HHIP Gene - Hedgehog Interacting Protein
Key regulator of Hedgehog signaling pathway
Gene Information Card
| Symbol | HHIP |
|---|---|
| Full Name | Hedgehog Interacting Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.21 |
| NCBI Gene ID | 64399 ncbi.nlm.nih.gov/gene/64399 |
| Ensembl ID | ENSG00000164161 |
| UniProt ID | Q96QV1 |
| OMIM ID | 606178 |
| HGNC ID | 14866 |
| Aliases | HIP, HIP1, MGC111111 |
Description
The HHIP gene encodes the hedgehog interacting protein, a key negative regulator of the Hedgehog signaling pathway. It binds to all three Hedgehog ligands (Sonic, Indian, and Desert) and limits their diffusion and activity. HHIP is involved in embryonic development, tissue patterning, and is implicated in various cancers and congenital disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lung cancer (non-small cell) | Reduced HHIP expression leads to aberrant Hedgehog pathway activation, promoting tumor growth | PMID: 23431142 |
| Congenital diaphragmatic hernia | Loss-of-function mutations disrupt Hedgehog signaling during diaphragm development | PMID: 25683121 |
| Holoprosencephaly | HHIP variants impair Sonic Hedgehog gradient formation, causing forebrain midline defects | PMID: 21763484 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Brain | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 7.8 | Moderate expression |
| HeLa (cervical carcinoma) | 5.1 | Low expression |
| HepG2 (hepatocellular carcinoma) | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.124C>T (p.Arg42Cys) | Missense | 0.02% | Reduced ligand binding affinity |
| c.856G>A (p.Gly286Arg) | Missense | 0.01% | Impaired protein stability |
Mutation functional classification
Loss of Function (LOF)
Most HHIP mutations are loss-of-function, reducing Hedgehog inhibition and leading to pathway overactivation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (Reactome: R-HSA-5358351)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
The HHIP protein is a 700-amino acid transmembrane glycoprotein that functions as a negative regulator of Hedgehog signaling. It binds directly to Hedgehog ligands (SHH, IHH, DHH) with high affinity, sequestering them and preventing their interaction with the Patched receptor. This limits the range and intensity of Hedgehog signals during development and tissue homeostasis. HHIP is expressed in various tissues, with highest levels in lung and brain. Dysregulation of HHIP is associated with lung cancer, congenital diaphragmatic hernia, and holoprosencephaly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HHIP Knockout HEK293 Cell Line | EDJ-KQ1807 | Human | 64399 | Details Get a Quote |
| HHIPL1 Knockout HEK293 Cell Line | EDJ-KQ10093 | Human | 84439 | Details Get a Quote |
| HHIPL2 Knockout HEK293 Cell Line | EDJ-KQ13748 | Human | 79802 | Details Get a Quote |
| HHIP Knockout HeLa Cell Line | EDJ-KQ20333 | Human | 64399 | Details Get a Quote |
| HHIPL2 Knockout A-549 Cell Line | EDJ-KQ43517 | Human | 79802 | Details Get a Quote |
| HHIPL2 Knockout HeLa Cell Line | EDJ-KQ57233 | Human | 79802 | Details Get a Quote |
| HHIPL1 Knockout HeLa Cell Line | EDJ-KQ57594 | Human | 84439 | Details Get a Quote |
| HHIP Knockout A-549 Cell Line | EDJ-KQ65565 | Human | 64399 | Details Get a Quote |
| HHIPL1 Knockout A-549 Cell Line | EDJ-KQ66091 | Human | 84439 | Details Get a Quote |
| HHIP Knockout HCT 116 Cell Line | EDJ-KQ73994 | Human | 64399 | Details Get a Quote |
| HHIPL2 Knockout HCT 116 Cell Line | EDJ-KQ74162 | Human | 79802 | Details Get a Quote |
| HHIPL1 Knockout HCT 116 Cell Line | EDJ-KQ74514 | Human | 84439 | Details Get a Quote |
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