DND1: A Key Regulator of Germ Cell Development and Tumor Suppression
Comprehensive genomic and functional analysis of DND1, a microRNA-mediated deadenylation factor implicated in germ cell tumors and developmental disorders.
Gene Information Card
| Symbol | DND1 |
|---|---|
| Full Name | DND microRNA-mediated repression inhibitor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.3 |
| NCBI Gene ID | 373863 ncbi.nlm.nih.gov/gene/373863 |
| Ensembl ID | ENSG00000164330 |
| UniProt ID | Q8IYX4 |
| OMIM ID | 609385 |
| HGNC ID | 24799 |
| Aliases | RBMS4, MGC33894, DND1 (dead end homolog 1) |
Description
DND1 (DND microRNA-mediated repression inhibitor 1) encodes an RNA-binding protein that functions as a suppressor of microRNA-mediated gene silencing. It is essential for primordial germ cell (PGC) survival and migration during embryonic development. DND1 binds to the 3' UTR of target mRNAs and blocks the access of microRNAs, thereby protecting germ cell-specific transcripts from repression. Loss-of-function mutations in DND1 are associated with increased susceptibility to testicular germ cell tumors (TGCT) and impaired gametogenesis. The gene is also implicated in certain somatic cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Testicular germ cell tumor (TGCT) | Loss-of-function variants impair DND1's ability to protect germ cell mRNAs from microRNA repression, leading to aberrant germ cell proliferation and tumorigenesis. | ClinVar, OMIM #609385, NCBI Gene |
| Spermatogenic failure / infertility | DND1 deficiency disrupts primordial germ cell maintenance and differentiation, resulting in reduced or absent sperm production. | OMIM #609385, NCBI Gene |
| Ovarian germ cell tumor | Similar mechanism as TGCT; DND1 loss may contribute to dysregulation of germ cell development in the ovary. | COSMIC, NCBI Gene |
| Melanoma | DND1 overexpression or mutation may alter microRNA regulation of oncogenes or tumor suppressors in melanocytes. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Ovary | 3.2 | Low |
| Skin | 1.8 | Low |
| Brain | 0.5 | Not detected |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NTERA-2 (embryonal carcinoma) | 18.7 | High expression; germ cell tumor model |
| Seminoma cell lines (e.g., TCam-2) | 15.2 | High expression; relevant to TGCT |
| HeLa | 0.8 | Low expression |
| HEK293 | 0.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3G>A (p.Met1?) | Missense / start loss | Rare | Loss of translation initiation; likely loss-of-function |
| c.271C>T (p.Arg91*) | Nonsense | Rare | Premature stop; loss-of-function |
| c.364_365del (p.Leu122Valfs*2) | Frameshift | Rare | Frameshift leading to truncated protein; loss-of-function |
| c.470A>G (p.Asn157Ser) | Missense | Rare | Reduced RNA-binding affinity; partial loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Most reported DND1 mutations (nonsense, frameshift, start loss) lead to loss of protein function, impairing microRNA repression and increasing germ cell tumor risk.
Gain of Function (GOF)
No gain-of-function mutations have been characterized for DND1.
Dominant Negative (DN)
Some missense variants (e.g., p.Asn157Ser) may act in a dominant-negative manner by competing with wild-type DND1 for RNA binding, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• miRNA-mediated gene silencing (via DND1 blocking RISC access)
• Germ cell development (PGC migration and survival)
• p53 pathway (indirect regulation via miRNA targets)
Protein Summary
DND1 is a 339-amino acid RNA-binding protein containing two RRM (RNA recognition motif) domains. It localizes to both the nucleus and cytoplasm. DND1 specifically binds to the 3' UTR of target mRNAs and prevents microRNA-mediated deadenylation and translational repression. This function is critical for maintaining expression of germ cell-specific genes during development. The protein is highly expressed in testis and ovary, and its loss predisposes to germ cell tumors. Structural studies indicate that the RRM domains are essential for RNA binding and that mutations in these regions disrupt function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DND1 Knockout HEK293 Cell Line | EDJ-KQ13193 | Human | 373863 | Details Get a Quote |
| DND1 Knockout HeLa Cell Line | EDJ-KQ59890 | Human | 373863 | Details Get a Quote |
| DND1 Knockout A-549 Cell Line | EDJ-KQ68353 | Human | 373863 | Details Get a Quote |
| DND1 Knockout HCT 116 Cell Line | EDJ-KQ76728 | Human | 373863 | Details Get a Quote |
