MS4A12

Summary

MS4A12 (membrane spanning 4-domains A12, HGNC:13370) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 12 (Q9NXJ0). May be involved in signal transduction as a component of a multimeric receptor complex.

The protein encoded by this gene is a cell surface protein found primarily in the apical membrane of colonocytes. Silencing of this gene in colon cancer cells inhibits the proliferation, cell motility, and chemotactic invasion of cells. This gene is part of a cluster of similar genes found on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54860 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_017716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13370
Approved symbol	MS4A12
Name	membrane spanning 4-domains A12
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	Ms4a10, FLJ20217
Ensembl gene	ENSG00000071203
Ensembl biotype	protein_coding
OMIM	606550
Entrez	54860

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000016913, ENST00000525951, ENST00000526784, ENST00000530007, ENST00000537076, ENST00000880034, ENST00000880035, ENST00000971815, ENST00000971816, ENST00000971817

RefSeq mRNA: 2 — MANE Select: NM_017716 NM_001164470, NM_017716

CCDS: CCDS53638, CCDS7988

Canonical transcript exons

ENST00000016913 — 7 exons

Exon	Start	End
ENSE00000720002	60501045	60501182
ENSE00000720006	60501983	60502039
ENSE00000720012	60503701	60503817
ENSE00000720020	60506728	60506838
ENSE00001107922	60507020	60507430
ENSE00001107923	60497313	60497594
ENSE00001107924	60492778	60492828

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 99.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0588 / max 40.4611, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114478	0.0588	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.18	gold quality
rectum	UBERON:0001052	99.14	gold quality
colonic mucosa	UBERON:0000317	98.86	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.53	gold quality
transverse colon	UBERON:0001157	89.30	gold quality
ileal mucosa	UBERON:0000331	86.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.03	gold quality
vermiform appendix	UBERON:0001154	77.86	gold quality
large intestine	UBERON:0000059	76.43	gold quality
colon	UBERON:0001155	75.54	gold quality
caecum	UBERON:0001153	72.14	gold quality
colonic epithelium	UBERON:0000397	71.49	gold quality
intestine	UBERON:0000160	66.34	gold quality
diaphragm	UBERON:0001103	63.06	gold quality
tibialis anterior	UBERON:0001385	58.31	silver quality
smooth muscle tissue	UBERON:0001135	58.22	gold quality
quadriceps femoris	UBERON:0001377	55.99	gold quality
vastus lateralis	UBERON:0001379	55.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	55.74	gold quality
nasal cavity epithelium	UBERON:0005384	52.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	52.02	gold quality
left ventricle myocardium	UBERON:0006566	51.22	gold quality
deltoid	UBERON:0001476	51.04	gold quality
right coronary artery	UBERON:0001625	50.59	gold quality
thymus	UBERON:0002370	49.70	gold quality
myocardium	UBERON:0002349	49.68	gold quality
pancreatic ductal cell	CL:0002079	49.55	silver quality
epithelial cell of pancreas	CL:0000083	49.39	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	1264.28
E-ANND-3	yes	14.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2

miRNA regulators (miRDB)

25 targeting MS4A12, 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-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-151A-3P	95.52	65.29	516
HSA-MIR-4670-5P	77.22	63.41	20

Literature-anchored findings (GeneRIF, showing 4)

• MS4A12 is a colon-selective store-operated calcium channel promoting malignant cell processes. (PMID:18451174)
• RNA interference of CDX1 and CDX2 and chromatin immunoprecipitation in colon cancer cells revealed that MS4A12 transcript and protein expression is essentially dependent on the presence of endogenous CDX2. (PMID:19781065)
• In early stage colon cancer, the patients with low MS4A12 expression had a poor survival, while in advanced stage colon cancer MS412 had little prognostic value. (PMID:27881006)
• CLCA4 and MS4A12 as the significant gene biomarkers of primary colorectal cancer. (PMID:32797167)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ms4a12	ENSMUSG00000101031
rattus_norvegicus	Ms4a12	ENSRNOG00000026387

Paralogs (16): MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), 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 12 — Q9NXJ0 (reviewed: Q9NXJ0)

All UniProt accessions (3): Q9NXJ0, E9PIX5, E9PNI3

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 (2)

UniProt ID	Names	Canonical?
Q9NXJ0-1	1	yes
Q9NXJ0-2	2

RefSeq proteins (2): NP_001157942, NP_060186* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030417	MS4A	Family

Pfam: PF04103

UniProt features (16 total): topological domain 5, transmembrane region 4, sequence conflict 3, chain 1, region of interest 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXJ0-F1	71.30	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): SABATES_COLORECTAL_ADENOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, BRUINS_UVC_RESPONSE_LATE, FEVR_CTNNB1_TARGETS_UP, PRC2_EZH2_UP.V1_DN, MIR616_5P, MIR371B_5P, MIR373_5P, MIR651_3P, MIR450B_5P, MIR4477A, MIR4516, MIR4477B, MIR6780A_5P, MIR4517

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

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

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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A12	MS4A6E	Q96DS6	927
MS4A12	MS4A4E	Q96PG1	915
MS4A12	ZG16	O60844	744
MS4A12	GUCA2A	Q02747	652
MS4A12	CLCA4	Q14CN2	624
MS4A12	GUCA2B	Q16661	621
MS4A12	TMIGD1	Q6UXZ0	601
MS4A12	KRT20	P35900	563
MS4A12	AQP8	O94778	544
MS4A12	OOSP4B	A0A2R8Y4Y8	507
MS4A12	REG4	Q9BYZ8	498
MS4A12	SLC26A3	P40879	488
MS4A12	TMEM176A	Q96HP8	487
MS4A12	MS4A5	Q9H3V2	478
MS4A12	TFF3	Q07654	460

