ERVMER34-1

Summary

ERVMER34-1 (endogenous retrovirus group MER34 member 1, envelope, HGNC:42970) is a protein-coding gene on chromosome 4q12, encoding Endogenous retroviral envelope protein HEMO (Q9H9K5). Endogenous envelope proteins originate from retroviral envelope proteins, which mediate receptor recognition and membrane fusion during early infection.

Predicted to be located in extracellular region and plasma membrane.

Source: NCBI Gene 100288413 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_001242690

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:42970
Approved symbol	ERVMER34-1
Name	endogenous retrovirus group MER34 member 1, envelope
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	envMER34, HEMO
Ensembl gene	ENSG00000226887
Ensembl biotype	protein_coding
Entrez	100288413

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000440542, ENST00000443173, ENST00000454756, ENST00000898593, ENST00000898594, ENST00000898595, ENST00000915231, ENST00000915232, ENST00000915233, ENST00000915234, ENST00000915235, ENST00000915236, ENST00000915237, ENST00000915238, ENST00000944608, ENST00000944609

RefSeq mRNA: 2 — MANE Select: NM_001242690 NM_001242690, NM_024534

Canonical transcript exons

ENST00000443173 — 3 exons

Exon	Start	End
ENSE00001611982	52750930	52751069
ENSE00001639233	52751343	52751425
ENSE00001782809	52742553	52745943

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 84.70.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8394 / max 99.6788, expressed in 597 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52112	1.0356	405
52117	0.3852	215
52113	0.2465	118
52115	0.1556	63
52114	0.0165	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	84.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.90	gold quality
metanephros cortex	UBERON:0010533	69.00	gold quality
renal glomerulus	UBERON:0000074	64.73	gold quality
metanephric glomerulus	UBERON:0004736	64.72	silver quality
apex of heart	UBERON:0002098	64.12	gold quality
heart left ventricle	UBERON:0002084	64.07	gold quality
metanephros	UBERON:0000081	63.69	gold quality
cardiac ventricle	UBERON:0002082	63.33	gold quality
decidua	UBERON:0002450	63.16	silver quality
nephron tubule	UBERON:0001231	63.14	silver quality
lower esophagus mucosa	UBERON:0035834	62.98	gold quality
adult mammalian kidney	UBERON:0000082	62.75	gold quality
right ovary	UBERON:0002118	61.86	gold quality
cortex of kidney	UBERON:0001225	61.77	gold quality
left ovary	UBERON:0002119	61.60	gold quality
kidney epithelium	UBERON:0004819	61.39	silver quality
esophagus mucosa	UBERON:0002469	61.36	gold quality
pigmented layer of retina	UBERON:0001782	60.58	gold quality
ovary	UBERON:0000992	60.17	gold quality
kidney	UBERON:0002113	60.03	gold quality
stromal cell of endometrium	CL:0002255	59.94	gold quality
endometrium	UBERON:0001295	58.86	gold quality
islet of Langerhans	UBERON:0000006	58.85	gold quality
heart	UBERON:0000948	58.63	gold quality
right lung	UBERON:0002167	57.45	gold quality
seminal vesicle	UBERON:0000998	57.23	silver quality
superficial temporal artery	UBERON:0001614	56.46	gold quality
pancreas	UBERON:0001264	55.86	gold quality
female reproductive system	UBERON:0000474	55.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting ERVMER34-1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-938	97.41	68.28	656
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-6813-3P	95.78	63.78	540
HSA-MIR-371B-3P	94.48	66.59	345
HSA-MIR-8088	89.27	73.01	56

Cross-species orthologs

0 orthologs

Paralogs (7): ERV3-1 (ENSG00000213462), ERVW-1 (ENSG00000242950), ERVFRD-1 (ENSG00000244476), ERVV-2 (ENSG00000268964), ERVV-1 (ENSG00000269526), (ENSG00000293569), (ENSG00000293570)

Protein

Protein identifiers

Endogenous retroviral envelope protein HEMO — Q9H9K5 (reviewed: Q9H9K5)

Alternative names: Endogenous retrovirus group MER34 member 1 Env polyprotein, HERV-MER_4q12 provirus ancestral Env polyprotein, Human endogenous MER34 (medium-reiteration-frequency-family-34) open reading frame, Human endogenous MER34 ORF

All UniProt accessions (1): Q9H9K5

UniProt curated annotations — full annotation on UniProt →

Function. Endogenous envelope proteins originate from retroviral envelope proteins, which mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed at high level in the placenta and stem cells (at protein level). Also expressed in the kidney but at a lower level. Endogenous retroviral envelope protein HEMO, secreted form: Present in the blood of pregnant women (at protein level).

