ERVV-2

Summary

ERVV-2 (endogenous retrovirus group V member 2, envelope, HGNC:39051) is a protein-coding gene on chromosome 19q13.41, encoding Endogenous retrovirus group V member 2 Env polyprotein (B6SEH9).

Many different human endogenous retrovirus (HERV) families are expressed in normal placental tissue at high levels, suggesting that HERVs are functionally important in reproduction. This gene is part of an HERV provirus on human chromosome 19 that has inactivating mutations in the gag and pol genes. This envelope glycoprotein gene appears to have been selectively preserved. The gene’s protein product is expressed in the placenta and acts as a syncytin in Old World monkeys, but has lost the fusogenic activity in humans and other primate lineages.

Source: NCBI Gene 100271846 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001191055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:39051
Approved symbol	ERVV-2
Name	endogenous retrovirus group V member 2, envelope
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	ENVV2
Ensembl gene	ENSG00000268964
Ensembl biotype	protein_coding
Entrez	100271846

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000601417

RefSeq mRNA: 1 — MANE Select: NM_001191055 NM_001191055

CCDS: CCDS59420

Canonical transcript exons

ENST00000601417 — 2 exons

Exon	Start	End
ENSE00003113554	53044740	53044958
ENSE00003127731	53048867	53051680

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 77.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3231 / max 178.7771, expressed in 54 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177320	0.3231	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	77.37	gold quality
sural nerve	UBERON:0015488	40.02	gold quality
bone marrow cell	CL:0002092	39.97	gold quality
stromal cell of endometrium	CL:0002255	39.82	gold quality
cortex of kidney	UBERON:0001225	39.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.14	gold quality
leukocyte	CL:0000738	36.99	gold quality
monocyte	CL:0000576	36.85	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
muscle tissue	UBERON:0002385	35.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.38	gold quality
bone marrow	UBERON:0002371	34.83	gold quality
skeletal muscle tissue	UBERON:0001134	34.71	gold quality
kidney	UBERON:0002113	34.59	gold quality
smooth muscle tissue	UBERON:0001135	34.33	silver quality
granulocyte	CL:0000094	34.31	gold quality
calcaneal tendon	UBERON:0003701	34.01	gold quality
mucosa of transverse colon	UBERON:0004991	34.01	gold quality
metanephros cortex	UBERON:0010533	33.94	gold quality
cerebellar hemisphere	UBERON:0002245	32.80	gold quality
cerebellum	UBERON:0002037	32.71	gold quality
cerebellar cortex	UBERON:0002129	32.64	gold quality
liver	UBERON:0002107	32.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	32.07	gold quality
urinary bladder	UBERON:0001255	31.79	gold quality
adult mammalian kidney	UBERON:0000082	31.20	silver quality
gall bladder	UBERON:0002110	30.89	gold quality
blood	UBERON:0000178	30.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	295.42
E-ANND-3	yes	3.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting ERVV-2, 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-4534	99.99	66.58	1907
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-6854-3P	90.99	65.18	155

Cross-species orthologs

0 orthologs

Paralogs (7): ERV3-1 (ENSG00000213462), ERVMER34-1 (ENSG00000226887), ERVW-1 (ENSG00000242950), ERVFRD-1 (ENSG00000244476), ERVV-1 (ENSG00000269526), (ENSG00000293569), (ENSG00000293570)

Protein

Protein identifiers

Endogenous retrovirus group V member 2 Env polyprotein — B6SEH9 (reviewed: B6SEH9)

Alternative names: HERV-V_19q13.41 provirus ancestral Env polyprotein 2

All UniProt accessions (2): B6SEH9, M9QSX5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Expressed in placenta.

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

RefSeq proteins (1): NP_001177984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018154	TLV/ENV_coat_polyprotein	Family

Pfam: PF00429

UniProt features (8 total): topological domain 3, transmembrane region 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B6SEH9-F1	46.18	0.00

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 (1): 68

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 4 (showing top): ZFP91_TARGET_GENES, MIR370_3P, MIR6893_3P, chr19q13

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERVV-2	ERVMER34-1	Q9H9K5	622
ERVV-2	GCM1	Q9NP62	461
ERVV-2	C4orf51	C9J302	447
ERVV-2	ITIH4	Q14624	434
ERVV-2	EMB	Q6PCB8	394
ERVV-2	CGB5	P01233	368
ERVV-2	MFSD2A	Q8NA29	364
ERVV-2	CLPSL1	A2RUU4	356
ERVV-2	LPCAT1	Q8NF37	350
ERVV-2	IVNS1ABP	Q9Y6Y0	330
ERVV-2	LGALS14	Q8TCE9	325
ERVV-2	MATN4	O95460	322
ERVV-2	XAGE2	Q96GT9	321
ERVV-2	C17orf58	Q2M2W7	320
ERVV-2	ENPEP	Q07075	311
ERVV-2	ZNF114	Q8NC26	311

