DHH (desert hedgehog signaling molecule)

Gene

• Entrez ID: 50846
• Gene name: Desert hedgehog signaling molecule
• Gene symbol: DHH
• Synonyms (NCBI Gene): GDMN, GDXYM, HHG-3, SRXY7
• Chromosome: 12
• Chromosome location: 12q13.12
• 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-t

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017109	hsa-miR-335-5p	Microarray	18185580
MIRT934879	hsa-miR-1324	CLIP-seq
MIRT934880	hsa-miR-155	CLIP-seq
MIRT934881	hsa-miR-2053	CLIP-seq
MIRT934882	hsa-miR-3064-5p	CLIP-seq
MIRT934883	hsa-miR-3163	CLIP-seq
MIRT934884	hsa-miR-340	CLIP-seq
MIRT934885	hsa-miR-365	CLIP-seq
MIRT934886	hsa-miR-4687-3p	CLIP-seq
MIRT934887	hsa-miR-569	CLIP-seq
MIRT934888	hsa-miR-592	CLIP-seq
MIRT934889	hsa-miR-597	CLIP-seq
MIRT1547958	hsa-miR-145	CLIP-seq
MIRT1547959	hsa-miR-4287	CLIP-seq
MIRT1547960	hsa-miR-4304	CLIP-seq
MIRT1547961	hsa-miR-4685-3p	CLIP-seq
MIRT1547958	hsa-miR-145	CLIP-seq
MIRT1547959	hsa-miR-4287	CLIP-seq
MIRT1547960	hsa-miR-4304	CLIP-seq
MIRT1547961	hsa-miR-4685-3p	CLIP-seq
MIRT934879	hsa-miR-1324	CLIP-seq
MIRT934880	hsa-miR-155	CLIP-seq
MIRT934881	hsa-miR-2053	CLIP-seq
MIRT934885	hsa-miR-365	CLIP-seq
MIRT934886	hsa-miR-4687-3p	CLIP-seq
MIRT934887	hsa-miR-569	CLIP-seq
MIRT934888	hsa-miR-592	CLIP-seq
MIRT934889	hsa-miR-597	CLIP-seq
MIRT934879	hsa-miR-1324	CLIP-seq
MIRT934880	hsa-miR-155	CLIP-seq
MIRT934881	hsa-miR-2053	CLIP-seq
MIRT934885	hsa-miR-365	CLIP-seq
MIRT934886	hsa-miR-4687-3p	CLIP-seq
MIRT934887	hsa-miR-569	CLIP-seq
MIRT934888	hsa-miR-592	CLIP-seq
MIRT934889	hsa-miR-597	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0001649	Process	Osteoblast differentiation	IEA
GO:0001708	Process	Cell fate specification	IBA
GO:0005113	Function	Patched binding	IBA
GO:0005113	Function	Patched binding	IDA	11472839, 33063110
GO:0005113	Function	Patched binding	IEA
GO:0005509	Function	Calcium ion binding	IBA
GO:0005509	Function	Calcium ion binding	IDA	19561611
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	19561611, 20519495
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005886	Component	Plasma membrane	IDA	24342078
GO:0005886	Component	Plasma membrane	IEA
GO:0006508	Process	Proteolysis	IEA
GO:0007224	Process	Smoothened signaling pathway	IBA
GO:0007224	Process	Smoothened signaling pathway	IEA
GO:0007267	Process	Cell-cell signaling	IEA
GO:0007286	Process	Spermatid development	IEA
GO:0007286	Process	Spermatid development	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008233	Function	Peptidase activity	ISS
GO:0008270	Function	Zinc ion binding	IDA	19561611
GO:0010468	Process	Regulation of gene expression	IBA
GO:0016020	Component	Membrane	IEA
GO:0016540	Process	Protein autoprocessing	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030238	Process	Male sex determination	IEA
GO:0032355	Process	Response to estradiol	IEA
GO:0033327	Process	Leydig cell differentiation	IEA
GO:0042552	Process	Myelination	IEA
GO:0043627	Process	Response to estrogen	IEA
GO:0045880	Process	Positive regulation of smoothened signaling pathway	IDA	24342078, 33063110
GO:0045880	Process	Positive regulation of smoothened signaling pathway	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050810	Process	Regulation of steroid biosynthetic process	IEA
GO:0097264	Process	Self proteolysis	ISS
GO:0140853	Function	Cholesterol-protein transferase activity	ISS

Other IDs

• MIM: 605423
• HGNC: 2865
• e!Ensembl: ENSG00000139549

Protein

• UniProt ID: O43323
• Protein name: Desert hedgehog protein (DHH) (EC 3.1.-.-) (HHG-3) [Cleaved into: Desert hedgehog protein N-product (DHH-N)]
• Protein function: [Desert hedgehog protein]: The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into tw
• PDB: 2WFQ, 2WFR, 2WG3, 3N1G, 3N1Q
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01085	HH_signal	23 → 185	Hedgehog amino-terminal signalling domain	Domain
  PF01079	Hint	188 → 396	Hint module	Family

• Sequence:

  MALLTNLLPLCCLALLALPAQSCGPGRGPVGRRRYARKQLVPLLYKQFVPGVPERTLGAS
  GPAEGRVARGSERFRDLVPNYNPDIIFKDEENSGADRLMTERCKERVNALAIAVMNMWPG
  VRLRVTEGWDEDGHHAQDSLHYEGRALDITTSDRDRNKYGLLARLAVEAGFDWVYYESRN
  HVHVSVKADNSLAVRAGGCFPGNATVRLWSGERKGLRELHRGDWVLAADASGRVVPTPVL
  LFLDRDLQRRASFVAVETEWPPRKLLLTPWHLVFAARGPAPAPGDFAPVFARRLRAGDSV
  LAPGGDALRPARVARVAREEAVGVFAPLTAHGTLLVNDVLASCYAVLESHQWAHRAFAPL
  RLLHALGALLPGGAVQPTGMHWYSRLLYRLAEELLG

• Sequence length: 396

Pathways

KEGG:

Hedgehog signaling pathway

Reactome:

Hedgehog ligand biogenesis
Release of Hh-Np from the secreting cell
Ligand-receptor interactions
Activation of SMO
HHAT G278V abrogates palmitoylation of Hh-Np

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome	Pathogenic	rs104894346, rs1565573892, rs1939296210, rs1939295073	RCV000005313 RCV000678493 RCV001260584 RCV001260585	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
46,XY sex reversal 7	Pathogenic; Likely pathogenic	rs2120821285, rs111033589, rs1592184934, rs867798393, rs1565573786, rs1565572949, rs1480612338	RCV002249862 RCV000005314 RCV000005315 RCV000256189 RCV000714234 RCV000714235 RCV000714236 RCV000714237	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
DHH-related disorder	Likely pathogenic	rs1178487029	RCV003893731	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
46,XY COMPLETE GONADAL DYSGENESIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
46,XY DSD/46,XY CGD	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR I DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Disorder of sexual differentiation	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GONADAL DYSGENESIS, 46,XY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SWYER SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
46,XY complete gonadal dysgenesis	46, XY complete gonadal dysgenesis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
46,XY Gonadal Dysgenesis, Complete or Partial, DHH-Related	46, XY Gonadal Dysgenesis	UNIPROT_DG	15356051		★☆☆☆☆ Found in Text Mining only
46,XY Gonadal Dysgenesis, Complete or Partial, DHH-Related	46, XY Gonadal Dysgenesis	GENOMICS_ENGLAND_DG	21816240		★☆☆☆☆ Found in Text Mining only
46,XY Gonadal Dysgenesis, Complete or Partial, DHH-Related	46, XY Gonadal Dysgenesis	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
46,XY Gonadal Dysgenesis, Complete or Partial, DHH-Related	46, XY Gonadal Dysgenesis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
46,Xy Gonadal Dysgenesis, Partial, With Minifascicular Neuropathy	46, XY Gonadal Dysgenesis, With Minifascicular Neuropathy	ORPHANET_DG	11017805		★☆☆☆☆ Found in Text Mining only
46,Xy Gonadal Dysgenesis, Partial, With Minifascicular Neuropathy	46, XY Gonadal Dysgenesis, With Minifascicular Neuropathy	GENOMICS_ENGLAND_DG	21816240		★☆☆☆☆ Found in Text Mining only
46,Xy Gonadal Dysgenesis, Partial, With Minifascicular Neuropathy	46, XY Gonadal Dysgenesis, With Minifascicular Neuropathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
46,Xy Gonadal Dysgenesis, Partial, With Minifascicular Neuropathy	46, XY Gonadal Dysgenesis, With Minifascicular Neuropathy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome	46, XY gonadal dysgenesis-motor and sensory neuropathy syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Bipolar Disorder	Bipolar disorder	Pubtator	23070075, 25517604	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar Disorder	BEFREE	25517604		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cryptorchidism	Cryptorchidism	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	25517604		★☆☆☆☆ Found in Text Mining only
Depressive Disorder	Major depressive disorder	Pubtator	25517604	Associate	★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis	Gonadal Dysgenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadal dysgenesis with female appearance, male	Gonadal dysgenesis with female appearance, male	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis, 46,XY	Gonadal Dysgenesis	BEFREE	29471294		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gonadal Dysgenesis, 46,XY	Gonadal Dysgenesis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gonadoblastoma	Gonadoblastoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias, perineal	Hypospadias	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	25517604		★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	17952613		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	25517604		★☆☆☆☆ Found in Text Mining only
Micropenis	Micropenis	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29329585		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	11017805		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	17083567	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	29471294		★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	29471294		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	25517604		★☆☆☆☆ Found in Text Mining only
Sensorimotor neuropathy	Sensorimotor neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Streak ovary	Streak ovary	HPO_DG			★☆☆☆☆ Found in Text Mining only
Swyer Syndrome	Swyer Syndrome	BEFREE	21816240, 31240586		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Testicular dysgenesis	Testicular dysgenesis	CLINVAR_DG	30298535		★☆☆☆☆ Found in Text Mining only
Testicular dysgenesis	Testicular dysgenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Testicular hypogonadism	Testicular Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only