Post-translational modifications. N-glycosylated. Cleaved by some metalloproteinase at 432-Gln-Arg-433 (mainly) or 433-Arg-Gln-434, leading to release the secreted form (Endogenous retroviral envelope protein HEMO, secreted form) in the extracellular medium.

Similarity. Belongs to the gamma type-C retroviral envelope protein family.

RefSeq proteins (2): NP_001229619, NP_078810 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018154	TLV/ENV_coat_polyprotein	Family

UniProt features (17 total): sequence conflict 5, mutagenesis site 4, chain 2, topological domain 2, glycosylation site 2, signal peptide 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9K5-F1	44.55	0.02

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 122, 192

Mutagenesis-validated functional residues (4):

Position	Phenotype
472–563	promotes release in the extracellular medium.
489–563	promotes release in the extracellular medium.
352–355	introduction of a furin cleavage site, promoting proteolytic cleavage of the protein by furin and release in the extrace
433–563	promotes release in the extracellular medium.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): MODULE_255, MODULE_317, MODULE_69, chr4q12, TOOKER_GEMCITABINE_RESISTANCE_UP, BILD_MYC_ONCOGENIC_SIGNATURE, MODULE_37, ZWANG_EGF_PERSISTENTLY_DN, MODULE_532, MIR938, MIR1288_5P, MANNO_MIDBRAIN_NEUROTYPES_HENDO, DESCARTES_FETAL_CEREBELLUM_VASCULAR_ENDOTHELIAL_CELLS, DESCARTES_FETAL_CEREBRUM_VASCULAR_ENDOTHELIAL_CELLS, ZNF680_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
membrane	1
cell periphery	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERVMER34-1	ERVV-1	B6SEH8	640
ERVMER34-1	ERVV-2	B6SEH9	622
ERVMER34-1	USP46	P62068	543
ERVMER34-1	OR2A2	Q6IF42	447
ERVMER34-1	A0A0U1RQV1	A0A0U1RQV1	431
ERVMER34-1	J3QSS9	J3QSS9	423
ERVMER34-1	MAPK1IP1L	Q8NDC0	407
ERVMER34-1	FREY1	C9JXX5	397
ERVMER34-1	ZNF782	Q6ZMW2	396
ERVMER34-1	A0A0B4J2G0	A0A0B4J2G0	396
ERVMER34-1	IVNS1ABP	Q9Y6Y0	394
ERVMER34-1	ZNF550	Q7Z398	394
ERVMER34-1	BLVRA	P53004	370
ERVMER34-1	STK10	O94804	355
ERVMER34-1	A0A2R8YDH4	A0A2R8YDH4	338

IntAct

11 interactions, top by confidence:

A	B	Type	Score
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
BTLA	MOCS3	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS)

ESM2 similar proteins: B6SEH8, B6SEH9, J7HBH4, O42043, O92955, P03380, P03381, P03383, P03396, P07575, P0C212, P0DTM4, P14075, P21412, P23064, P25057, P25504, P25505, P25506, P25507, P31789, P31796, P51519, P60507, P60508, P60509, P60608, P61550, P61552, P61553, P61554, P61555, P61556, P61557, P61558, P61561, P61562, P61563, P61564, Q03816

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

430 predictions. Top by Δscore:

