This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating morphogenesis. This protein is predicted to be made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor process... See more...

Aliases for DHH Gene

Aliases for DHH Gene

  • Desert Hedgehog Signaling Molecule 2 3 5
  • HHG-3 2 3 4
  • Desert Hedgehog Protein 3 4
  • Desert Hedgehog (Drosophila) Homolog 2
  • Desert Hedgehog 2
  • MGC35145 2
  • GDXYM 3
  • SRXY7 3
  • DHH 5

External Ids for DHH Gene

Previous GeneCards Identifiers for DHH Gene

  • GC12P049326
  • GC12M049199
  • GC12M047769
  • GC12M049483
  • GC12M046514

Summaries for DHH Gene

Entrez Gene Summary for DHH Gene

  • This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating morphogenesis. This protein is predicted to be made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the organism. Defects in this protein have been associated with partial gonadal dysgenesis (PGD) accompanied by minifascicular polyneuropathy. This protein may be involved in both male gonadal differentiation and perineurial development. [provided by RefSeq, May 2010]

GeneCards Summary for DHH Gene

DHH (Desert Hedgehog Signaling Molecule) is a Protein Coding gene. Diseases associated with DHH include 46,Xy Gonadal Dysgenesis, Partial, With Minifascicular Neuropathy and 46,Xy Sex Reversal 7. Among its related pathways are Signaling by GPCR and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include calcium ion binding and patched binding. An important paralog of this gene is SHH.

UniProtKB/Swiss-Prot Summary for DHH Gene

  • Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development.

Gene Wiki entry for DHH Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DHH Gene

Genomics for DHH Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for DHH 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 DHH on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the DHH gene promoter:
  • c-Myc
  • C/EBPbeta
  • Egr-4
  • FOXD1
  • FOXL1
  • Max
  • Pax-4a
  • Pax-5
  • Roaz
  • Zic1

Genomic Locations for DHH Gene

Genomic Locations for DHH Gene
chr12:49,086,656-49,094,801
(GRCh38/hg38)
Size:
8,146 bases
Orientation:
Minus strand
chr12:49,483,204-49,488,602
(GRCh37/hg19)
Size:
5,399 bases
Orientation:
Minus strand

Genomic View for DHH Gene

Genes around DHH on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for DHH Gene

Proteins for DHH Gene

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

    Protein Symbol:
    O43323-DHH_HUMAN
    Recommended name:
    Desert hedgehog protein
    Protein Accession:
    O43323
    Secondary Accessions:
    • Q15794

    Protein attributes for DHH Gene

    Size:
    396 amino acids
    Molecular mass:
    43577 Da
    Quaternary structure:
    • Interacts with BOC and CDON. Interacts with HHIP.

    Three dimensional structures from OCA and Proteopedia for DHH Gene

neXtProt entry for DHH Gene

Post-translational modifications for DHH Gene

  • The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity. Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (N-product). This covalent modification appears to play an essential role in restricting the spatial distribution of the protein activity to the cell surface. The N-product is the active species in both local and long-range signaling, whereas the C-product has no signaling activity (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DHH Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for DHH Gene

Domains & Families for DHH Gene

Gene Families for DHH Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for DHH Gene

InterPro:
Blocks:
  • Hedgehog amino-terminal signaling domain
  • Sonic hedgehog protein signature
  • Hedgehog protein, hint region
  • Hedgehog/Intein hint domain, C-terminal
  • Hedgehog/DD-peptidase, zinc-binding motif
ProtoNet:

Suggested Antigen Peptide Sequences for DHH Gene

GenScript: Design optimal peptide antigens:
  • HHG-3 (DHH_HUMAN)
  • Mutant desert hedgehog (F6KSZ4_HUMAN)
  • Mutant desert hedgehog (F6KSZ5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43323

UniProtKB/Swiss-Prot:

DHH_HUMAN :
  • The desert hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
  • Belongs to the hedgehog family.
Domain:
  • The desert hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
Family:
  • Belongs to the hedgehog family.
genes like me logo Genes that share domains with DHH: view

Function for DHH Gene

Molecular function for DHH Gene

UniProtKB/Swiss-Prot Function:
Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development.
GENATLAS Biochemistry:
desert hedgehog,murine homolog,expressed in developing heart,putatively involved in regulating the cardiac development

