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Aliases for HHIP Gene

Aliases for HHIP Gene

  • Hedgehog Interacting Protein 2 3
  • HIP 3 4
  • Hedgehog-Interacting Protein 2

External Ids for HHIP Gene

Previous GeneCards Identifiers for HHIP Gene

  • GC04P146367
  • GC04P145939
  • GC04P146144
  • GC04P145924
  • GC04P145786
  • GC04P145567
  • GC04P141298

Summaries for HHIP Gene

Entrez Gene Summary for HHIP Gene

  • 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]

GeneCards Summary for HHIP Gene

HHIP (Hedgehog Interacting Protein) is a Protein Coding gene. Diseases associated with HHIP include basal cell carcinoma and holoprosencephaly. Among its related pathways are Signaling by GPCR and Pathways in cancer. GO annotations related to this gene include quinone binding and hedgehog family protein binding. An important paralog of this gene is HHIPL2.

UniProtKB/Swiss-Prot for HHIP Gene

  • Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.

Gene Wiki entry for HHIP Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HHIP Gene

Genomics for HHIP Gene

Regulatory Elements for HHIP Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for HHIP Gene

144,645,996 bp from pter
144,745,271 bp from pter
99,276 bases
Plus strand

Genomic View for HHIP Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
GeneLoc Logo Gene Density

RefSeq DNA sequence for HHIP Gene

Proteins for HHIP Gene

  • Protein details for HHIP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Hedgehog-interacting protein
    Protein Accession:
    Secondary Accessions:
    • Q6PK09
    • Q8NCI7
    • Q9BXK3
    • Q9H1J4
    • Q9H7E7

    Protein attributes for HHIP Gene

    700 amino acids
    Molecular mass:
    78851 Da
    Quaternary structure:
    • Interacts with all three hedgehog family members, SHH, IHH and DHH.
    • Sequence=BAB14945.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HHIP Gene

    Alternative splice isoforms for HHIP Gene


neXtProt entry for HHIP Gene

Proteomics data for HHIP Gene at MOPED

Post-translational modifications for HHIP Gene

  • Ubiquitination at Lys 247, Lys 270, and Lys 659
  • Glycosylation at Asn 99, Asn 416, Asn 447, and Asn 459
  • Modification sites at PhosphoSitePlus

Other Protein References for HHIP Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HHIP Gene

Domains & Families for HHIP Gene

Suggested Antigen Peptide Sequences for HHIP Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • A flexible loop interacts with the SHH zinc binding site and contributes to zinc binding
  • Belongs to the HHIP family.
  • A flexible loop interacts with the SHH zinc binding site and contributes to zinc binding
  • Contains 2 EGF-like domains.
  • Belongs to the HHIP family.
genes like me logo Genes that share domains with HHIP: view

No data available for Gene Families for HHIP Gene

Function for HHIP Gene

Molecular function for HHIP Gene

UniProtKB/Swiss-Prot Function:
Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.

Gene Ontology (GO) - Molecular Function for HHIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19561609
GO:0008270 zinc ion binding IDA 19561609
GO:0016901 oxidoreductase activity, acting on the CH-OH group of donors, quinone or similar compound as acceptor IEA --
GO:0048038 quinone binding IEA --
GO:0097108 hedgehog family protein binding IPI 19561611
genes like me logo Genes that share ontologies with HHIP: view
genes like me logo Genes that share phenotypes with HHIP: view

Animal Model Products

miRNA for HHIP Gene

miRTarBase miRNAs that target HHIP

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for HHIP Gene

Localization for HHIP Gene

Subcellular locations from UniProtKB/Swiss-Prot for HHIP Gene

Cell membrane; Peripheral membrane protein. Secreted. Note=The last 22 C-terminal amino acids may participate in cell membrane attachment.
Isoform 2: Cytoplasm.

Subcellular locations from

Jensen Localization Image for HHIP Gene COMPARTMENTS Subcellular localization image for HHIP gene
Compartment Confidence
plasma membrane 4
extracellular 3
nucleus 2

Gene Ontology (GO) - Cellular Components for HHIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005737 cytoplasm IEA --
GO:0005887 integral component of plasma membrane ISS 11435703
GO:0009986 cell surface IEA --
GO:0060170 ciliary membrane TAS --
genes like me logo Genes that share ontologies with HHIP: view

Pathways & Interactions for HHIP Gene

genes like me logo Genes that share pathways with HHIP: view

PCR Array Products

Interacting Proteins for HHIP Gene

SIGNOR curated interactions for HHIP Gene


Gene Ontology (GO) - Biological Process for HHIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0007165 signal transduction --
GO:0007224 smoothened signaling pathway IEA --
GO:0007405 neuroblast proliferation IEA --
GO:0009887 organ morphogenesis --
genes like me logo Genes that share ontologies with HHIP: view

Drugs & Compounds for HHIP Gene

(1) Additional Compounds for HHIP Gene - From: NovoSeek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HHIP: view

