HJV hemojuvelin BMP co-receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: HJVprovided by HGNC
Official Full Name: hemojuvelin BMP co-receptorprovided by HGNC
Primary source: HGNC:HGNC:4887
See related: Ensembl:ENSG00000168509 MIM:608374; AllianceGenome:HGNC:4887
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: JH; HFE2; RGMC; HFE2A
Summary: The product of this gene is involved in iron metabolism. It may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression. It could also represent the cellular receptor for hepcidin. Two uORFs in the 5' UTR negatively regulate the expression and activity of the encoded protein. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Defects in this gene are the cause of hemochromatosis type 2A, also called juvenile hemochromatosis (JH). JH is an early-onset autosomal recessive disorder due to severe iron overload resulting in hypogonadotrophic hypogonadism, hepatic fibrosis or cirrhosis and cardiomyopathy, occurring typically before age of 30. [provided by RefSeq, Oct 2015]
Expression: Biased expression in liver (RPKM 40.4), heart (RPKM 17.1) and 2 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 1q21.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (146017470..146021735, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (145134353..145138618, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (145413278..145417543)

Chromosome 1 - NC_000001.11 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
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?

New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis.
Title: New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis.
Estimates of West African Ancestry in African Americans Using Alleles of Iron-Related Genes HJV, SLC40A1, and TFR2.
Title: Estimates of West African Ancestry in African Americans Using Alleles of Iron-Related Genes HJV, SLC40A1, and TFR2.
The functional role of hemojuvelin in acute ischemic stroke.
Title: The functional role of hemojuvelin in acute ischemic stroke.
HJV was significantly downregulated in the muscles of Duchenne muscular dystrophy patients as well as in those of aged humans.
Title: Hemojuvelin is a novel suppressor for Duchenne muscular dystrophy and age-related muscle wasting.
Compound heterozygous mutations of HJV or combined heterozygous mutations of BMP/SMAD pathway genes, marked by HJV variants in the signal peptide region, may represent a novel aetiological factor for Hereditary haemochromatosis (HH).
Title: Non-HFE mutations in haemochromatosis in China: combination of heterozygous mutations involving HJV signal peptide variants.
mild phenotype and late onset are possible in HJV hemochromatosis
Title: Variable expressivity of HJV related hemochromatosis: "Juvenile" hemochromatosis?
Urinary HJV differentiated patients with/without acute kidney injury (AKI), advanced AKI or composite outcome after surgery.
Title: Hemojuvelin Predicts Acute Kidney Injury and Poor Outcomes Following Cardiac Surgery.
Soluble haemojuvelin levels seem to be associated with iron overload parameters and hepcidin levels in hepatitis C virus positive hemodialysis patients.
Title: Relationship of serum haemojuvelin and hepcidin levels with iron level and erythropoietin requirement in prevalent hepatitis C virus positive haemodialysis patients.
HJV increases hepcidin expression in cells transfected with mutant ALK2. Thus, although the BMP pathway is inhibited when normal MT2 cleaves HJV, in the presence of both ALK2wt and mutant ALK2, the heterozygosity for the inactive MT2I212T may leave enough membrane HJV to allow persistent hepcidin activation.
Title: A new form of IRIDA due to combined heterozygous mutations of TMPRSS6 and ACVR1A encoding the BMP receptor ALK2.
Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans
Title: The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.

Submit: New GeneRIF Correction See all GeneRIFs (69)

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
Hemochromatosis type 2A MedGen: C1865614 OMIM: 602390 GeneReviews: Juvenile Hemochromatosis	Compare labs

EBI GWAS Catalog

Description
Two-marker association tests yield new disease associations for coronary artery disease and hypertension. 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

SHGC-33871 (e-PCR)
- UniSTS:17153

G20291 (e-PCR)
- UniSTS:81047

A005K39 (e-PCR)
- UniSTS:81048

Bdab5d06 (e-PCR)
- UniSTS:46258

RH17510 (e-PCR)
- UniSTS:77566

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables BMP binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to BMP receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables coreceptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables coreceptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in BMP signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activin receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to BMP stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular iron ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within multicellular organismal-level iron ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within multicellular organismal-level iron ion homeostasis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autoprocessing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of BMP receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of HFE-transferrin receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of plasma membrane protein complex	IDA Inferred from Direct Assay more info	PubMed
located_in side of membrane	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: hemojuvelin

Names: RGM domain family member C; haemojuvelin; hemochromatosis type 2 (juvenile); hemochromatosis type 2 protein; hemojuvelin BMP coreceptor; repulsive guidance molecule c

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.