LifeMap Function Summary for DHH Gene

During embryonic development, DHH as signaling molecule is secreted from the following cells

Phenotypes From GWAS Catalog for DHH Gene

Gene Ontology (GO) - Molecular Function for DHH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005113 patched binding IBA 21873635
GO:0005509 calcium ion binding IBA,IDA 19561611
GO:0005515 protein binding IPI 19561611
GO:0008233 peptidase activity IEA --
GO:0008270 zinc ion binding IDA 19561611
genes like me logo Genes that share ontologies with DHH: view
genes like me logo Genes that share phenotypes with DHH: view

Human Phenotype Ontology for DHH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for DHH Gene

MGI Knock Outs for DHH:
  • Dhh Dhh<tm1Amc>

Animal Model Products

CRISPR Products

miRNA for DHH Gene

miRTarBase miRNAs that target DHH

Inhibitory RNA Products

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

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

Localization for DHH Gene

Subcellular locations from UniProtKB/Swiss-Prot for DHH Gene

[Desert hedgehog protein N-product]: Cell membrane. Lipid-anchor. Extracellular side. Note=The N-terminal peptide remains associated with the cell surface. {ECO:0000250}.
[Desert hedgehog protein C-product]: Secreted, extracellular space. Note=The C-terminal peptide diffuses from the cell. {ECO:0000250}.

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 DHH gene
Compartment Confidence
plasma membrane 4
extracellular 4
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for DHH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA 21873635
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with DHH: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for DHH Gene

Pathways & Interactions for DHH Gene

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

Pathways by source for DHH Gene

1 KEGG pathway for DHH Gene
4 Qiagen pathways for DHH Gene
  • Activation of PKA through GPCR
  • Hedgehog Signaling in Mammals
  • Molecular Mechanisms of Cancer
  • PKA Signaling

Gene Ontology (GO) - Biological Process for DHH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001649 osteoblast differentiation IEA --
GO:0001708 cell fate specification IBA 21873635
GO:0006508 proteolysis IEA --
GO:0007224 smoothened signaling pathway IBA 21873635
GO:0007267 cell-cell signaling IEA --
genes like me logo Genes that share ontologies with DHH: view

No data available for SIGNOR curated interactions for DHH Gene

Drugs & Compounds for DHH Gene

(7) Drugs for DHH Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cyclopamine Pharma Hedgehog (Hh) signaling Inhibitor, Inhibitor of Hedgehog (Hh) signaling 0
GANT61 Pharma GLI antagonist 0
GDC-0449 (Vismodegib) Pharma Hedgehog antagonist,potent and selective 0
LY2940680 Pharma Hedgehog/SMO antagonist,inhibits Hh signaling 0
PF-5274857 Pharma Smo antagonist,potent and selective 0

(7) ApexBio Compounds for DHH Gene

Compound Action Cas Number
Cyclopamine Hedgehog (Hh) signaling Inhibitor 4449-51-8
GANT61 GLI antagonist 500579-04-4
GDC-0449 (Vismodegib) Hedgehog antagonist,potent and selective 879085-55-9
LY2940680 Hedgehog/SMO antagonist,inhibits Hh signaling 1258861-20-9
PF-5274857 Smo antagonist,potent and selective 1373615-35-0
Purmorphamine Hedgehog agonist 483367-10-8
SANT-1 Shh inhibitor,potent and cell-permeable 304909-07-7
genes like me logo Genes that share compounds with DHH: view

Transcripts for DHH Gene

mRNA/cDNA for DHH Gene

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

CRISPR Products

Inhibitory RNA Products

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

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

No ASD Table

Relevant External Links for DHH Gene

GeneLoc Exon Structure for
DHH

Expression for DHH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DHH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Nerve - Tibial (x20.9) and Testis (x16.1).

Protein differential expression in normal tissues from HIPED for DHH Gene

This gene is overexpressed in Serum (42.9) and Cerebrospinal fluid (22.3).

