HHIP hedgehog interacting protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: HHIPprovided by HGNC
Official Full Name: hedgehog interacting proteinprovided by HGNC
Primary source: HGNC:HGNC:14866
See related: Ensembl:ENSG00000164161 MIM:606178; AllianceGenome:HGNC:14866
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: HIP
Summary: This gene encodes a member of the hedgehog-interacting protein (HHIP) family. The hedgehog (HH) proteins are evolutionarily conserved protein, which are important morphogens for a wide range of developmental processes, including anteroposterior patterns of limbs and regulation of left-right asymmetry in embryonic development. Multiple cell-surface receptors are responsible for transducing and/or regulating HH signals. The HHIP encoded by this gene is a highly conserved, vertebrate-specific inhibitor of HH signaling. It interacts with all three HH family members, SHH, IHH and DHH. Two single nucleotide polymorphisms (SNPs) near this gene are significantly associated with risk of chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism in this gene is also strongly associated with human height.[provided by RefSeq, Feb 2011]
Expression: Biased expression in lung (RPKM 8.1), brain (RPKM 4.1) and 12 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q31.21

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (144646156..144745271)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (147963548..148062608)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (145567308..145666423)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Impact of HHIP gene polymorphisms on phenotypes, serum IL-17 and IL-18 in COPD patients of the Chinese Han population.
Title: Impact of HHIP gene polymorphisms on phenotypes, serum IL-17 and IL-18 in COPD patients of the Chinese Han population.
Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells.
Title: Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells.
Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog interacting protein.
Title: Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog interacting protein.
Natural Antisense Long Noncoding RNA HHIP-AS1 Suppresses Non-Small-Cell Lung Cancer Progression by Increasing HHIP Stability via Interaction with CELF2.
Title: Natural Antisense Long Noncoding RNA HHIP-AS1 Suppresses Non-Small-Cell Lung Cancer Progression by Increasing HHIP Stability via Interaction with CELF2.
Association of human Hedgehog interacting protein gene polymorphisms with the risk of chronic obstructive pulmonary disease: a meta-analysis.
Title: Association of human Hedgehog interacting protein gene polymorphisms with the risk of chronic obstructive pulmonary disease: a meta-analysis.
Differential promoter usages of PTCH1 and down regulation of HHIP are associated with HNSCC progression.
Title: Differential promoter usages of PTCH1 and down regulation of HHIP are associated with HNSCC progression.
Long noncoding RNA HHIPAS1 inhibits lung cancer epithelialmesenchymal transition and stemness by regulating PCDHGA9.
Title: Long non‑coding RNA HHIP‑AS1 inhibits lung cancer epithelial‑mesenchymal transition and stemness by regulating PCDHGA9.
Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling.
Title: Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling.
Hedgehog interacting protein (HHIP) represses airway remodeling and metabolic reprogramming in COPD-derived airway smooth muscle cells.
Title: Hedgehog interacting protein (HHIP) represses airway remodeling and metabolic reprogramming in COPD-derived airway smooth muscle cells.
Downregulation of hedgehog-interacting protein (HHIP) contributes to hexavalent chromium-induced malignant transformation of human bronchial epithelial cells.
Title: Downregulation of hedgehog-interacting protein (HHIP) contributes to hexavalent chromium-induced malignant transformation of human bronchial epithelial cells.

Submit: New GeneRIF Correction See all GeneRIFs (63)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of pulmonary function measures in the Framingham Heart Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
A novel common variant in DCST2 is associated with length in early life and height in adulthood. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 20 loci that influence adult height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-Wide Association Identifies Regulatory Loci Associated with Distinct Local Histogram Emphysema Patterns. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies five loci associated with lung function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of height and body mass index in Australian twin families. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of ten loci associated with height highlights new biological pathways in human growth. EBI GWAS Catalog EBI GWAS CatalogPubMed
IREB2 and GALC are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size. EBI GWAS Catalog EBI GWAS CatalogPubMed
Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in FAM13A are associated with chronic obstructive pulmonary disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with HHIP; predicted interaction to be relevant to viral egress at plasma membrane/extracellular matrix	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

HHIP_978 (e-PCR)
- UniSTS:277308

HHIP_V252 (e-PCR)
- UniSTS:277308

SHGC-67731 (e-PCR)
- UniSTS:57689

SHGC-79226 (e-PCR)
- UniSTS:102761

D4S1278 (e-PCR)
- UniSTS:25729

D4S2998 (e-PCR)
- UniSTS:5252

SHGC-59308 (e-PCR)
- UniSTS:6277

SHGC-106691 (e-PCR)
- UniSTS:169981

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables hedgehog family protein binding	IPI Inferred from Physical Interaction more info	PubMed
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 dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
involved_in epithelial tube branching involved in lung morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in neuroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in skeletal system morphogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in ciliary membrane	TAS Traceable Author Statement more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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Preferred Names: hedgehog-interacting protein

NCBI Reference Sequences (RefSeq)

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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.

Genomic

NG_011496.1 RefSeqGene

Range

4976..97709

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_022475.3 → NP_071920.1 hedgehog-interacting protein precursor

See identical proteins and their annotated locations for NP_071920.1

Status: REVIEWED

Source sequence(s)

AC098588, AY009951, BC025311

Consensus CDS

CCDS3762.1

UniProtKB/Swiss-Prot

Q6PK09, Q8NCI7, Q96QV1, Q9BXK3, Q9H1J4, Q9H7E7

UniProtKB/TrEMBL

A8K734

Related

ENSP00000296575.3, ENST00000296575.8

Conserved Domains (2) summary

pfam03024
Location:38 → 220

Folate_rec; Folate receptor family

pfam07995
Location:226 → 428

GSDH; Glucose / Sorbosone dehydrogenase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

144646156..144745271

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005263178.6 → XP_005263235.1 hedgehog-interacting protein isoform X1

UniProtKB/TrEMBL

A8K734

Conserved Domains (2) summary

pfam03024
Location:38 → 220

Folate_rec; Folate receptor family

pfam07995
Location:226 → 428

GSDH; Glucose / Sorbosone dehydrogenase
XM_006714288.5 → XP_006714351.1 hedgehog-interacting protein isoform X2

UniProtKB/TrEMBL

A8K734

Conserved Domains (2) summary

pfam03024
Location:38 → 220

Folate_rec; Folate receptor family

pfam07995
Location:226 → 428

GSDH; Glucose / Sorbosone dehydrogenase