HFM1 Gene - ATP-Dependent DNA Helicase in Meiotic Recombination
Essential for homologous recombination and fertility; mutations linked to premature ovarian failure and azoospermia
Gene Information Card
| Symbol | HFM1 |
|---|---|
| Full Name | HFM1, ATP-dependent DNA helicase homolog (S. cerevisiae) |
| Gene Type | Protein coding |
| Chromosomal Location | 1p22.2 |
| NCBI Gene ID | 164045 ncbi.nlm.nih.gov/gene/164045 |
| Ensembl ID | ENSG00000162669 |
| UniProt ID | Q8IZ73 |
| OMIM ID | 615684 |
| HGNC ID | 20193 |
| Aliases | MER3, SEC63D2, FLJ12747, bA467N20.1 |
Description
HFM1 (also known as MER3) encodes an ATP-dependent DNA helicase that plays a critical role in meiotic homologous recombination. The protein is essential for crossover formation and chromosome synapsis during meiosis I. Mutations in HFM1 are associated with premature ovarian failure 9 (POF9) and non-obstructive azoospermia, highlighting its importance in human fertility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Premature ovarian failure 9 (POF9) | Loss-of-function mutations impair meiotic recombination, leading to ovarian dysfunction and early menopause | OMIM #615684; ClinVar |
| Non-obstructive azoospermia | Defective meiotic progression due to HFM1 deficiency results in spermatogenic arrest | ClinVar; literature reports |
| Primary ovarian insufficiency | Homozygous and compound heterozygous variants disrupt helicase activity, causing follicular depletion | OMIM; NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Ovary | 6.8 | Low |
| Fallopian tube | 4.2 | Low |
| Thyroid | 2.1 | Not detected |
| Adrenal gland | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 0.3 | Not detected |
| K562 | 0.1 | Not detected |
| HepG2 | 0.2 | Not detected |
| Testis (Sertoli cells) | 8.9 | Low |
| Ovarian granulosa cells | 5.4 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2939G>A (p.Arg980His) | Missense | Rare | Loss of helicase activity; associated with POF9 |
| c.1681C>T (p.Arg561*) | Nonsense | Rare | Premature truncation; loss of function in azoospermia |
| c.415_416del (p.Gln139Valfs*2) | Frameshift | Rare | Null allele; homozygous in POF9 families |
| c.1972G>A (p.Gly658Arg) | Missense | Rare | Impaired ATP binding; reduced recombination |
Mutation functional classification
Loss of Function (LOF)
Most HFM1 mutations are loss-of-function, leading to defective meiotic recombination and infertility.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • helicase activity (GO:0004386) | • ATP binding (GO:0005524) |
| • reciprocal meiotic recombination (GO:0007131) | • synapsis (GO:0007129) |
| • nucleus (GO:0005634) | • DNA helicase activity (GO:0003678) |
Pathways
• Meiotic recombination (Reactome: R-HSA-912446)
• Homologous recombination (KEGG: hsa03440)
Protein Summary
HFM1 is a 1,238-amino acid ATP-dependent DNA helicase belonging to the DEAH-box helicase family. It localizes to the nucleus and is specifically expressed in germ cells. The protein promotes meiotic crossover formation by unwinding DNA and facilitating strand exchange. Structural domains include a helicase ATP-binding domain and a helicase C-terminal domain. Mutations disrupting these domains cause meiotic arrest and infertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HFM1 Knockout HEK293 Cell Line | EDJ-KQ13745 | Human | 164045 | Details Get a Quote |
| HFM1 Knockout HeLa Cell Line | EDJ-KQ58868 | Human | 164045 | Details Get a Quote |
| HFM1 Knockout A-549 Cell Line | EDJ-KQ67359 | Human | 164045 | Details Get a Quote |
| HFM1 Knockout HCT 116 Cell Line | EDJ-KQ75752 | Human | 164045 | Details Get a Quote |
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