HSERVPRODH

Chr 22

human-specific endogenous retroviral insert PRODH enhancer

Also known as: hsERV_PRODH

This region includes an endogenous retrovirus long-terminal repeat (LTR)-derived sequence that binds SRY (sex determining region Y)-box 2 (SOX2) and functions as an enhancer of the proline dehydrogenase (oxidase) 1 (PRODH) gene in Tera-1 (testicular embryonal germ cell tumor) cells. The LTR sequence acts synergistically with a CG-rich region downstream of the transcription start site to promote expression of the PRODH gene. Cytosine methylation of the LTR element but not the CG-region can prevent enhancer activity. The orthologous sequence in chimpanzee does not function as an enhancer, suggesting that regulation by this region is human-specific. A subregion of the LTR element was also validated as a functional enhancer by Sharpr-MPRA (Systematic high-resolution activation and repression profiling with reporter tiling using massively parallel reporter assays) in HepG2 liver carcinoma cells (group: HepG2 Activating non-DNase unmatched - State 3:PromF, promoter flanking), but the same subregion displayed repressive activity by Sharpr-MPRA in K562 erythroleukemia cells (group: K562 Repressive non-DNase unmatched - State 22:ReprW, weaker Polycomb repression). A subregion was also shown to be an enhancer by the ChIP-STARR-seq massively parallel reporter assay in naive human embryonic stem cells, where it associates with the OCT4 and NANOG transcription factors and is marked by the H3K27ac histone modification. [provided by RefSeq, Dec 2022]

202
ClinVar variants
175
Pathogenic / LP
pLI score
0
Active trials
Clinical SummaryHSERVPRODH
📋
ClinVar Variants
175 Pathogenic / Likely Pathogenic· 14 VUS of 202 total submissions
Some data sources returned errors (2)

ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/HSERVPRODH?content-type=application/json&expand=1

gnomad: Error: Gene not found

Population Genetics & Constraint

Constraint data not available from gnomAD.

ClinVar Variant Classifications

202 submitted variants in ClinVar

Classification Summary

Pathogenic173
Likely Pathogenic2
VUS14
Likely Benign9
Benign2
173
Pathogenic
2
Likely Pathogenic
14
VUS
9
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
173
Likely Pathogenic
2
VUS
14
Likely Benign
9
Benign
2
Total200

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HSERVPRODH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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