MS4A14

Summary

MS4A14 (membrane spanning 4-domains A14, HGNC:30706) is a protein-coding gene on chromosome 11q12.2, encoding Membrane-spanning 4-domains subfamily A member 14 (Q96JA4). 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 84689 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_032597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30706
Approved symbol	MS4A14
Name	membrane spanning 4-domains A14
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	NYD-SP21, FLJ32856, DKFZp434H092
Ensembl gene	ENSG00000166928
Ensembl biotype	protein_coding
Entrez	84689

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 nonsense_mediated_decay

ENST00000300187, ENST00000395001, ENST00000395005, ENST00000525397, ENST00000526375, ENST00000527841, ENST00000530662, ENST00000531783, ENST00000531787, ENST00000531949, ENST00000534688

RefSeq mRNA: 4 — MANE Select: NM_032597 NM_001079692, NM_001261827, NM_001261828, NM_032597

CCDS: CCDS31569, CCDS41652, CCDS58136, CCDS73295

Canonical transcript exons

ENST00000300187 — 5 exons

Exon	Start	End
ENSE00001520267	60415437	60417756
ENSE00001520288	60396459	60396716
ENSE00003564164	60400404	60400454
ENSE00003579565	60402912	60403061
ENSE00003721553	60397852	60397980

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1992 / max 151.6101, expressed in 8 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114459	25.6287	466
114468	0.1786	4
114469	0.0135	5
114467	0.0072	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.65	gold quality
left testis	UBERON:0004533	95.83	gold quality
right testis	UBERON:0004534	95.64	gold quality
testis	UBERON:0000473	93.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.69	gold quality
monocyte	CL:0000576	88.43	gold quality
granulocyte	CL:0000094	88.19	gold quality
leukocyte	CL:0000738	87.88	gold quality
epithelial cell of pancreas	CL:0000083	84.25	silver quality
adult organism	UBERON:0007023	82.65	gold quality
spleen	UBERON:0002106	79.55	gold quality
blood	UBERON:0000178	79.01	gold quality
right coronary artery	UBERON:0001625	77.75	gold quality
upper lobe of left lung	UBERON:0008952	76.88	gold quality
upper lobe of lung	UBERON:0008948	76.02	gold quality
right adrenal gland cortex	UBERON:0035827	74.86	gold quality
ileal mucosa	UBERON:0000331	73.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.29	gold quality
omental fat pad	UBERON:0010414	73.27	gold quality
peritoneum	UBERON:0002358	73.18	gold quality
left adrenal gland cortex	UBERON:0035825	72.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.94	gold quality
right adrenal gland	UBERON:0001233	72.40	gold quality
left coronary artery	UBERON:0001626	72.16	gold quality
left adrenal gland	UBERON:0001234	71.93	gold quality
adrenal cortex	UBERON:0001235	71.31	gold quality
descending thoracic aorta	UBERON:0002345	71.08	gold quality
adipose tissue	UBERON:0001013	70.91	gold quality
coronary artery	UBERON:0001621	70.88	gold quality
vermiform appendix	UBERON:0001154	70.86	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	393.76
E-HCAD-35	yes	11.30
E-ANND-3	yes	11.00
E-CURD-119	yes	5.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting MS4A14, 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-3185	99.99	68.12	1959
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6755-3P	98.61	66.90	834
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-493-3P	97.50	66.44	731

Literature-anchored findings (GeneRIF, showing 1)

• Interaction analysis demonstrated that the following genotypes: MS4A14 DI+II, SLC2A DI+II and ABCB 5 CG+GG, were associated with a prothrombin time >/=12 sec and with Recurrent pregnancy loss (RPL) risk (PMID:29956771)

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	Ms4a14	ENSMUSG00000099398
rattus_norvegicus	Ms4a14	ENSRNOG00000025805

