DHH desert hedgehog signaling molecule [Homo sapiens (human)] - Gene

Summary

Official Symbol: DHHprovided by HGNC
Official Full Name: desert hedgehog signaling moleculeprovided by HGNC
Primary source: HGNC:HGNC:2865
See related: Ensembl:ENSG00000139549 MIM:605423; AllianceGenome:HGNC:2865
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GDMN; GDXYM; HHG-3; SRXY7
Summary: 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]
Expression: Biased expression in testis (RPKM 5.9) and appendix (RPKM 0.3) See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 12q13.12

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (49086656..49094801, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (49048829..49056982, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (49480439..49488584, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PKNOX1 acts as a transcription factor of DHH and promotes the progression of stomach adenocarcinoma by regulating the Hedgehog signalling pathway.
Title: PKNOX1 acts as a transcription factor of DHH and promotes the progression of stomach adenocarcinoma by regulating the Hedgehog signalling pathway.
Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.
Title: Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.
Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium.
Title: Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium.
DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation.
Title: DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation.
Our findings suggest heterozygous DHH gene variants are unlikely to cause DSD, reaffirming that DHH is an autosomal recessive cause of 46,XY gonadal dysgenesis.
Title: Functional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,XY differences of sex development.
Defects in the DHH gene have been reported as a very rare cause of Disorders of sex development, and this report increases the number of 46,XY gonadal dysgenesis cases.
Title: 46,XY complete gonadal dysgenesis in a familial case with a rare mutation in the desert hedgehog (DHH) gene.
Study describes two patients diagnosed with gonadal dysgenesis (GD), both harboring novel DHH compound heterozygous mutations p.[Tyr176*];[Asn337Lysfs*24] and p.[Tyr176*];[Glu212Lys]. While p.(Glu212Lys) retained 50% of its activity and led to a partially abolished DHH auto-processing, p.(Asn337Lysfs*24) resulted in a complete absence of auto-proteolysis.
Title: In vitro functional characterization of the novel DHH mutations p.(Asn337Lysfs*24) and p.(Glu212Lys) associated with gonadal dysgenesis.
Identify Dhh (desert hedgehog) as a downstream effector of Klf2, whose expression in endothelial cells is upregulated by shear stress and decreased by inflammatory cytokines.
Title: Restoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in Adults.
Whole-exome sequencing revealed a homozygous variant in DHH leading to the p.Trp173Cys substitution. The relevant Trp residue is conserved, and its alteration was predicted to be deleterious. Molecular dynamics simulations showed that the mutation increases the conformational flexibility of the protein
Title: A novel variant of DHH in a familial case of 46,XY disorder of sex development: Insights from molecular dynamics simulations.
Single nucleotide polymorphism in the DHH gene is associated with bipolar disorder.
Title: A genetic variant in 12q13, a possible risk factor for bipolar disorder, is associated with depressive state, accounting for stressful life events.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome MedGen: C5436061 OMIM: 607080 GeneReviews: Nonsyndromic Disorders of Testicular Development Overview	not available
46,XY sex reversal 7 MedGen: C1856273 OMIM: 233420 GeneReviews: Nonsyndromic Disorders of Testicular Development Overview	not available

EBI GWAS Catalog

Description
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

Dhh (e-PCR), detects polymorphism
- UniSTS:142848

Dhh (e-PCR), detects polymorphism
- UniSTS:464666

RH47641 (e-PCR)
- UniSTS:55265

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables cholesterol-protein transferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables patched binding	IBA Inferred from Biological aspect of Ancestor more info
enables patched binding	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Leydig cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell fate specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell signaling	IEA Inferred from Electronic Annotation more info
involved_in male sex determination	IEA Inferred from Electronic Annotation more info
involved_in myelination	IEA Inferred from Electronic Annotation more info
involved_in osteoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoprocessing	IEA Inferred from Electronic Annotation more info
involved_in regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of steroid biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to estrogen	IEA Inferred from Electronic Annotation more info
involved_in self proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in spermatid development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: desert hedgehog protein

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.