Variant	Effect	Δscore
4:52750926:ATAC:A	donor_loss	0.9900
4:52750928:ACCT:A	donor_loss	0.9900
4:52751065:CTGCC:C	acceptor_gain	0.9900
4:52751070:C:CC	acceptor_gain	0.9900
4:52751341:A:AC	donor_gain	0.9900
4:52751342:C:CC	donor_gain	0.9900
4:52750929:CCTG:C	donor_gain	0.9800
4:52751066:TGCC:T	acceptor_gain	0.9800
4:52751068:CC:C	acceptor_gain	0.9800
4:52751069:CC:C	acceptor_gain	0.9800
4:52751069:CCTAG:C	acceptor_loss	0.9800
4:52751070:C:CA	acceptor_loss	0.9800
4:52751071:T:C	acceptor_loss	0.9800
4:52751342:CAGTG:C	donor_gain	0.9800
4:52751337:A:AC	donor_gain	0.9700
4:52751338:C:CC	donor_gain	0.9700
4:52751342:CA:C	donor_gain	0.9600
4:52751336:CACT:C	donor_loss	0.9300
4:52751339:T:TC	donor_loss	0.9300
4:52751340:C:CG	donor_loss	0.9300
4:52751341:ACA:A	donor_loss	0.9300
4:52751342:C:T	donor_loss	0.9300
4:52751337:ACTC:A	donor_loss	0.9200
4:52751067:GCC:G	acceptor_gain	0.9000
4:52751068:CCC:C	acceptor_gain	0.9000
4:52751338:CTCA:C	donor_gain	0.9000
4:52750928:A:AC	donor_gain	0.8800
4:52750929:C:CC	donor_gain	0.8800
4:52750949:TGCCG:T	donor_gain	0.8700
4:52751070:C:T	acceptor_gain	0.8600

AlphaMissense

3670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:52744582:C:A	W313C	0.972
4:52744582:C:G	W313C	0.972
4:52744571:C:G	C317S	0.962
4:52744572:A:T	C317S	0.962
4:52744627:A:C	F298L	0.962
4:52744627:A:T	F298L	0.962
4:52744629:A:G	F298L	0.962
4:52744572:A:G	C317R	0.951
4:52744584:A:G	W313R	0.951
4:52744584:A:T	W313R	0.951
4:52744741:C:A	W260C	0.951
4:52744741:C:G	W260C	0.951
4:52744619:C:G	C301S	0.949
4:52744620:A:T	C301S	0.949
4:52745386:C:A	W45C	0.942
4:52745386:C:G	W45C	0.942
4:52744023:A:G	C500R	0.934
4:52744362:C:G	A387P	0.932
4:52744620:A:G	C301R	0.918
4:52744743:A:G	W260R	0.918
4:52744743:A:T	W260R	0.918
4:52744571:C:T	C317Y	0.916
4:52744619:C:T	C301Y	0.916
4:52745381:C:G	C47S	0.915
4:52745382:A:T	C47S	0.915
4:52744563:C:A	G320W	0.913
4:52744562:C:T	G320E	0.908
4:52744882:C:A	W213C	0.907
4:52744882:C:G	W213C	0.907
4:52744188:A:G	C445R	0.905

dbSNP variants (sampled 300 via entrez): RS1000698995 (4:52747185 C>A,T), RS1000843025 (4:52753125 T>A), RS1000851228 (4:52752350 C>A,T), RS1000922575 (4:52746906 A>G), RS1001356858 (4:52747214 G>C), RS1001591252 (4:52744146 G>A), RS1001938149 (4:52750088 T>C), RS1002368322 (4:52745807 C>T), RS1002440926 (4:52747183 C>CA), RS1002610659 (4:52751179 C>A,G,T), RS1002735597 (4:52745293 C>A,T), RS1002766761 (4:52745585 G>A,T), RS1003209088 (4:52748941 G>A), RS1003265063 (4:52742760 C>T), RS1003837691 (4:52748652 C>G)

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

6 associations (top):

Study	Trait	p-value
GCST003811_5	Response to citalopram or escitalopram and depression	8.000000e-07
GCST009545_4	Moderate or severe prolonged lymphopenia in dimethyl fumarate-treated relapsing-remitting multiple sclerosis	3.000000e-06
GCST010699_75	Brain morphology (min-P)	3.000000e-18
GCST010701_71	Cortical surface area (MOSTest)	2.000000e-09
GCST010702_63	Subcortical volume (MOSTest)	8.000000e-12
GCST010703_102	Brain morphology (MOSTest)	6.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	5
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Pioglitazone	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	increases expression	1
Copper	decreases expression, affects binding	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Mustard Gas	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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