Details for: HFM1

Gene ID: 164045

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HFM1

Ensembl ID: ENSG00000162669

Description: helicase for meiosis 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • vascular leptomeningeal cell CL4023051
    CSI 11.87
    rCSI 20.81%
    PRS 93.09
  • cerebral cortex endothelial cell CL1001602
    CSI 8.65
    rCSI 14.97%
    PRS 91.81
  • melanocyte CL0000148
    CSI 7.68
    rCSI 5.69%
    PRS 92.74
  • amacrine cell CL0000561
    CSI 5.62
    rCSI 16.3%
    PRS 89.09
  • glutamatergic neuron CL0000679
    CSI 5.54
    rCSI 11.39%
    PRS 86.12
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 5.49
    rCSI 13.13%
    PRS 87.6
  • retinal ganglion cell CL0000740
    CSI 5.01
    rCSI 11.06%
    PRS 87.78
  • podocyte CL0000653
    CSI 4.93
    rCSI 21.92%
    PRS 94.82
  • GABAergic neuron CL0000617
    CSI 4.32
    rCSI 14.47%
    PRS 84.99
  • rod bipolar cell CL0000751
    CSI 3.69
    rCSI 6.63%
    PRS 91.34
  • inhibitory interneuron CL0000498
    CSI 3.63
    rCSI 8.37%
    PRS 88.75
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.58
    rCSI 4.13%
    PRS 89.26
  • retinal bipolar neuron CL0000748
    CSI 3.44
    rCSI 6.44%
    PRS 89.36
  • cerebellar granule cell CL0001031
    CSI 3.33
    rCSI 4.9%
    PRS 91.56
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.17
    rCSI 4.09%
    PRS 87.51
  • neural crest cell CL0011012
    CSI 3.12
    rCSI 2.47%
    PRS 90.68
  • interneuron CL0000099
    CSI 2.91
    rCSI 5.84%
    PRS 91.28
  • hepatic stellate cell CL0000632
    CSI 2.82
    rCSI 10.57%
    PRS 92.55
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.78
    rCSI 4.66%
    PRS 86.69
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.77
    rCSI 3.45%
    PRS 84.59
  • adipocyte CL0000136
    CSI 2.67
    rCSI 3.42%
    PRS 89.06
  • glioblast CL0000030
    CSI 2.61
    rCSI 4.16%
    PRS 89.39
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.58
    rCSI 6.55%
    PRS 91.46
  • regulatory T cell CL0000815
    CSI 2.53
    rCSI 2.93%
    PRS 88.73
  • retinal rod cell CL0000604
    CSI 2.52
    rCSI 4.45%
    PRS 91.87
  • retinal pigment epithelial cell CL0002586
    CSI 2.44
    rCSI 4.85%
    PRS 92.51
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.43
    rCSI 4.42%
    PRS 90.85
  • Mueller cell CL0000636
    CSI 2.32
    rCSI 5.3%
    PRS 90.66
  • macroglial cell CL0000126
    CSI 2.29
    rCSI 5.9%
    PRS 91.78
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.26
    rCSI 5.48%
    PRS 84.74
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.19
