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FLASH GENE

Symbol

IHH

contributors: mct - updated : 10-01-2024

HGNC name	Indian hedgehog homolog (Drosophila)
HGNC id	5956

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ACFD acrocapitofemoral dysplasia BDA1 brachydactyly type A1, locus 1
Location	2q35      Physical location : 219.919.142 - 219.925.238
Synonym name	Indian hedgehog homolog
Synonym symbol(s)	HHG2, HHG-2, BDA1

DNA

TYPE	functioning gene
STRUCTURE	6.49 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002181 3 - 2074 NP_002172 - 411 - 1998 9593755

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Reproductive male system prostate       Urinary kidney         Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Connective cartilage     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive enterocyte not specific chondrocyte Homo sapiens Skeleton osteoblast

cell lineage
cell lines	metastatic and localized prostate cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

isoforms

Precursor

cleaved by autoproteolysis followed by attachment of cholesterol to the C terminus of the active N product

HOMOLOGY

interspecies

homolog to Drosophila segment polarity gene,indian hedgehog

intraspecies

homolog to indian hedgehog

Homologene

FAMILY

hedgehog family

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
text	anchored by its C terminus to the plasma membrane, cytoplasmic C terminus, also a secreted form

basic FUNCTION	required for the vertebrate skeletal development
	regulating chondrocyte proliferation
	activating the target genes involved in endochondral ossification
	inducing the expression of parathyroid hormone-like hormone PTHLH
	regulating enterocytes differentiation
	playing a dual role in promoting growth and metastasis of prostate cancer
	directly accelerates chondrocyte proliferation, and regulates chondrocyte hypertrophy via parathyroid-hormone related protein (PTHLH) through a negative feedback mechanism
	in limb development, acts later as SHH and is thought not to affect patterning, but to regulate endochondral bone formation by controlling chondrogenic differentiation and proliferation
	play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints
	IHH promotes cartilage endplate degeneration
	IHH has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium
	IHH, which regulates skeletal development including synovial joint formation, also plays pivotal roles in temporomandibular joint (TMJ) development and postnatal maintenance
	involved in regulation of chondrocyte differentiation via a negative feedback loop formed together with parathyroid hormone-related protein (PTHrP), in promotion of chondrocyte proliferation, and in specification of bone-forming osteoblasts
	critical role of epithelium-derived IHH as a stromal tumor suppressor in the intestine
	SHH and IHH have been shown to control the induction of early cartilaginous differentiation
	IHH and SHH have synergistic effects on the induction of chondrogenic differentiation and chondrogenesis under a microgravity environment, and help to repair damaged cartilage and reverse subchondral defects during the early stages

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

IHH pathway plays an essential role in facilitating chondrocyte hypertrophy and bone formation during skeletal development

a component

INTERACTION

DNA

RNA

small molecule

protein	FGFR3
	binding to the patched receptor activation the target genes involved in endochondrial ossification
	inducing the expression of parathyroid hormone-like hormone PTHLH
	GLI gene in mediating the carcinogenic effect of hedgehog pathway activation
	SMO (essential for the HH signaling)
	canonical Wnt/CTNNB pathway probably mediates regulation of IHH expression in prehypertrophic chondrocytes by WNT9A
	interacting with FGF8 (maybe playing different roles and acting synergistically to promote chondrogenesis during digit primordia elongation)
	ATF4 activates BGLAP in osteoblasts and indian hedgehog (IHH) in chondrocytes
	IHH signalling can induce proteasomal degradation of NKX3-2
	RUNX2 plays a major role in chondrocyte maturation, and regulates chondrocyte proliferation by directly regulating IHH expression
	IHH in SP7-expressing cells plays an indispensable role in osteoblast differentiation, mineralization, and embryonic osteogenesis

cell & other

REGULATION

inhibited by

negatively regulated by WNT signaling in colonic epithelial cell differentiation

ASSOCIATED DISORDERS

corresponding disease(s)

BDA1 , ACFD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in colon cancer with APC mutations constitutional     --over   in women with endometriosis tumoral     --low   by hypermethylation in colon cancer cell lines 9) constitutional   amplification     duplication involving the IHH locus mimics acrocallosal syndrome, with with extensive polysyndactyly of the hands and feet, craniofacial abnormalities including macrocephaly, agenesis of the corpus callosum, dysplastic and low-set ears, severe hypertelorism and profound psychomotor delay

Susceptibility

the development of retinopathy of prematurity (ROP)

Variant & Polymorphism SNP	association between SNPs and the development of ROP

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   blocking IHH has potential clinical usage for attenuating cartilage endplate (CEP) degeneration

ANIMAL & CELL MODELS

	SHH/IHH composed mutants have developmental defects at the somite stages with a small heart tube,an open gut and cyclopia
	mouse model recapitulating the E95K mutation, with a change in the potency and range of signalling; the mice have digit abnormalities consistent with the human disorder
	Ihh ablation in Sp7-expressing cells of mice resulted in a dwarfism phenotype with severe skeletal dysplasia and lethality at birth, but with normal joint segmentation