HJV

hemojuvelin BMP co-receptor, the group of Repulsive guidance molecule family

Basic information

Region (hg38): 1:146017467-146036746

Previous symbols: [ "HFE2" ]

Links

ENSG00000168509 ∙ NCBI:148738 ∙ OMIM:608374 ∙ HGNC:4887 ∙ Uniprot:Q6ZVN8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemochromatosis type 2A (Strong), mode of inheritance: AR
• hemochromatosis type 2 (Supportive), mode of inheritance: AR
• hemochromatosis type 2A (Definitive), mode of inheritance: AR
• hemochromatosis type 2A (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemochromatosis, type 2A	AR	Biochemical; Gastrointestinal; Hematologic	Patients may benefit from surveillance related to iron overload, and from interventions such as venesection; Certain agents should be avoided (eg, alcohol consumption; iron-containing compounds; uncooked seafood); Hormone therapy may be beneficial in order to prevent osteoporosis	Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	10205270; 12891378; 14982873; 15254010; 14982867; 14647275; 15461631; 15811010; 17847004; 18492090; 19796184; 20301349
Variants may also modify the severity of HFE-related hemochromatosis

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HJV gene.

• not provided (252 variants)
• Hemochromatosis type 2A (73 variants)
• Inborn genetic diseases (6 variants)
• HJV-related condition (3 variants)
• Juvenile hemochromatosis (3 variants)
• not specified (2 variants)
• Hemochromatosis type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HJV gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	137	2	143
missense	5	4	52	2	1	64
nonsense	8	1	1			10
start loss		2				2
frameshift	20	2				22
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)	1	3				4
splice region				5	1	6
non coding	2	1	13	11	2	29
Total	36	13	73	151	5

Highest pathogenic variant AF is 0.000256

Variants in HJV

This is a list of pathogenic ClinVar variants found in the HJV region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-146017503-T-A		Hemochromatosis type 2A	Uncertain significance (Jan 12, 2018)
1-146017705-T-C		Hemochromatosis type 2A	Uncertain significance (Jan 15, 2018)
1-146017789-T-G		Hemochromatosis type 2A	Uncertain significance (Jan 13, 2018)
1-146017879-C-T		Hemochromatosis type 2A	Uncertain significance (Jan 13, 2018)
1-146017880-C-T		Hemochromatosis type 2A	Uncertain significance (Jan 12, 2018)
1-146017887-C-T		Hemochromatosis type 2A	Uncertain significance (Jan 12, 2018)
1-146018083-A-G			Likely benign (May 30, 2023)
1-146018092-C-T			Uncertain significance (Jul 13, 2020)
1-146018094-A-G			Uncertain significance (Jun 18, 2015)
1-146018098-A-G			Likely benign (Jan 16, 2024)
1-146018101-A-C		Hemochromatosis type 2A	Uncertain significance (Sep 01, 2021)
1-146018104-G-C		Hemochromatosis type 2A	Uncertain significance (Jan 13, 2018)
1-146018110-A-G			Likely benign (Jul 16, 2023)
1-146018120-G-A		Hemochromatosis type 2A	Uncertain significance (Jul 14, 2021)
1-146018131-G-A			Likely benign (Sep 29, 2023)
1-146018131-G-T			Likely benign (Nov 15, 2023)
1-146018152-C-A			Likely benign (Nov 30, 2022)
1-146018152-C-T			Likely benign (Jun 22, 2021)
1-146018161-T-C			Likely benign (Dec 23, 2022)
1-146018164-G-C			Likely benign (Aug 01, 2021)
1-146018167-G-A			Likely benign (Jul 28, 2023)
1-146018170-G-C			Likely benign (Jul 25, 2022)
1-146018176-C-T			Likely benign (Jun 23, 2022)
1-146018180-T-C		not specified	Uncertain significance (Apr 20, 2023)
1-146018182-C-T			Likely benign (Aug 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HJV	protein_coding	protein_coding	ENST00000336751	3	4451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00424	0.965	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.152	247	240	1.03	0.0000131	2710
Missense in Polyphen		98	94.673	1.0351		1158
Synonymous	0.430	92	97.4	0.945	0.00000497	973
Loss of Function	1.89	6	13.5	0.445	9.27e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000125	0.000123
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis. {ECO:0000250|UniProtKB:Q7TQ32}.
• Disease: DISEASE: Hemochromatosis 2A (HFE2A) [MIM:602390]: A juvenile form of hemochromatosis, a disorder of iron metabolism with excess deposition of iron in a variety of organs leading to their failure, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of juvenile hemochromatosis at presentation are hypogonadism and cardiomyopathy. {ECO:0000269|PubMed:14647275, ECO:0000269|PubMed:14982867, ECO:0000269|PubMed:14982873, ECO:0000269|PubMed:15461631}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hfe effect on hepcidin production;Developmental Biology;BMP receptor signaling;Netrin-1 signaling;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.239

Intolerance Scores

• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.56

Haploinsufficiency Scores

• pHI: 0.826
• hipred: Y
• hipred_score: 0.525
• ghis: 0.530

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Hfe2
• Phenotype: immune system phenotype; renal/urinary system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: hjv
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: undulate

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cellular iron ion homeostasis;protein autoprocessing;BMP signaling pathway;negative regulation of BMP signaling pathway;activin receptor signaling pathway;positive regulation of transcription by RNA polymerase II;iron ion homeostasis;cellular response to BMP stimulus
• Cellular component: extracellular space;plasma membrane;cell surface;anchored component of membrane;BMP receptor complex;plasma membrane protein complex;HFE-transferrin receptor complex
• Molecular function: signaling receptor binding;protein binding;coreceptor activity;BMP binding;BMP receptor activity;transferrin receptor binding