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



Protein tissue co-expression partners for DHH Gene

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

SOURCE GeneReport for Unigene cluster for DHH Gene:

Hs.524382

Evidence on tissue expression from TISSUES for DHH Gene

  • Nervous system(4.5)
  • Kidney(4.5)
  • Skin(2.7)
  • Pancreas(2.5)
  • Stomach(2.3)
  • Adrenal gland(2.3)
  • Blood(2.2)
  • Lung(2.2)
  • Muscle(2.1)
  • Heart(2.1)
  • Intestine(2)
  • Liver(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for DHH Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • skeleton
Regions:
Head and neck:
  • brain
  • head
  • pituitary gland
Thorax:
  • breast
  • clavicle
Pelvis:
  • fallopian tube
  • ovary
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vas deferens
  • vulva
Limb:
  • arm
  • digit
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • humerus
  • lower limb
  • radius
  • shin
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
General:
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with DHH: view

No data available for mRNA Expression by UniProt/SwissProt for DHH Gene

Orthologs for DHH Gene

This gene was present in the common ancestor of animals.

Orthologs for DHH Gene

Organism Taxonomy Gene Similarity Type Details
Platypus
(Ornithorhynchus anatinus)
Mammalia DHH 31
  • 96 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia DHH 30 31
  • 91.22 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Dhh 30 17 31
  • 88.83 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Dhh 30
  • 88.39 (n)
Dog
(Canis familiaris)
Mammalia DHH 30 31
  • 88.06 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia DHH 31
  • 68 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia dhh 30
  • 63.41 (n)
African clawed frog
(Xenopus laevis)
Amphibia dhh-A 30
Zebrafish
(Danio rerio)
Actinopterygii dhh 31
  • 46 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta hh 31 32
  • 42 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 43 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
Species where no ortholog for DHH 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)
  • Chicken (Gallus gallus)
  • Chimpanzee (Pan troglodytes)
  • 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)
  • 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)
  • Oppossum (Monodelphis domestica)
  • 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 DHH Gene

ENSEMBL:
Gene Tree for DHH (if available)
TreeFam:
Gene Tree for DHH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DHH: view image

Paralogs for DHH Gene

Paralogs for DHH Gene

(2) SIMAP similar genes for DHH Gene using alignment to 3 proteins:

  • DHH_HUMAN
  • F6KSZ4_HUMAN
  • F6KSZ5_HUMAN
genes like me logo Genes that share paralogs with DHH: view

Variants for DHH Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DHH Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
5012 Pathogenic: 46,XY gonadal dysgenesis, complete, dhh-related 49,089,963(-) GC/G FRAMESHIFT_VARIANT
735198 Likely Benign: not provided 49,091,396(-) G/A INTRON_VARIANT
772085 Benign: not provided 49,094,325(-) G/C MISSENSE_VARIANT
772189 Conflicting Interpretations: 46,XY sex reversal, type 7; 46,XY gonadal dysgenesis, complete, dhh-related 49,094,285(-) G/A SYNONYMOUS_VARIANT
775008 Benign: 46,XY sex reversal, type 7 49,094,321(-) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for DHH Gene

Variation tolerance for DHH Gene

Residual Variation Intolerance Score: 34.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.89; 18.59% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DHH Gene

Human Gene Mutation Database (HGMD)
DHH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DHH

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for DHH Gene

Disorders for DHH Gene

MalaCards: The human disease database

(21) MalaCards diseases for DHH Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
46,xy gonadal dysgenesis, partial, with minifascicular neuropathy
  • 46xy partial gonadal dysgenesis, with minifascicular neuropathy
46,xy sex reversal 7
  • srxy7
46,xy sex reversal
  • 46 xy gonadal dysgenesis
gonadal dysgenesis
  • gonadal dysgenesis syndrome
nonsyndromic disorders of testicular development
- elite association - COSMIC cancer census association via MalaCards
Search DHH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

DHH_HUMAN
  • Partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080]: Characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity. {ECO:0000269 PubMed:11017805}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
  • 46,XY sex reversal 7 (SRXY7) [MIM:233420]: A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. SRXY7 patients have no functional gonads. {ECO:0000269 PubMed:15356051}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
genes like me logo Genes that share disorders with DHH: view

No data available for Genatlas for DHH Gene

Publications for DHH Gene

  1. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. (PMID: 11017805) Umehara F … Osame M (American journal of human genetics 2000) 3 4 23
  2. All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner. (PMID: 20519495) Kavran JM … Leahy DJ (The Journal of biological chemistry 2010) 3 4
  3. 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
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. (PMID: 15356051) Canto P … Méndez JP (The Journal of clinical endocrinology and metabolism 2004) 3 4

Products for DHH Gene

Sources for DHH Gene