DHH

Protein identityUniProt · HPA

UniProt accession

O43323

Gene

DHH

Ensembl

ENSG00000139549

Chromosome

12

Canonical length

396 aa

Protein class

Disease related genes, Human disease related genes, Predicted secreted proteins

Secretome location

Secreted in male reproductive system

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

396 residues, UniProt reviewed canonical sequence.

>O43323|DHH
     1  MALLTNLLPL CCLALLALPA QSCGPGRGPV GRRRYARKQL VPLLYKQFVP GVPERTLGAS
    61  GPAEGRVARG SERFRDLVPN YNPDIIFKDE ENSGADRLMT ERCKERVNAL AIAVMNMWPG
   121  VRLRVTEGWD EDGHHAQDSL HYEGRALDIT TSDRDRNKYG LLARLAVEAG FDWVYYESRN
   181  HVHVSVKADN SLAVRAGGCF PGNATVRLWS GERKGLRELH RGDWVLAADA SGRVVPTPVL
   241  LFLDRDLQRR ASFVAVETEW PPRKLLLTPW HLVFAARGPA PAPGDFAPVF ARRLRAGDSV
   301  LAPGGDALRP ARVARVAREE AVGVFAPLTA HGTLLVNDVL ASCYAVLESH QWAHRAFAPL
   361  RLLHALGALL PGGAVQPTGM HWYSRLLYRL AEELLG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DHH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

9.8 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DHH.

Disease | AllUniProt

Conditions DHH is implicated in, by any mechanism.

• 46,XY gonadal dysgenesis with minifascicular neuropathy (GDMN) MIM:607080
• 46,XY sex reversal 7 (SRXY7) MIM:233420

Disease | GeneticClinVar

19 pathogenic / likely-pathogenic of 147 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• 46,XY sex reversal 7
• 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome
• Differences in sex development
• DHH-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.68

gnomAD pLI

0.22

gnomAD missense Z

1.64

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell fate specification
• cell-cell signaling
• Leydig cell differentiation
• male sex determination
• myelination
• osteoblast differentiation
• positive regulation of smoothened signaling pathway
• protein autoprocessing
• regulation of gene expression
• regulation of steroid biosynthetic process
• response to estradiol
• response to estrogen
• self proteolysis
• smoothened signaling pathway
• spermatid development

Molecular functions

• calcium ion binding
• cholesterol-protein transferase activity
• patched binding
• peptidase activity
• zinc ion binding

Cellular components

• endoplasmic reticulum membrane
• extracellular space
• Golgi membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Hedgehog, N-terminal signalling domain
• Hedgehog protein
• Hedgehog protein, Hint domain
• Hint domain C-terminal
• Hint domain N-terminal
• Peptidase M74/Hedgehog-like, zinc-binding domain superfamily
• Hint domain superfamily
• Hedgehog Signaling
• Hint module
• Hedgehog amino-terminal signalling domain

KeywordsUniProt

• Autocatalytic cleavage
• Calcium
• Cell membrane
• Developmental protein
• Endoplasmic reticulum
• Golgi apparatus
• Hydrolase
• Lipoprotein
• Membrane
• Metal-binding
• Palmitate
• Protease
• Secreted
• Signal
• Transferase
• Zinc

InteractionsUniProt · HPA

Protein binding partners of DHH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BOC
• CDON
• HHIP