Genomic

NG_011568.2 RefSeqGene

Range

5000..9265

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001316767.2 → NP_001303696.1 hemojuvelin isoform c

Status: REVIEWED

Source sequence(s)

BC017926, BC085604, DA893500

Consensus CDS

CCDS72877.1

UniProtKB/Swiss-Prot

Q6ZVN8

Conserved Domains (1) summary

pfam06534
Location:4 → 163

RGM_C; Repulsive guidance molecule (RGM) C-terminus
NM_001379352.1 → NP_001366281.1 hemojuvelin isoform a precursor

Status: REVIEWED

Source sequence(s)

AC243547

Consensus CDS

CCDS72879.1

UniProtKB/Swiss-Prot

B1ALI7, Q2PQ63, Q6IMF6, Q6ZVN8, Q8NAH2, Q8WVJ5

UniProtKB/TrEMBL

A8K9M7

Conserved Domains (2) summary

pfam06534
Location:230 → 389

RGM_C; Repulsive guidance molecule (RGM) C-terminus

pfam06535
Location:37 → 225

RGM_N; Repulsive guidance molecule (RGM) N-terminus
NM_145277.5 → NP_660320.3 hemojuvelin isoform b

See identical proteins and their annotated locations for NP_660320.3

Status: REVIEWED

Source sequence(s)

AK124273, BC085604, DB035674

Consensus CDS

CCDS72878.1

UniProtKB/TrEMBL

A8K466

Related

ENSP00000350495.5, ENST00000357836.5

Conserved Domains (2) summary

pfam06534
Location:117 → 281

RGM_C; Repulsive guidance molecule (RGM) C-terminus

pfam06535
Location:1 → 112

RGM_N; Repulsive guidance molecule (RGM) N-terminus
NM_202004.4 → NP_973733.1 hemojuvelin isoform c

See identical proteins and their annotated locations for NP_973733.1

Status: REVIEWED

Source sequence(s)

AK124273, BC017926, BC085604, DB035674

Consensus CDS

CCDS72877.1

UniProtKB/Swiss-Prot

Q6ZVN8

Related

ENSP00000421820.1, ENST00000497365.5

Conserved Domains (1) summary

pfam06534
Location:4 → 163

RGM_C; Repulsive guidance molecule (RGM) C-terminus
NM_213652.4 → NP_998817.1 hemojuvelin isoform c

See identical proteins and their annotated locations for NP_998817.1

Status: REVIEWED

Source sequence(s)

AK124273, BC085604, DB035674

Consensus CDS

CCDS72877.1

UniProtKB/Swiss-Prot

Q6ZVN8

Related

ENSP00000425716.1, ENST00000475797.1

Conserved Domains (1) summary

pfam06534
Location:4 → 163

RGM_C; Repulsive guidance molecule (RGM) C-terminus
NM_213653.4 → NP_998818.1 hemojuvelin isoform a precursor

See identical proteins and their annotated locations for NP_998818.1

Status: REVIEWED

Source sequence(s)

AC243547

Consensus CDS

CCDS72879.1

UniProtKB/Swiss-Prot

B1ALI7, Q2PQ63, Q6IMF6, Q6ZVN8, Q8NAH2, Q8WVJ5

UniProtKB/TrEMBL

A8K9M7

Related

ENSP00000337014.5, ENST00000336751.11

Conserved Domains (2) summary

pfam06534
Location:230 → 389

RGM_C; Repulsive guidance molecule (RGM) C-terminus

pfam06535
Location:37 → 225

RGM_N; Repulsive guidance molecule (RGM) N-terminus