    rCSI 4.9%
    PRS 86.74
  • Bergmann glial cell CL0000644
    CSI 2.04
    rCSI 2.79%
    PRS 89.62
  • ependymal cell CL0000065
    CSI 1.93
    rCSI 3.92%
    PRS 81.35
  • neural cell CL0002319
    CSI 1.87
    rCSI 7.04%
    PRS 84.48
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.77
    rCSI 11.04%
    PRS 90.24
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.76
    rCSI 2.1%
    PRS 86.58
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.68
    rCSI 2.7%
    PRS 87.49
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.65
    rCSI 2.91%
    PRS 86.06
  • invaginating midget bipolar cell CL4033034
    CSI 1.58
    rCSI 9.35%
    PRS 87.49
  • parietal epithelial cell CL1000452
    CSI 1.58
    rCSI 4.23%
    PRS 91.73
  • microglial cell CL0000129
    CSI 1.57
    rCSI 6.33%
    PRS 93.71
  • cardiac muscle cell CL0000746
    CSI 1.49
    rCSI 2.14%
    PRS 89.04
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.36
    rCSI 4.26%
    PRS 87.54
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.24
    rCSI 4.71%
    PRS 86.76
  • H2 horizontal cell CL0004218
    CSI 1.23
    rCSI 6.13%
    PRS 90.79
  • diffuse bipolar 6 cell CL4033032
    CSI 1.22
    rCSI 6.41%
    PRS 86.85
  • regular atrial cardiac myocyte CL0002129
    CSI 1.16
    rCSI 3.74%
    PRS 91.93
  • glial cell CL0000125
    CSI 0.96
    rCSI 3.64%
    PRS 90.13
  • diffuse bipolar 2 cell CL4033028
    CSI 0.96
    rCSI 7.4%
    PRS 88.56
  • diffuse bipolar 1 cell CL4033027
    CSI 0.91
    rCSI 6.85%
    PRS 85.64
  • OFF midget ganglion cell CL4033047
    CSI 0.91
    rCSI 18.44%
    PRS 88.87
  • diffuse bipolar 3b cell CL4033030
    CSI 0.9
    rCSI 5.95%
    PRS 89.65
  • flat midget bipolar cell CL4033033
    CSI 0.87
    rCSI 6.22%
    PRS 87.04
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.76
    rCSI 2.75%
    PRS 85.08
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.75
    rCSI 4.44%
    PRS 87.05
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.75
    rCSI 2.33%
    PRS 88.94
  • diffuse bipolar 3a cell CL4033029
    CSI 0.72
    rCSI 4.91%
    PRS 87.99
  • ON parasol ganglion cell CL4033052
    CSI 0.71
    rCSI 10.02%
    PRS 89.15
  • starburst amacrine cell CL0004232
    CSI 0.69
    rCSI 5.78%
    PRS 83.46
  • central nervous system neuron CL2000029
    CSI 0.64
    rCSI 4.71%
    PRS 89.76
  • ON midget ganglion cell CL4033046
    CSI 0.64
    rCSI 13.03%
    PRS 88.42
  • blood vessel smooth muscle cell CL0019018
    CSI 0.63
    rCSI 5.16%
    PRS 93.95
  • medium spiny neuron CL1001474
    CSI 0.32
    rCSI 2.74%
    PRS 89.44

