ERV3-1

Summary

ERV3-1 (endogenous retrovirus group 3 member 1, envelope, HGNC:3454) is a protein-coding gene on chromosome 7q11.21, encoding Endogenous retrovirus group 3 member 1 Env polyprotein (Q14264). Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection.

This gene contains sequence derived from endogenous retrovirus, and is therefore similar to multiple other loci in the genome. Transcripts at this locus encode a conserved protein with a predicted signal peptide and similarity to the Env polyprotein. This protein is overexpressed in colorectal and other cancers.

Source: NCBI Gene 2086 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_001007253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3454
Approved symbol	ERV3-1
Name	endogenous retrovirus group 3 member 1, envelope
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Aliases	H-PLK, HERV-R, ERV-R, envR
Ensembl gene	ENSG00000213462
Ensembl biotype	protein_coding
OMIM	131170
Entrez	2086

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000394323, ENST00000528878, ENST00000535538

RefSeq mRNA: 2 — MANE Select: NM_001007253 NM_001007253, NM_001396062

CCDS: CCDS47595

Canonical transcript exons

ENST00000394323 — 2 exons

Exon	Start	End
ENSE00001524822	64990356	64993414
ENSE00001769323	65006541	65006687

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3094 / max 236.1517, expressed in 1449 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84203	20.7058	1751
84202	4.7621	1110
84204	1.5472	895

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.49	gold quality
right adrenal gland cortex	UBERON:0035827	92.40	gold quality
left adrenal gland	UBERON:0001234	92.28	gold quality
left adrenal gland cortex	UBERON:0035825	92.20	gold quality
right adrenal gland	UBERON:0001233	91.71	gold quality
lower esophagus mucosa	UBERON:0035834	90.44	gold quality
monocyte	CL:0000576	89.73	gold quality
adrenal gland	UBERON:0002369	89.66	gold quality
leukocyte	CL:0000738	89.15	gold quality
adrenal cortex	UBERON:0001235	88.65	gold quality
gall bladder	UBERON:0002110	88.53	gold quality
omental fat pad	UBERON:0010414	86.80	gold quality
peritoneum	UBERON:0002358	86.67	gold quality
cortical plate	UBERON:0005343	86.31	gold quality
ganglionic eminence	UBERON:0004023	86.07	gold quality
islet of Langerhans	UBERON:0000006	85.93	gold quality
right lung	UBERON:0002167	85.71	gold quality
minor salivary gland	UBERON:0001830	85.50	gold quality
esophagus mucosa	UBERON:0002469	85.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.87	gold quality
calcaneal tendon	UBERON:0003701	84.53	gold quality
vermiform appendix	UBERON:0001154	84.30	gold quality
right uterine tube	UBERON:0001302	84.14	gold quality
left coronary artery	UBERON:0001626	83.89	gold quality
bone marrow cell	CL:0002092	83.66	gold quality
skin of abdomen	UBERON:0001416	83.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.31	gold quality
granulocyte	CL:0000094	82.83	gold quality
left ovary	UBERON:0002119	82.75	gold quality
left testis	UBERON:0004533	82.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting ERV3-1, 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-4692	100.00	67.32	2066
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-200C-5P	97.71	67.73	596

Literature-anchored findings (GeneRIF, showing 5)

• molecular evolution and comparison with other primates (PMID:15081124)
• Letter: report elevated ERV3-1 levels in colorectal neoplasms. (PMID:25016529)
• ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. (PMID:26992684)
• Expression of ERV3-1 in leukocytes of acute myelogenous leukemia patients. (PMID:33338509)
• Endogenous Retrovirus RNA Expression Differences between Race, Stage and HPV Status Offer Improved Prognostication among Women with Cervical Cancer. (PMID:36675007)

Cross-species orthologs

0 orthologs

Paralogs (7): ERVMER34-1 (ENSG00000226887), ERVW-1 (ENSG00000242950), ERVFRD-1 (ENSG00000244476), ERVV-2 (ENSG00000268964), ERVV-1 (ENSG00000269526), (ENSG00000293569), (ENSG00000293570)

Protein

Protein identifiers

Endogenous retrovirus group 3 member 1 Env polyprotein — Q14264 (reviewed: Q14264)

Alternative names: ERV-3 envelope protein, ERV3-1 envelope protein, Envelope polyprotein, HERV-R envelope protein, HERV-R_7q21.2 provirus ancestral Env polyprotein

All UniProt accessions (1): Q14264

UniProt curated annotations — full annotation on UniProt →

Function. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution. This endogenous envelope protein has lost its fusogenic properties. It can inhibit cell growth through decrease expression of cyclin B1 and increased expression of p21 in vitro. SU mediates receptor recognition. TM anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane.