IntAct

17 interactions, top by confidence:

A	B	Type	Score
MS4A12	MALL	psi-mi:“MI:0915”(physical association)	0.720
PLLP	MS4A12	psi-mi:“MI:0915”(physical association)	0.720
MS4A12	PLLP	psi-mi:“MI:0915”(physical association)	0.720
MALL	MS4A12	psi-mi:“MI:0915”(physical association)	0.720
MS4A12	FAM3A	psi-mi:“MI:0915”(physical association)	0.560
FAM3A	MS4A12	psi-mi:“MI:0915”(physical association)	0.560
MS4A12	STOM	psi-mi:“MI:0914”(association)	0.350
MALL	MS4A12	psi-mi:“MI:0915”(physical association)	0.000
PLLP	MS4A12	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): MS4A12 (Two-hybrid), MS4A12 (Two-hybrid), FAM3A (Two-hybrid), PLLP (Two-hybrid), MALL (Two-hybrid), MYADM (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), STOM (Affinity Capture-MS), TMEM63B (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

823 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60503697:T:G	acceptor_gain	1.0000
11:60503697:TTAG:T	acceptor_loss	1.0000
11:60503700:G:GT	acceptor_loss	1.0000
11:60503813:CCGTG:C	donor_gain	1.0000
11:60503815:GTG:G	donor_gain	1.0000
11:60503816:TG:T	donor_gain	1.0000
11:60503817:GG:G	donor_gain	1.0000
11:60503818:G:GG	donor_gain	1.0000
11:60503819:TAA:T	donor_loss	1.0000
11:60506719:T:TA	acceptor_gain	1.0000
11:60506726:A:AG	acceptor_gain	1.0000
11:60506727:G:GG	acceptor_gain	1.0000
11:60492829:G:GG	donor_gain	0.9900
11:60501085:G:GT	donor_gain	0.9900
11:60501120:G:GT	donor_gain	0.9900
11:60503686:T:A	acceptor_gain	0.9900
11:60503690:A:AG	acceptor_gain	0.9900
11:60503691:T:G	acceptor_gain	0.9900
11:60503696:A:AG	acceptor_gain	0.9900
11:60503699:A:AG	acceptor_gain	0.9900
11:60503700:G:GG	acceptor_gain	0.9900
11:60503700:GGT:G	acceptor_gain	0.9900
11:60503814:CGTG:C	donor_gain	0.9900
11:60503815:GTGG:G	donor_gain	0.9900
11:60503816:TGGT:T	donor_gain	0.9900
11:60503817:GGTA:G	donor_gain	0.9900
11:60506718:AT:A	acceptor_gain	0.9900
11:60506719:T:G	acceptor_gain	0.9900
11:60506724:TCA:T	acceptor_loss	0.9900
11:60506725:CA:C	acceptor_loss	0.9900

AlphaMissense

1744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60503731:A:C	S168R	0.987
11:60503733:T:A	S168R	0.987
11:60503733:T:G	S168R	0.987
11:60501983:T:C	F139L	0.986
11:60501985:T:A	F139L	0.986
11:60501985:T:G	F139L	0.986
11:60501132:T:C	F122L	0.985
11:60501134:T:A	F122L	0.985
11:60501134:T:G	F122L	0.985
11:60501168:T:A	W134R	0.972
11:60501168:T:C	W134R	0.972
11:60501064:G:A	G99E	0.969
11:60501996:G:A	G143D	0.968
11:60503773:G:C	D182H	0.966
11:60503710:A:C	S161R	0.964
11:60503712:C:A	S161R	0.964
11:60503712:C:G	S161R	0.964
11:60503752:G:A	G175R	0.964
11:60503752:G:C	G175R	0.964
11:60501085:G:A	G106E	0.963
11:60501084:G:A	G106R	0.961
11:60501084:G:C	G106R	0.961
11:60501063:G:A	G99R	0.959
11:60501063:G:C	G99R	0.959
11:60501159:T:G	Y131D	0.959
11:60503724:C:A	N165K	0.958
11:60503724:C:G	N165K	0.958
11:60503753:G:A	G175E	0.954
11:60503774:A:C	D182A	0.953
11:60501172:G:A	G135D	0.947

dbSNP variants (sampled 300 via entrez): RS1000079688 (11:60492036 G>A,T), RS1000278311 (11:60500402 A>G), RS1000505605 (11:60506498 T>C), RS1000600994 (11:60501683 TA>T,TAA), RS1000811143 (11:60491128 C>T), RS1000885946 (11:60507025 C>G), RS1000913051 (11:60495423 C>T), RS1001097774 (11:60491238 C>A,G,T), RS1001499399 (11:60501607 G>A), RS1001500376 (11:60499911 T>G), RS1001614037 (11:60501813 A>G), RS1001802983 (11:60500755 T>C), RS1001812810 (11:60491064 C>A,T), RS1002015341 (11:60496156 A>G), RS1002057714 (11:60495300 C>T)

Disease associations

OMIM: gene MIM:606550 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004721_17	Congenital heart disease (maternal effect)	4.000000e-07
GCST009205_11	Supramarginal gyrus volume	9.000000e-06
GCST90002388_537	Lymphocyte count	2.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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