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 ... See more...

Aliases for HHIP Gene

Aliases for HHIP Gene

  • Hedgehog Interacting Protein 2 3 5
  • Hedgehog-Interacting Protein 2 3 4
  • HIP 2 3 4
  • FLJ20992 2
  • HHIP 5

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 Stature Quantitative Trait Locus 12 and Basal Cell Carcinoma. Among its related pathways are Signaling by GPCR and Signaling by Hedgehog. Gene Ontology (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 Summary 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 CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HHIP Gene

Genomics for HHIP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HHIP Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HHIP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HHIP

Top Transcription factor binding sites by QIAGEN in the HHIP gene promoter:
  • FAC1
  • GATA-6
  • GCNF
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • SRF
  • SRF (504 AA)
  • Zic1

Genomic Locations for HHIP Gene

Latest Assembly
chr4:144,646,154-144,745,271
(GRCh38/hg38)
Size:
99,118 bases
Orientation:
Plus strand

Previous Assembly
chr4:145,567,308-145,666,423
(GRCh37/hg19 by Entrez Gene)
Size:
99,116 bases
Orientation:
Plus strand

chr4:145,567,173-145,666,423
(GRCh37/hg19 by Ensembl)
Size:
99,251 bases
Orientation:
Plus strand

Genomic View for HHIP Gene

Genes around HHIP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HHIP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HHIP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HHIP Gene

Proteins for HHIP Gene

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

    Protein Symbol:
    Q96QV1-HHIP_HUMAN
    Recommended name:
    Hedgehog-interacting protein
    Protein Accession:
    Q96QV1
    Secondary Accessions:
    • Q6PK09
    • Q8NCI7
    • Q9BXK3
    • Q9H1J4
    • Q9H7E7

    Protein attributes for HHIP Gene

    Size:
    700 amino acids
    Molecular mass:
    78851 Da
    Quaternary structure:
    • Interacts with all three hedgehog family members, SHH, IHH and DHH.
    SequenceCaution:
    • Sequence=BAB14945.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: Potentially soluble form.

    Three dimensional structures from OCA and Proteopedia for HHIP Gene

    Alternative splice isoforms for HHIP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HHIP Gene

Post-translational modifications for HHIP Gene

  • Glycosylation at Asn99, Asn416, Asn447, and Asn459
  • Ubiquitination at Lys247, Lys270, and Lys659
  • Modification sites at PhosphoSitePlus

Other Protein References for HHIP Gene

No data available for DME Specific Peptides for HHIP Gene

Domains & Families for HHIP Gene

Gene Families for HHIP Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for HHIP Gene

GenScript: Design optimal peptide antigens:
  • Hedgehog-interacting protein (HHIP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96QV1

UniProtKB/Swiss-Prot:

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

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.

Phenotypes From GWAS Catalog for HHIP Gene

Gene Ontology (GO) - Molecular Function for HHIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0005515 protein binding IPI 19561609
GO:0008270 zinc ion binding IDA 19561609
GO:0046872 metal ion 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 Models for HHIP Gene

MGI Knock Outs for HHIP:

Animal Models for research

  • Taconic Biosciences Mouse Models for HHIP

miRNA for HHIP Gene

miRTarBase miRNAs that target HHIP

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HHIP

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , 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

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HHIP gene
Compartment Confidence
plasma membrane 5
extracellular 4
nucleus 4
cytoskeleton 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for HHIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane IEA --
GO:0005887 integral component of plasma membrane ISS 11435703
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

SIGNOR curated interactions for HHIP Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for HHIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA --
GO:0007405 neuroblast proliferation IEA --
GO:0009887 animal organ morphogenesis IEA --
GO:0009953 dorsal/ventral pattern formation IEA --
GO:0009968 negative regulation of signal transduction IDA 19561609
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

mRNA/cDNA for HHIP Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HHIP

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: -
SP3:
SP4: - - - -
SP5: -
SP6: -
SP7:

Relevant External Links for HHIP Gene

GeneLoc Exon Structure for
HHIP

Expression for HHIP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE 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, MaxQB, and MOPED for HHIP Gene



Protein tissue co-expression partners for HHIP Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HHIP

SOURCE GeneReport for Unigene cluster for HHIP Gene:

Hs.507991

mRNA Expression by UniProt/SwissProt for HHIP Gene:

Q96QV1-HHIP_HUMAN
Tissue specificity: Widely expressed in fetal and adult tissues. Highest expression in adult heart, liver and pancreas, and in fetal kidney.

