CH25H: Cholesterol 25-Hydroxylase

Key enzyme in cholesterol metabolism and antiviral immunity

Gene Information Card

Symbol CH25H
Full Name Cholesterol 25-Hydroxylase
Gene Type Protein-coding
Chromosomal Location 10q23.31
NCBI Gene ID 9023 ncbi.nlm.nih.gov/gene/9023
Ensembl ID ENSG00000138135
UniProt ID O95992
OMIM ID 604551
HGNC ID 1907
Aliases CH25H, C25H, 25-HC, 25-hydroxycholesterol

Description

CH25H encodes cholesterol 25-hydroxylase, an enzyme that catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25-HC). 25-HC is a potent regulator of cholesterol homeostasis and a key mediator of interferon-induced antiviral responses. It inhibits viral entry by blocking membrane fusion and modulates immune signaling. CH25H is induced by type I and type II interferons and plays a role in innate immunity against enveloped viruses including SARS-CoV-2, HIV, and Zika virus.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Atherosclerosis 25-HC suppresses SREBP processing, reducing cholesterol synthesis and promoting foam cell formation PMID: 23934897
Viral infections (e.g., SARS-CoV-2, HIV, Zika) 25-HC blocks viral membrane fusion and entry; CH25H upregulation is interferon-dependent PMID: 23934897, 32345962
Inflammatory diseases 25-HC modulates IL-1β and NLRP3 inflammasome activation PMID: 27374331
Cancer (breast, prostate) Altered cholesterol metabolism via 25-HC affects cell proliferation and tumor microenvironment PMID: 29590007

Expression Profile

Tissue Expression
Tissue nTPM level
Liver 2.3 Low
Lung 1.8 Low
Spleen 4.5 Medium
Lymph node 6.1 Medium
Bone marrow 3.2 Low
Brain 0.5 Not detected
Cell Line Expression
Cell Line nTPM Notes
HEK293 0.8 Low baseline; induced by interferon
THP-1 (macrophage) 12.5 High after LPS/IFN-γ stimulation
HepG2 1.1 Low
A549 (lung) 2.3 Inducible by interferon
Jurkat (T-cell) 0.6 Not detected
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1A>G (p.Met1?) Missense <0.01% Likely loss of start codon; functional impact unknown
c.352C>T (p.Arg118Cys) Missense <0.01% Reduced enzymatic activity in vitro
c.500G>A (p.Arg167His) Missense <0.01% Unknown
Mutation functional classification

Loss of Function (LOF)

p.Arg118Cys reduces 25-HC production; p.Met1? abolishes translation

Gain of Function (GOF)

No gain-of-function mutations reported

Dominant Negative (DN)

Not described

Pathways

• Cholesterol metabolism (Reactome: R-HSA-191273)
• Interferon signaling (Reactome: R-HSA-913531)
• SREBP signaling (Reactome: R-HSA-1655829)
• Innate immune system (Reactome: R-HSA-168249)

Protein Summary

Cholesterol 25-hydroxylase is a 272-amino-acid endoplasmic reticulum membrane protein that converts cholesterol to 25-hydroxycholesterol. 25-HC acts as a feedback regulator of cholesterol synthesis by inhibiting SREBP processing and activating LXR signaling. It also exerts broad antiviral activity by blocking viral membrane fusion. The enzyme is highly induced by interferons and is a critical component of the interferon antiviral response.

Related Products

Product name Cat.No. Species Gene ID
CH25H Knockout HEK293 Cell Line EDJ-KQ6432 Human 9023 Details Get a Quote
CH25H Knockout HeLa Cell Line EDJ-KQ55056 Human 9023 Details Get a Quote
CH25H Knockout A-549 Cell Line EDJ-KQ63537 Human 9023 Details Get a Quote
CH25H Knockout HCT 116 Cell Line EDJ-KQ72007 Human 9023 Details Get a Quote
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