Subunit / interactions. The surface (SU) and transmembrane (TM) proteins form a heterodimer. SU and TM are attached by non-covalent interactions or by a labile interchain disulfide bond.

Subcellular location. Virion.

Tissue specificity. Expressed at higher level in adrenal, sebaceous glands and placenta. Expressed at lower level in bone marrow, brain, breast, colon, heart, kidney, liver, lung, ovary, PBL, prostate, skin, spleen, testis, thymus, thyroid, trachea.

Post-translational modifications. Specific enzymatic cleavages in vivo yield the mature SU and TM proteins. Has been mainly detected in vivo as an 65 kDa unprocessed polyprotein precursor. The CXXC motif is highly conserved across a broad range of retroviral envelope proteins. It is thought to participate in the formation of a labile disulfide bond possibly with the CX6CC motif present in the transmembrane protein. Isomerization of the intersubunit disulfide bond to an SU intrachain disulfide bond is thought to occur upon receptor recognition in order to allow membrane fusion.

Domain organisation. Contains the CKS-17 immunosuppressive domain present in many retroviral envelope proteins. As a synthetic peptide, it inhibits immune function in vitro and in vivo.

Polymorphism. This envelope gene is polymorphic with at least five different alleles. A mutation introducing a premature stop codon instead of amino acid 223 is present in approximately 1% of the Caucasian population.

Miscellaneous. HERV-R_7q21.2 genomic and subgenomic RNAs have been observed. This provirus is intergenic, the closest flanking genes being ZNF117 and FLJ25037.

Similarity. Belongs to the gamma type-C retroviral envelope protein family. HERV class-I R env subfamily.

RefSeq proteins (2): NP_001007254, NP_001382991 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018154	TLV/ENV_coat_polyprotein	Family

UniProt features (26 total): glycosylation site 9, sequence variant 6, chain 3, sequence conflict 3, short sequence motif 3, signal peptide 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14264-F1	66.48	0.04

Functional residue map

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

Catalytic / active sites (1): 471–472 (cleavage)

Glycosylation sites (9): 201, 316, 369, 382, 399, 527, 569, 64, 105

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): GCM_PRKCG, GCM_RING1, chr7q11, GCM_CDH5, GCM_FANCC, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, PEDRIOLI_MIR31_TARGETS_DN, GCM_HMGA2, ARID5B_TARGET_GENES, ASH1L_TARGET_GENES, CREB3L4_TARGET_GENES, HOXC13_TARGET_GENES, ID2_TARGET_GENES, NKX2_2_TARGET_GENES, UBN1_TARGET_GENES

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (1): molecular_function (GO:0003674)

GO Cellular Component (0):

Protein interactions and networks

STRING

2686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERV3-1	ACE2	Q9BYF1	992
ERV3-1	PLG	P00747	977
ERV3-1	FN1	P02751	954
ERV3-1	CFH	P08603	938
ERV3-1	CDH1	P12830	929
ERV3-1	ALB	P02768	866
ERV3-1	ATAD1	Q8NBU5	797
ERV3-1	SLC10A1	Q14973	792
ERV3-1	CD4	P01730	760
ERV3-1	C3	P01024	745
ERV3-1	TLR4	O00206	741
ERV3-1	LTF	P02788	718
ERV3-1	GYPA	P02724	718
ERV3-1	X6REF7	X6REF7	697
ERV3-1	ANXA2	P07355	690

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TRAF3IP1	ERV3-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): ERV3-1 (Affinity Capture-RNA), ERV3-1 (Affinity Capture-MS), ERV3-1 (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

Diamond homologs: O11458, P0C770, P0C771, P0C772, P0C773, P35253, P35254, P60170, P60171, P60172, P60173, P60507, P87666, P87670, P87671, Q14264, Q1PD50, Q1PDC7, Q66799, Q66800, Q66810, Q66811, Q6UY66, Q7T9E0, Q89569, Q89853, Q8MIB6, Q91DD7, Q91DD8, Q9YMG2, O11457, Q05320, Q66798, Q66814, Q7T9D9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