Evidence on tissue expression from TISSUES for HHIP Gene

  • Nervous system(4.8)
  • Heart(4.4)
  • Muscle(4.3)
  • Kidney(3)
  • Lung(2.7)
  • Intestine(2.1)
  • Stomach(2.1)
  • Pancreas(2.1)
  • Liver(2)
genes like me logo Genes that share expression patterns with HHIP: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
Chimpanzee
(Pan troglodytes)
Mammalia HHIP 29 30
  • 99.52 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HHIP 29 30
  • 93.43 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HHIP 29 30
  • 91.76 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HHIP 30
  • 91 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia HHIP 30
  • 89 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Hhip 29 16 30
  • 88.62 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hhip 29
  • 88.43 (n)
Chicken
(Gallus gallus)
Aves HHIP 29 30
  • 80.98 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HHIP 30
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hhip 29
  • 77.69 (n)
Str.9010 29
African clawed frog
(Xenopus laevis)
Amphibia hhip-prov 29
Zebrafish
(Danio rerio)
Actinopterygii hhip 29 30
  • 66.76 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 25 (a)
OneToMany
Species where no ortholog for HHIP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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

ENSEMBL:
Gene Tree for HHIP (if available)
TreeFam:
Gene Tree for HHIP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HHIP: view image
Alliance of Genome Resources:
Additional Orthologs for HHIP

Paralogs for HHIP Gene

Paralogs for HHIP Gene

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

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

Variants for HHIP Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HHIP Gene

HHIP_HUMAN-Q96QV1
Genetic variations in HHIP define the stature quantitative trait locus 12 (STQTL12) [MIM:612224]. 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, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HHIP Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
870129 Association: Chronic obstructive pulmonary disease, biomass related; Chronic obstructive pulmonary disease 144,539,078(+) A/G
NC_000004.12:g.144539078A>G
870130 Association: Chronic obstructive pulmonary disease, biomass related; Chronic obstructive pulmonary disease 144,565,237(+) A/G
NC_000004.12:g.144565237A>G
870131 Association: Chronic obstructive pulmonary disease, biomass related; Chronic obstructive pulmonary disease 144,559,628(+) A/G
NC_000004.12:g.144559628A>G
rs114688020 Likely Benign: not provided 144,711,994(+) C/T
NM_022475.3(HHIP):c.1346C>T (p.Thr449Met)
MISSENSE
rs61730970 Benign: not provided 144,659,714(+) G/A
NM_022475.3(HHIP):c.707G>A (p.Gly236Glu)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HHIP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
esv2578862 CNV deletion 19546169
esv3340597 CNV insertion 20981092

Variation tolerance for HHIP Gene

Residual Variation Intolerance Score: 63.5% 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)

Additional Variant Information for HHIP Gene

Human Gene Mutation Database (HGMD)
HHIP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HHIP
Leiden Open Variation Database (LOVD)
HHIP

SNP Genotyping and Copy Number Assays for research

Disorders for HHIP Gene

MalaCards: The human disease database

(7) MalaCards diseases for HHIP Gene - From: COP and GCD

Disorder Aliases PubMed IDs
stature quantitative trait locus 12
  • stqtl12
basal cell carcinoma
  • basal cell cancer
chondrodysplasia, blomstrand type
  • bocd
holoprosencephaly
  • holoprosencephaly sequence
basal cell nevus syndrome
  • bcns
- elite association - COSMIC cancer census association via MalaCards
Search HHIP in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HHIP

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
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 (Cytogenetics and cell genetics 2001) 2 3 4 22
  2. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. (PMID: 19300482) Pillai SG … ICGN Investigators (PLoS genetics 2009) 3 22 40
  3. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. (PMID: 19300500) Wilk JB … O'Connor GT (PLoS genetics 2009) 3 22 40
  4. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP. (PMID: 19561611) Bishop B … Siebold C (Nature structural & molecular biology 2009) 3 4 22
  5. 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 RA (Nature structural & molecular biology 2009) 3 4 22

Products for HHIP Gene

Sources for HHIP Gene