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HFM1](/details-gene/164045) (Helicase for Meiosis 1) is a protein-coding gene located on chromosome 1p22.2, which encodes a putative ATP-dependent DNA helicase. Functionally, it is annotated with roles in [Dna duplex unwinding (GO:0032508)](https://www.ebi.ac.uk/QuickGO/term/GO:0032508) and is implicated in the resolution of meiotic recombination intermediates, a critical step for ensuring genomic integrity during gamete formation ([Link](https://doi.org/10.1080/10425170600805433)). Loss-of-function mutations in [HFM1](/details-gene/164045) have been linked to recessive primary ovarian insufficiency ([Link](https://doi.org/10.1056/nejmc1310150)). Despite its well-characterized role in meiosis, broad expression data suggests its highest significance is not in germline cells but rather in a diverse set of somatic cell types, particularly within the central nervous system vasculature and neuronal populations. ## Cellular Roles and Expression Landscape The expression profile of [HFM1](/details-gene/164045) presents a notable divergence from its established meiotic function. **Overall**, the gene exhibits the highest significance in cell types associated with the central nervous system (CNS) and its supporting vasculature. The most significant expression is observed in [vascular leptomeningeal cell](/details-cell/CL4023051) (CSI: 11.87) and [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 8.65), suggesting a potentially important role in the maintenance or function of the blood-brain barrier and associated meningeal structures. A high CSI is also found in [melanocyte](/details-cell/CL0000148) (CSI: 7.68), indicating a significant, though less understood, function in this cell type. Furthermore, [HFM1](/details-gene/164045) is a significant marker across a wide array of neuronal subtypes. These include [amacrine cell](/details-cell/CL0000561) (CSI: 5.62), [glutamatergic neuron](/details-cell/CL0000679) (CSI: 5.54), [retinal ganglion cell](/details-cell/CL0000740) (CSI: 5.01), and [GABAergic neuron](/details-cell/CL0000617) (CSI: 4.32). This broad but significant expression pattern across different neuronal classes suggests a general role in neuronal biology, possibly related to the maintenance of genomic integrity in these long-lived, post-mitotic cells. Other cell types with notable significance include renal [podocyte](/details-cell/CL0000653) (CSI: 4.93). The consistent high significance in these specialized, terminally differentiated cells suggests that the DNA helicase activity of [HFM1](/details-gene/164045) may be co-opted for functions beyond meiosis, such as DNA repair or transcriptional regulation. ## Pathways and Molecular Function The molecular functions attributed to [HFM1](/details-gene/164045) are centered on its identity as a DNA helicase. It is associated with [Atp binding (GO:0005524)](https://www.ebi.ac.uk/QuickGO/term/GO:0005524), [Atp hydrolysis activity (GO:0016887)](https://www.ebi.ac.uk/QuickGO/term/GO:0016887), and [Dna helicase activity (GO:0003678)](https://www.ebi.ac.uk/QuickGO/term/GO:0003678), all of which are essential for its primary role in unwinding DNA duplexes. This activity is a prerequisite for its involvement in the biological process of [Resolution of meiotic recombination intermediates (GO:0000712)](https://www.ebi.ac.uk/QuickGO/term/GO:0000712). Consistent with these nuclear processes, its protein product is primarily localized to the [Nucleus (GO:0005634)](https://www.ebi.ac.uk/QuickGO/term/GO:0005634). While these functions are well-established in the context of meiosis, they are also fundamental to other DNA-dependent processes like DNA repair, replication, and transcription, which could explain its high significance in metabolically active and long-lived somatic cells like neurons and endothelial cells. ## Research Directions The disparity between the established meiotic function of [HFM1](/details-gene/164045) and its observed expression profile in somatic tissues, particularly the CNS, opens several avenues for future investigation. ### Testable Hypotheses 1. **Hypothesis:** [HFM1](/details-gene/164045) plays a critical role in maintaining the integrity of the blood-brain barrier by supporting DNA repair mechanisms in the specialized [cerebral cortex endothelial cell](/details-cell/CL1001602), which are exposed to hemodynamic stress and potential genotoxic agents. 2. **Hypothesis:** In long-lived, post-mitotic cells such as the [glutamatergic neuron](/details-cell/CL0000679), [HFM1](/details-gene/164045) functions as a key component of the DNA damage response pathway, helping to prevent the accumulation of mutations over an organism's lifespan. 3. **Hypothesis:** The high significance of [HFM1](/details-gene/164045) in [melanocyte](/details-cell/CL0000148) suggests its involvement in the repair of UV-induced DNA damage, a critical process for preventing melanomagenesis. ### Proposed Experiment To test the hypothesis that [HFM1](/details-gene/164045) is crucial for blood-brain barrier integrity, an *in vitro* model using primary human cerebral microvascular endothelial cells could be employed. [HFM1](/details-gene/164045) expression could be silenced using CRISPR interference (CRISPRi). The impact of its knockdown on barrier function would be assessed by measuring transendothelial electrical resistance (TEER). Furthermore, cells would be challenged with a DNA-damaging agent (e.g., hydrogen peroxide or ionizing radiation), and the efficiency of DNA repair could be quantified by immunofluorescence staining for damage markers like gamma-H2AX foci. A significant decrease in TEER and an increase in persistent gamma-H2AX foci in knockdown cells would support this hypothesis. ### Therapeutic Potential Given that loss-of-function mutations in [HFM1](/details-gene/164045) are causative for primary ovarian insufficiency ([Link](https://doi.org/10.1056/nejmc1310150)), the gene represents a potential diagnostic marker for certain forms of female infertility. Therapeutic strategies would likely focus on gene activation or replacement, though these approaches remain challenging. Inhibition of [HFM1](/details-gene/164045) is unlikely to be a viable therapeutic strategy, as this would mimic the pathogenic state. Furthermore, its newly suggested, significant role in CNS vasculature and neurons raises a critical consideration: any systemic therapeutic targeting of [HFM1](/details-gene/164045) could carry a risk of unintended neurological or cerebrovascular side effects.