Paralogs (16): MS4A12 (ENSG00000071203), MS4A6A (ENSG00000110077), MS4A4A (ENSG00000110079), MS4A3 (ENSG00000149516), MS4A2 (ENSG00000149534), MS4A1 (ENSG00000156738), MS4A6E (ENSG00000166926), MS4A7 (ENSG00000166927), 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 14 — Q96JA4 (reviewed: Q96JA4)

Alternative names: Testis development protein NYD-SP21

All UniProt accessions (8): Q96JA4, A0A0A0MS57, E9PIL9, E9PPA2, E9PRA6, E9PRG6, F6X344, H0YD53

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 (4)

UniProt ID	Names	Canonical?
Q96JA4-1	1	yes
Q96JA4-2	2
Q96JA4-4	3
Q96JA4-5	4

RefSeq proteins (4): NP_001073160, NP_001248756, NP_001248757, NP_115986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030417	MS4A	Family

Pfam: PF04103

UniProt features (23 total): compositionally biased region 7, splice variant 5, transmembrane region 4, region of interest 4, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JA4-F1	48.59	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): MODULE_207, MIR153_5P, MIR548AH_5P, MIR4778_3P, GSE11864_CSF1_IFNG_VS_CSF1_IFNG_PAM3CYS_IN_MAC_DN, MIR4435, MIR6755_3P, MIR6886_3P, MIR331_3P, MANNE_COVID19_COMBINED_COHORT_VS_HEALTHY_DONOR_PLATELETS_DN, DESCARTES_FETAL_ADRENAL_MYELOID_CELLS, DESCARTES_FETAL_CEREBELLUM_MICROGLIA, DESCARTES_FETAL_CEREBRUM_MICROGLIA, DESCARTES_FETAL_HEART_MYELOID_CELLS, DESCARTES_FETAL_INTESTINE_MYELOID_CELLS

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

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MS4A14	MS4A18	Q3C1V0	690
MS4A14	OOSP4B	A0A2R8Y4Y8	620
MS4A14	MS4A6E	Q96DS6	447
MS4A14	OR51Q1	Q8NH59	444
MS4A14	ATP8B3	O60423	426
MS4A14	SPACDR	Q8IZ16	400
MS4A14	OOSP2	Q86WS3	377
MS4A14	OR2L8	Q8NGY9	377
MS4A14	TVP23C	Q96ET8	375
MS4A14	RGPD1	P0C839	375
MS4A14	ANKDD1B	A6NHY2	374
MS4A14	MAGEB16	A2A368	370
MS4A14	A0A0A6YYB9	A0A0A6YYB9	370
MS4A14	LACRT	Q9GZZ8	366
MS4A14	MOB3C	Q70IA8	348

