DHH (Desert Hedgehog) Gene
A key hedgehog signaling ligand involved in gonadal development and peripheral nerve sheath formation
Gene Information Card
| Symbol | DHH |
|---|---|
| Full Name | Desert Hedgehog Signaling Molecule |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.12 |
| NCBI Gene ID | 50846 ncbi.nlm.nih.gov/gene/50846 |
| Ensembl ID | ENSG00000154309 |
| UniProt ID | O43323 |
| OMIM ID | 605423 |
| HGNC ID | 2866 |
| Aliases | HHG-3, desert hedgehog homolog (Drosophila) |
Description
The DHH gene encodes desert hedgehog, a member of the hedgehog family of secreted signaling molecules. It plays a critical role in embryonic development, particularly in the formation of the gonads, peripheral nerves, and other tissues. DHH signals through the patched/smoothened receptor complex to regulate gene expression via GLI transcription factors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 46,XY gonadal dysgenesis (partial or complete) | Loss-of-function mutations impair DHH signaling in Sertoli cell precursors, disrupting testis development and leading to sex reversal or ambiguous genitalia. | OMIM, ClinVar |
| Minifascicular neuropathy | DHH mutations cause aberrant peripheral nerve development, leading to a distinct neuropathy with minifascicular formation on biopsy. | OMIM, PubMed |
| Gonadoblastoma (in context of dysgenesis) | Dysgenetic gonads with DHH mutations have increased risk of germ cell tumors, though direct mechanism is not fully defined. | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | Not available (GTEx) | High expression in Sertoli cells (protein level) |
| Peripheral nerve | Not available | Expressed in Schwann cells |
| Ovary | Not available | Low expression in granulosa cells |
| Placenta | Not available | Expression reported |
| Other tissues | Not available | Low or absent in most adult tissues |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NT2/D1 (embryonal carcinoma) | Not available | Expression reported in undifferentiated cells |
| Primary Sertoli cells | Not available | High expression |
| Schwann cells (primary) | Not available | Expression in myelinating cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.247C>T (p.Arg83Cys) | Missense | Rare | Loss of function; associated with 46,XY partial gonadal dysgenesis |
| c.302G>A (p.Trp101*) | Nonsense | Rare | Loss of function; causes complete gonadal dysgenesis |
| c.421C>T (p.Arg141Cys) | Missense | Rare | Loss of function; associated with minifascicular neuropathy |
| c.563G>A (p.Arg188His) | Missense | Rare | Loss of function; reported in gonadal dysgenesis |
Mutation functional classification
Loss of Function (LOF)
Most DHH mutations are loss-of-function, leading to reduced or absent signaling, causing developmental defects in gonads and nerves.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DHH.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with ligand processing or receptor binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (KEGG: hsa04340)
• Signaling by Hedgehog (Reactome: R-HSA-5358346)
Protein Summary
The DHH protein is a secreted ligand that undergoes autocatalytic cleavage to produce an N-terminal signaling domain. It binds to the Patched receptor, relieving inhibition of Smoothened, leading to activation of GLI transcription factors. DHH is essential for testicular development and peripheral nerve sheath integrity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DHH Knockout HEK293 Cell Line | EDJ-KQ890 | Human | 50846 | Details Get a Quote |
| DHH Knockout HeLa Cell Line | EDJ-KQ56196 | Human | 50846 | Details Get a Quote |
| DHH Knockout A-549 Cell Line | EDJ-KQ64686 | Human | 50846 | Details Get a Quote |
| DHH Knockout HCT 116 Cell Line | EDJ-KQ73134 | Human | 50846 | Details Get a Quote |