9 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	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

386 predictions. Top by Δscore:

Variant	Effect	Δscore
7:65006537:TCAC:T	donor_loss	1.0000
7:65006539:ACCAT:A	donor_loss	1.0000
7:65006537:T:A	donor_gain	0.9900
7:65006539:A:AC	donor_gain	0.9900
7:65006540:C:CC	donor_gain	0.9900
7:65006553:T:TA	donor_gain	0.9900
7:64993416:T:C	acceptor_gain	0.9800
7:65006539:AC:A	donor_gain	0.9800
7:65006540:CC:C	donor_gain	0.9800
7:64993415:C:CC	acceptor_gain	0.9700
7:65006540:CCA:C	donor_gain	0.9700
7:65006575:G:C	donor_gain	0.9700
7:64990765:ATC:A	donor_gain	0.9600
7:64993412:CAA:C	acceptor_gain	0.9600
7:64993414:ACT:A	acceptor_loss	0.9600
7:64993415:C:A	acceptor_loss	0.9600
7:64990976:A:AC	donor_gain	0.9500
7:64990977:C:CC	donor_gain	0.9500
7:64990979:T:TA	donor_gain	0.9500
7:64990767:C:A	donor_gain	0.9400
7:64993422:A:T	acceptor_gain	0.9300
7:64990967:T:C	donor_gain	0.9200
7:64990970:T:TA	donor_gain	0.9200
7:64991020:A:AC	donor_gain	0.9100
7:64993417:T:TC	acceptor_gain	0.9100
7:64993425:A:T	acceptor_gain	0.9100
7:65006189:T:TA	donor_gain	0.9000
7:65006190:C:A	donor_gain	0.9000
7:64993417:T:C	acceptor_gain	0.8900
7:65006540:CCAT:C	donor_gain	0.8900

AlphaMissense

3924 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:64991709:C:A	G440W	0.993
7:64991728:C:A	W433C	0.991
7:64991728:C:G	W433C	0.991
7:64991770:C:A	W419C	0.989
7:64991770:C:G	W419C	0.989
7:64991730:A:G	W433R	0.986
7:64991730:A:T	W433R	0.986
7:64991968:A:C	F353L	0.986
7:64991968:A:T	F353L	0.986
7:64991970:A:G	F353L	0.986
7:64991536:C:A	W497C	0.985
7:64991536:C:G	W497C	0.985
7:64991580:A:G	W483R	0.985
7:64991580:A:T	W483R	0.985
7:64991578:C:A	W483C	0.983
7:64991578:C:G	W483C	0.983
7:64992109:C:A	W306C	0.982
7:64992109:C:G	W306C	0.982
7:64991794:C:A	W411C	0.981
7:64991794:C:G	W411C	0.981
7:64991765:C:G	C421S	0.980
7:64991766:A:T	C421S	0.980
7:64991538:A:G	W497R	0.979
7:64991538:A:T	W497R	0.979
7:64991765:C:T	C421Y	0.979
7:64992391:C:A	W212C	0.979
7:64992391:C:G	W212C	0.979
7:64991772:A:G	W419R	0.977
7:64991772:A:T	W419R	0.977
7:64992020:A:G	L336S	0.977

dbSNP variants (sampled 300 via entrez): RS1000100520 (7:64999584 A>C,G), RS1000209557 (7:64996481 T>C), RS1000269361 (7:65001796 AAC>A), RS1000315821 (7:64989997 G>A,C), RS1000366499 (7:64990290 C>A,T), RS1000407673 (7:65007552 A>G), RS1000628260 (7:65003530 A>C,G), RS1000699567 (7:64991348 T>A,C), RS1000722513 (7:65002048 C>A), RS1000743195 (7:65008570 T>C), RS1001158016 (7:64997879 G>T), RS1001684954 (7:65002650 T>C), RS1001749018 (7:65002472 T>C), RS1002000551 (7:64998047 C>G,T), RS1002086157 (7:65003783 A>C,G)

Disease associations

OMIM: gene MIM:131170 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Ethanol	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Folic Acid	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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