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CLDN19	MS4A14	psi-mi:“MI:0915”(physical association)	0.560
CDIPT	MS4A14	psi-mi:“MI:0915”(physical association)	0.560
TMEM54	MS4A14	psi-mi:“MI:0915”(physical association)	0.560
SEC22A	MS4A14	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	MS4A14	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	MS4A14	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	MS4A14	psi-mi:“MI:0915”(physical association)	0.000
CLDN19	MS4A14	psi-mi:“MI:0915”(physical association)	0.000
CDIPT	MS4A14	psi-mi:“MI:0915”(physical association)	0.000
TMEM54	MS4A14	psi-mi:“MI:0915”(physical association)	0.000
SEC22A	MS4A14	psi-mi:“MI:0915”(physical association)	0.000
TMEM86B	MS4A14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): MS4A14 (Two-hybrid), MS4A14 (Two-hybrid), MS4A14 (Two-hybrid), MS4A14 (Two-hybrid), TMEM86B (Two-hybrid), GIMAP5 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1613 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60400403:GTTT:G	acceptor_gain	1.0000
11:60403032:A:AG	donor_gain	1.0000
11:60403059:ATT:A	donor_gain	1.0000
11:60403060:TT:T	donor_gain	1.0000
11:60403062:G:GG	donor_gain	1.0000
11:60393786:GA:G	acceptor_gain	0.9900
11:60397981:G:GG	donor_gain	0.9900
11:60400402:A:AG	acceptor_gain	0.9900
11:60400403:G:GA	acceptor_gain	0.9900
11:60400403:GT:G	acceptor_gain	0.9900
11:60400403:GTT:G	acceptor_gain	0.9900
11:60400403:GTTTA:G	acceptor_gain	0.9900
11:60402907:TTCA:T	acceptor_loss	0.9900
11:60402908:TCAG:T	acceptor_loss	0.9900
11:60402910:A:AG	acceptor_gain	0.9900
11:60402910:AG:A	acceptor_gain	0.9900
11:60402911:G:A	acceptor_loss	0.9900
11:60402911:G:GG	acceptor_gain	0.9900
11:60402911:GG:G	acceptor_gain	0.9900
11:60403029:GAAA:G	donor_gain	0.9900
11:60403032:A:G	donor_gain	0.9900
11:60403044:A:AG	donor_gain	0.9900
11:60403045:G:GG	donor_gain	0.9900
11:60403058:CATT:C	donor_gain	0.9900
11:60403061:TGTAA:T	donor_loss	0.9900
11:60403062:G:GC	donor_loss	0.9900
11:60403063:T:TG	donor_loss	0.9900
11:60403064:A:AT	donor_loss	0.9900
11:60405809:GT:G	donor_gain	0.9900
11:60415432:TATA:T	acceptor_loss	0.9900

AlphaMissense

4467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60402942:A:C	S117R	0.979
11:60402944:C:A	S117R	0.979
11:60402944:C:G	S117R	0.979
11:60397966:T:A	W85R	0.977
11:60397966:T:C	W85R	0.977
11:60397969:G:A	G86R	0.954
11:60397969:G:C	G86R	0.954
11:60400404:T:C	F90L	0.948
11:60400406:T:A	F90L	0.948
11:60400406:T:G	F90L	0.948
11:60416381:G:C	W471C	0.948
11:60416381:G:T	W471C	0.948
11:60415587:T:C	F207L	0.945
11:60415589:C:A	F207L	0.945
11:60415589:C:G	F207L	0.945
11:60397885:G:C	G58R	0.943
11:60402984:A:C	S131R	0.943
11:60402986:C:A	S131R	0.943
11:60402986:C:G	S131R	0.943
11:60397957:T:G	Y82D	0.940
11:60402963:G:A	G124R	0.938
11:60402963:G:C	G124R	0.938
11:60402955:C:A	A121E	0.933
11:60415597:T:C	L210S	0.931
11:60415590:T:C	F208L	0.927
11:60415592:C:A	F208L	0.927
11:60415592:C:G	F208L	0.927
11:60402952:T:A	V120D	0.923
11:60402958:T:A	I122K	0.923
11:60397891:G:A	G60R	0.921

dbSNP variants (sampled 300 via entrez): RS1000147224 (11:60411093 G>A), RS1000160125 (11:60405873 T>C), RS1000202486 (11:60408746 A>G), RS1000242507 (11:60410911 T>C), RS1000478275 (11:60405920 T>C), RS1000636935 (11:60398796 G>C), RS1000663002 (11:60407497 A>T), RS1000701782 (11:60405230 C>A), RS1000729781 (11:60398536 G>A), RS1000827299 (11:60395049 A>G), RS1000952005 (11:60401066 G>T), RS1000972733 (11:60414224 A>G), RS1001111197 (11:60395267 G>A), RS1001383077 (11:60401380 T>C), RS1002059059 (11:60404334 G>A,C,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:190300

GenCC curated gene-disease

Mondo (1): essential tremor (MONDO:0003233)

Orphanet (1): NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003262_564	Post bronchodilator FEV1	5.000000e-06
GCST009391_967	Metabolite levels	3.000000e-06
GCST90002393_230	Monocyte count	8.000000e-24

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0005091	monocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Phthalic Acids	increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
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