HHIP
protein-codinghedgehog interacting protein
Gene summary
This gene encodes a member of the hedgehog-interacting protein (HHIP) family. The hedgehog (HH) proteins are evolutionarily conserved protein, which are important morphogens for a wide range of developmental processes, including anteroposterior patterns of limbs and regulation of left-right asymmetry in embryonic development. Multiple cell-surface receptors are responsible for transducing and/or regulating HH signals. The HHIP encoded by this gene is a highly conserved, vertebrate-specific inhibitor of HH signaling. It interacts with all three HH family members, SHH, IHH and DHH. Two single nucleotide polymorphisms (SNPs) near this gene are significantly associated with risk of chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism in this gene is also strongly associated with human height.[provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~99.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HHIP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022475.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 80 | 1 | 1 | 82 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 81 | 2 | 1 | 84 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071920.1 | 13 | MANE Select | |
| Ensembl | ENSP00000296575.3 | 13 | MANE Select | |
| Ensembl | ENSP00000408587.2 | 4 | Standard | |
| Ensembl | ENSP00000408587.2 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hhip | Danio rerio | Structure: slow muscle cell Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Basal cell carcinoma - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Hedgehog signaling pathway - Homo sapiens (human)
- HH-Ncore
Biological Process
- smoothened signaling pathway
- neuroblast proliferation
- dorsal/ventral pattern formation
- negative regulation of signal transduction
- regulation of fibroblast growth factor receptor signaling pathway
Molecular Function
- catalytic activity
- protein binding
- zinc ion binding
- hedgehog family protein binding
Cellular Component
- extracellular region
- nucleus
- cytoplasm
- integral component of plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296575
- Coding exons
- 13
- Length
- 99251
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125747
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.36 | 302 | 376 | 0.802 | 0.0000188 | 4587 |
| Missense (PolyPhen) | 68 | 99.846 | 0.68105 | 1123 | ||
| Synonymous | -0.765 | 156 | 144 | 1.08 | 0.00000757 | 1337 |
| Loss of Function | 4.40 | 5 | 31.7 | 0.158 | 0.00000146 | 431 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family. {ECO:0000269|PubMed:11472839, ECO:0000269|PubMed:19561609}.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.361
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.820
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |