROBLAST_UP, GSE37416_CTRL_VS_0H_F_TULARENSIS_LVS_NEUTROPHIL_UP, GSE3982_EOSINOPHIL_VS_MAST_CELL_UP, GSE3982_MAST_CELL_VS_BASOPHIL_DN, GSE3982_BCELL_VS_BASOPHIL_DN, GSE6269_E_COLI_VS_STREP_PNEUMO_INF_PBMC_UP, chr11q12

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

192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A5	MS4A2	Q01362	858
MS4A5	OOSP4B	A0A2R8Y4Y8	695
MS4A5	TMEM176A	Q96HP8	597
MS4A5	MS4A6E	Q96DS6	584
MS4A5	OOSP2	Q86WS3	550
MS4A5	GARIN2	Q8N9W8	549
MS4A5	MS4A18	Q3C1V0	532
MS4A5	MS4A12	Q9NXJ0	478
MS4A5	MS4A15	Q8N5U1	474
MS4A5	MS4A4E	Q96PG1	473
MS4A5	SVBP	Q8N300	460
MS4A5	MS4A1	P08984	459
MS4A5	TMEM86B	Q8N661	452
MS4A5	LRRC36	Q1X8D7	435
MS4A5	ATP10D	Q9P241	428

IntAct

2 interactions, top by confidence:

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

BioGRID (1): MS4A5 (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, P11836, P13386, P19437, P20490, Q01362, Q3C1V0, Q3C2E2, Q3UPL6, Q8N5U1, Q920C4, Q96JA4, Q96JQ5, Q99N05, Q99N07, Q99N09, Q99N10, Q9BY19, Q9H2W1, Q9H3V2, Q9NXJ0, Q5REZ6, Q96HJ5, Q96PG2, Q99N08, Q9GZW8, Q96PG1, Q96DS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

567 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60429825:GGG:G	donor_gain	0.9900
11:60429826:GGG:G	donor_gain	0.9900
11:60432409:A:AG	acceptor_gain	0.9900
11:60432410:G:GG	acceptor_gain	0.9900
11:60429826:GG:G	donor_gain	0.9800
11:60429826:GGGTA:G	donor_loss	0.9800
11:60429827:GG:G	donor_gain	0.9800
11:60429827:GGTA:G	donor_loss	0.9800
11:60429828:G:GG	donor_gain	0.9800
11:60429828:GTAA:G	donor_loss	0.9800
11:60432410:GTTC:G	acceptor_gain	0.9800
11:60429830:A:AG	donor_loss	0.9600
11:60432410:GTTCA:G	acceptor_gain	0.9500
11:60429832:G:GG	donor_gain	0.9300
11:60432410:GTT:G	acceptor_gain	0.9300
11:60432464:TCTGG:T	donor_loss	0.9300
11:60432466:TGGTG:T	donor_loss	0.9300
11:60432467:GGTGA:G	donor_loss	0.9300
11:60432468:G:GG	donor_gain	0.9300
11:60432469:TGA:T	donor_loss	0.9300
11:60432470:GAGT:G	donor_loss	0.9300
11:60432471:A:AT	donor_loss	0.9300
11:60432472:G:A	donor_loss	0.9300
11:60433672:C:G	donor_gain	0.9300
11:60433890:GT:G	donor_gain	0.9300
11:60429823:TAGGG:T	donor_gain	0.9200
11:60429824:AGGG:A	donor_gain	0.9200
11:60429825:GGGG:G	donor_gain	0.9200
11:60429831:A:AG	donor_gain	0.9100
11:60433655:GCAT:G	donor_gain	0.9000

AlphaMissense

1305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60433795:A:C	S124R	0.991
11:60433797:T:A	S124R	0.991
11:60433797:T:G	S124R	0.991
11:60430910:T:A	W90R	0.987
11:60430910:T:C	W90R	0.987
11:60430815:G:A	G58E	0.985
11:60432411:T:C	F95L	0.982
11:60432413:C:A	F95L	0.982
11:60432413:C:G	F95L	0.982
11:60430887:T:A	I82K	0.978
11:60430901:T:G	Y87D	0.978
11:60433816:G:A	G131R	0.977
11:60433816:G:C	G131R	0.977
11:60430814:G:A	G58R	0.976
11:60430814:G:C	G58R	0.976
11:60447676:A:C	S174R	0.976
11:60447678:C:A	S174R	0.976
11:60447678:C:G	S174R	0.976
11:60430835:G:A	G65R	0.975
11:60430835:G:C	G65R	0.975
11:60430836:G:A	G65E	0.975
11:60433864:T:A	C147S	0.973
11:60433865:G:C	C147S	0.973
11:60433788:T:A	N121K	0.972
11:60433788:T:G	N121K	0.972
11:60432424:G:A	G99E	0.971
11:60430913:G:C	G91R	0.969
11:60430899:G:A	G86E	0.967
11:60433804:G:A	G127R	0.966
11:60433804:G:C	G127R	0.966

dbSNP variants (sampled 300 via entrez): RS1000044168 (11:60428472 T>C), RS1000136976 (11:60444395 C>T), RS1000352963 (11:60428737 G>C), RS1000742442 (11:60443191 G>A,T), RS1000864143 (11:60448036 GT>G), RS1000884882 (11:60436705 GA>G), RS1001026844 (11:60443441 T>C), RS1001153928 (11:60430828 T>C,G), RS1001177489 (11:60427652 A>G), RS1001208550 (11:60428085 A>G), RS1001411916 (11:60444288 C>A,T), RS1001412934 (11:60433640 C>G), RS1001546583 (11:60437202 C>G,T), RS1001894472 (11:60441438 G>A), RS1001928555 (11:60447989 A>G)

Disease associations

OMIM: gene MIM:606499 | 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
GCST007471_3	Short-term memory (digit-span task)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004335	short-term memory

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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