Genular Protein ID: 1507139982

Symbol: HFM1_HUMAN

Name: Probable ATP-dependent DNA helicase HFM1

UniProtKB Accession Codes:

A2PYH4 B1B0B6 Q8N9Q0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 6 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 2 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 6 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 5 Rhea 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 17286053

Title: HFM1, the human homologue of yeast Mer3, encodes a putative DNA helicase expressed specifically in germ-line cells.

PubMed ID: 17286053

DOI: 10.1080/10425170600805433

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 24597873

Title: Mutations in HFM1 in recessive primary ovarian insufficiency.

PubMed ID: 24597873

DOI: 10.1056/nejmc1310150

Sequence Information:

  • Length: 1435
  • Mass: 162610
  • Checksum: 9FEFDF74FB990741
  • Sequence:
    • MLKSNDCLFS LENLFFEKPD EVENHPDNEK SLDWFLPPAP LISEIPDTQE LEEELESHKL 
LGQEKRPKML TSNLKITNED TNYISLTQKF QFAFPSDKYE QDDLNLEGVG NNDLSHIAGK 
LTYASQKYKN HIGTEIAPEK SVPDDTKLVN FAEDKGESTS VFRKRLFKIS DNIHGSAYSN 
DNELDSHIGS VKIVQTEMNK GKSRNYSNSK QKFQYSANVF TANNAFSASE IGEGMFKAPS 
FSVAFQPHDI QEVTENGLGS LKAVTEIPAK FRSIFKEFPY FNYIQSKAFD DLLYTDRNFV 
ICAPTGSGKT VVFELAITRL LMEVPLPWLN IKIVYMAPIK ALCSQRFDDW KEKFGPIGLN 
CKELTGDTVM DDLFEIQHAH IIMTTPEKWD SMTRKWRDNS LVQLVRLFLI DEVHIVKDEN 
RGPTLEVVVS RMKTVQSVSQ TLKNTSTAIP MRFVAVSATI PNAEDIAEWL SDGERPAVCL 
KMDESHRPVK LQKVVLGFPC SSNQTEFKFD LTLNYKIASV IQMYSDQKPT LVFCATRKGV 
QQAASVLVKD AKFIMTVEQK QRLQKYAYSV RDSKLRDILK DGAAYHHAGM ELSDRKVVEG 
AFTVGDLPVL FTTSTLAMGV NLPAHLVVIK STMHYAGGLF EEYSETDILQ MIGRAGRPQF 
DTTATAVIMT RLSTRDKYIQ MLACRDTVES SLHRHLIEHL NAEIVLHTIT DVNIAVEWIR 
STLLYIRALK NPSHYGFASG LNKDGIEAKL QELCLKNLND LSSLDLIKMD EGVNFKPTEA 
GRLMAWYYIT FETVKKFYTI SGKETLSDLV TLIAGCKEFL DIQLRINEKK TLNTLNKDPN 
RITIRFPMEG RIKTREMKVN CLIQAQLGCI PIQDFALTQD TAKIFRHGSR ITRWLSDFVA 
AQEKKFAVLL NSLILAKCFR CKLWENSLHV SKQLEKIGIT LSNAIVNAGL TSFKKIEETD 
ARELELILNR HPPFGTQIKE TVMYLPKYEL KVEQITRYSD TTAEILVTVI LRNFEQLQTK 
RTASDSHYVT LIIGDADNQV VYLHKITDSV LLKAGSWAKK IAVKRALKSE DLSINLISSE 
FVGLDIQQKL TVFYLEPKRF GNQITMQRKS ETQISHSKHS DISTIAGPNK GTTASKKPGN 
RECNHLCKSK HTCGHDCCKI GVAQKSEIKE STISSYLSDL RNRNAVSSVP PVKRLKIQMN 
KSQSVDLKEF GFTPKPSLPS ISRSEYLNIS ELPIMEQWDQ PEIYGKVRQE PSEYQDKEVL 
NVNFELGNEV WDDFDDENLE VTSFSTDTEK TKISGFGNTL SSSTRGSKLP LQESKSKFQR 
EMSNSFVSSH EMSDISLSNS AMPKFSASSM TKLPQQAGNA VIVHFQERKP QNLSPEIEKQ 
CFTFSEKNPN SSNYKKVDFF IRNSECKKEV DFSMYHPDDE ADEMKSLLGI FDGIF