HENMT1: HEN Methyltransferase 1
A piRNA pathway methyltransferase essential for male fertility
Gene Information Card
| Symbol | HENMT1 |
|---|---|
| Full Name | HEN Methyltransferase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 113802 ncbi.nlm.nih.gov/gene/113802 |
| Ensembl ID | ENSG00000162669 |
| UniProt ID | Q5T8I9 |
| OMIM ID | 611111 |
| HGNC ID | 25258 |
| Aliases | HEN1, HEN1 methyltransferase, piRNA methyltransferase |
Description
HENMT1 (HEN Methyltransferase 1) encodes a methyltransferase that catalyzes the 2'-O-methylation of the 3' end of PIWI-interacting RNAs (piRNAs). This modification is critical for piRNA stability and function in the germline, particularly during spermatogenesis. HENMT1 is predominantly expressed in testis and is essential for male fertility. Loss-of-function mutations in HENMT1 cause non-obstructive azoospermia and spermatogenic failure.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spermatogenic failure 81 | Loss of HENMT1 disrupts piRNA 2'-O-methylation, leading to piRNA instability and defective transposon silencing in germ cells, resulting in meiotic arrest and azoospermia. | OMIM #620277; ClinVar; PMID: 31630787 |
| Non-obstructive azoospermia | Homozygous frameshift or nonsense mutations in HENMT1 cause complete absence of sperm due to spermatogenic arrest. | ClinVar; PMID: 31630787 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 20.1 | High |
| Brain | 0.3 | Low |
| Heart | 0.1 | Not detected |
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Seminoma cell line (TCam-2) | 15.4 | Testicular germ cell tumor model |
| HEK293 | 0.2 | Low expression |
| HeLa | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.430_431del (p.Leu144Glufs*2) | Frameshift | Rare | Loss of function; causes spermatogenic failure |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein produced |
| c.556C>T (p.Arg186*) | Nonsense | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
All reported pathogenic mutations in HENMT1 are loss-of-function (frameshift, nonsense, start loss), leading to absent or non-functional methyltransferase and defective piRNA modification.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HENMT1.
Dominant Negative (DN)
No dominant-negative mutations have been described for HENMT1.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • RNA methyltransferase activity (GO:0008173) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
| • piRNA processing (GO:0034587) | • piRNA 2'-O-methylation (GO:0034588) |
| • spermatogenesis (GO:0007283) | • RNA metabolic process (GO:0016070) |
Pathways
• piRNA biogenesis and function (Reactome: R-HSA-5601884)
• Meiotic recombination (Reactome: R-HSA-912446)
Protein Summary
HENMT1 is a 476-amino acid methyltransferase that specifically modifies the 3' terminal nucleotide of piRNAs by adding a 2'-O-methyl group. This modification protects piRNAs from degradation and is essential for their role in silencing transposable elements in the germline. The protein contains a conserved methyltransferase domain and localizes to both the nucleus and cytoplasm of spermatogenic cells. HENMT1 is highly expressed in testis and is required for normal meiotic progression during spermatogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HENMT1 Knockout HEK293 Cell Line | EDJ-KQ2560 | Human | 113802 | Details Get a Quote |
| HENMT1 Knockout A-549 Cell Line | EDJ-KQ23223 | Human | 113802 | Details Get a Quote |
| HENMT1 Knockout HeLa Cell Line | EDJ-KQ23224 | Human | 113802 | Details Get a Quote |
| HENMT1 Knockout HCT 116 Cell Line | EDJ-KQ74830 | Human | 113802 | Details Get a Quote |
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