Transcripts for HHIP Gene

Unigene Clusters for HHIP Gene

Hedgehog interacting protein:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HHIP Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19 ^ 20
SP1: - - - - - - - -
SP2: -
SP4: - - - -
SP5: -
SP6: -

Relevant External Links for HHIP Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HHIP Gene

mRNA expression in normal human tissues for HHIP Gene

mRNA differential expression in normal tissues according to GTEx for HHIP Gene

This gene is overexpressed in Brain - Hippocampus (x5.6), Brain - Spinal cord (cervical c-1) (x4.4), Brain - Substantia nigra (x4.3), Brain - Amygdala (x4.1), and Brain - Putamen (basal ganglia) (x4.1).

Protein differential expression in normal tissues from HIPED for HHIP Gene

This gene is overexpressed in Breast (63.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MOPED, and MaxQB for HHIP Gene

SOURCE GeneReport for Unigene cluster for HHIP Gene Hs.507991

mRNA Expression by UniProt/SwissProt for HHIP Gene

Tissue specificity: Widely expressed in fetal and adult tissues. Highest expression in adult heart, liver and pancreas, and in fetal kidney.
genes like me logo Genes that share expression patterns with HHIP: view

Protein tissue co-expression partners for HHIP Gene

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for HHIP Gene

Orthologs for HHIP Gene

This gene was present in the common ancestor of chordates.

Orthologs for HHIP Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia HHIP 35
  • 91.76 (n)
  • 95.71 (a)
  • 96 (a)
(Canis familiaris)
Mammalia HHIP 35
  • 93.43 (n)
  • 96.57 (a)
  • 96 (a)
(Mus musculus)
Mammalia Hhip 35
  • 88.62 (n)
  • 94.29 (a)
Hhip 16
Hhip 36
  • 94 (a)
(Pan troglodytes)
Mammalia HHIP 35
  • 99.52 (n)
  • 99.71 (a)
  • 100 (a)
(Rattus norvegicus)
Mammalia Hhip 35
  • 88.43 (n)
  • 94.14 (a)
(Monodelphis domestica)
Mammalia HHIP 36
  • 91 (a)
(Ornithorhynchus anatinus)
Mammalia HHIP 36
  • 89 (a)
(Gallus gallus)
Aves HHIP 35
  • 80.98 (n)
  • 85.44 (a)
  • 87 (a)
(Anolis carolinensis)
Reptilia HHIP 36
  • 89 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hhip 35
  • 77.69 (n)
  • 82.4 (a)
Str.9010 35
African clawed frog
(Xenopus laevis)
Amphibia hhip-prov 35
(Danio rerio)
Actinopterygii hhip 35
  • 66.76 (n)
  • 68.17 (a)
hhip 36
  • 67 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 25 (a)
Species with no ortholog for HHIP:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HHIP Gene

Gene Tree for HHIP (if available)
Gene Tree for HHIP (if available)

Paralogs for HHIP Gene

Paralogs for HHIP Gene

(1) SIMAP similar genes for HHIP Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with HHIP: view

Variants for HHIP Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HHIP Gene

Genetic variations in HHIP define the stature quantitative trait locus 12 (STQTL12) [MIM:612226]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits

Sequence variations from dbSNP and Humsavar for HHIP Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type MAF
VAR_021518 -

Structural Variations from Database of Genomic Variants (DGV) for HHIP Gene

Variant ID Type Subtype PubMed ID
esv2578862 CNV Deletion 19546169

Variation tolerance for HHIP Gene

Residual Variation Intolerance Score: 63.51% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.02; 60.41% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HHIP Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

Disorders for HHIP Gene

MalaCards: The human disease database

(2) MalaCards diseases for HHIP Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
basal cell carcinoma
  • basal cell tumor
  • holoprosencephaly sequence
- elite association
Search HHIP in MalaCards View complete list of genes associated with diseases

Relevant External Links for HHIP

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with HHIP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HHIP Gene

Publications for HHIP Gene

  1. The human hedgehog-interacting protein gene: structure and chromosome mapping to 4q31.21-->q31.3. (PMID: 11435703) Bak M. … Tommerup N. (Cytogenet. Cell Genet. 2001) 2 23 67
  2. The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling. (PMID: 19561609) Bosanac I. … Lazarus R.A. (Nat. Struct. Mol. Biol. 2009) 23 67
  3. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. (PMID: 19300482) Pillai S.G. … Goldstein D.B. (PLoS Genet. 2009) 23 67
  4. Blocking the hedgehog pathway inhibits hepatoblastoma growth. (PMID: 19177589) EichenmA1ller M. … Kappler R. (Hepatology 2009) 23 67
  5. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. (PMID: 19300500) Wilk J.B. … O'Connor G.T. (PLoS Genet. 2009) 23 67

Products for HHIP Gene

Sources for HHIP Gene

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