IntAct

0 interactions, top by confidence:

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: B6SEH8, B6SEH9, P03385, P03399, P04502, P21415, P21436, P31796, P51515, P60508, P61550, P61553, P61554, P61556, P61557, P61561, P61562, P61563, Q5G5D5, Q8BI41, Q9TTC0, P08360, P11261, P11268, P11370, P15073, P31794, P60509, P61555, P61558, P61564, Q9N2K0, Q9UQF0, P03381, P03383, P03384, P03386, P03387, P03388, P03389

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

348 predictions. Top by Δscore:

Variant	Effect	Δscore
19:53044956:CAGGT:C	donor_loss	1.0000
19:53044957:AGG:A	donor_loss	1.0000
19:53044959:GT:G	donor_loss	1.0000
19:53049019:A:AG	donor_gain	1.0000
19:53044956:CAG:C	donor_gain	0.9900
19:53044957:AG:A	donor_gain	0.9900
19:53044958:GG:G	donor_gain	0.9900
19:53044959:G:GG	donor_gain	0.9900
19:53048863:ACAG:A	acceptor_loss	0.9900
19:53048864:CAG:C	acceptor_loss	0.9900
19:53048865:A:AG	acceptor_gain	0.9900
19:53048865:A:T	acceptor_loss	0.9900
19:53048866:G:GA	acceptor_gain	0.9900
19:53048866:GCT:G	acceptor_gain	0.9900
19:53049023:G:GG	donor_gain	0.9900
19:53044954:TCCAG:T	donor_gain	0.9800
19:53044955:CCAG:C	donor_gain	0.9800
19:53044960:T:G	donor_loss	0.9700
19:53048866:GC:G	acceptor_gain	0.9600
19:53049012:TGAA:T	donor_gain	0.9600
19:53048857:A:AG	acceptor_gain	0.9500
19:53048858:C:G	acceptor_gain	0.9500
19:53048862:A:AG	acceptor_gain	0.9500
19:53048866:GCTAT:G	acceptor_gain	0.9500
19:53048866:GCTA:G	acceptor_gain	0.9400
19:53049435:G:GG	donor_gain	0.9300
19:53048863:A:G	acceptor_gain	0.9200
19:53049018:GA:G	donor_gain	0.9100
19:53049656:G:GT	donor_gain	0.9100
19:53049022:A:AG	donor_gain	0.9000

AlphaMissense

3501 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:53050018:T:G	F256C	0.999
19:53050137:T:A	C296S	0.998
19:53050138:G:C	C296S	0.998
19:53049809:G:C	W186C	0.997
19:53049809:G:T	W186C	0.997
19:53050018:T:C	F256S	0.997
19:53050137:T:C	C296R	0.997
19:53049833:G:C	W194C	0.996
19:53049833:G:T	W194C	0.996
19:53049947:G:C	W232C	0.996
19:53049947:G:T	W232C	0.996
19:53050023:T:A	C258S	0.995
19:53050024:G:C	C258S	0.995
19:53050139:T:G	C296W	0.995
19:53050017:T:C	F256L	0.994
19:53050019:T:A	F256L	0.994
19:53050019:T:G	F256L	0.994
19:53049968:G:C	W239C	0.993
19:53049968:G:T	W239C	0.993
19:53050023:T:C	C258R	0.992
19:53050024:G:A	C258Y	0.992
19:53050025:T:G	C258W	0.992
19:53050138:G:A	C296Y	0.992
19:53049386:G:C	W45C	0.991
19:53049386:G:T	W45C	0.991
19:53049747:T:A	C166S	0.991
19:53049748:G:C	C166S	0.991
19:53050107:T:A	C286S	0.991
19:53050108:G:C	C286S	0.991
19:53049746:G:C	W165C	0.990

dbSNP variants (sampled 300 via entrez): RS1000104028 (19:53043687 C>A,T), RS1000123653 (19:53051928 A>T), RS1000139136 (19:53046262 GAAAA>G,GAAA,GAAAAA), RS1000192117 (19:53046053 G>C), RS1000472542 (19:53047322 T>C,G), RS1000977469 (19:53047031 G>A,C), RS1001275387 (19:53044094 T>A,C,G), RS1002243854 (19:53043085 A>G), RS1002245863 (19:53048403 C>T), RS1002428652 (19:53049069 C>A,T), RS1002580805 (19:53044454 G>A,T), RS1002596979 (19:53048707 A>G), RS1002762933 (19:53050993 T>C), RS1002800551 (19:53044701 G>C), RS1002896270 (19:53045213 G>T)

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

0 associations (top):

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
ethyl-p-hydroxybenzoate	decreases expression	1
Triclosan	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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