HJV

Chr 1AR

hemojuvelin BMP co-receptor

Also known as: HFE2, HFE2A, JH, RGMC

NCBI Gene: 148738 ENSG00000168509 OMIM: 608374

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]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.881 OMIM phenotype

Clinical Summary— HJV

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Gene-Disease Validity (ClinGen)

hemochromatosis type 2A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

74 unique Pathogenic / Likely Pathogenic· 150 VUS of 467 total submissions

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GeneReview available — HJV

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.004

Z-score 1.89

OE 0.44 (0.24–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.15Z-score

OE missense 1.03 (0.93–1.14)

247 obs / 240.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.44 (0.24–0.88)

0≤0.351.4

Missense OE?1.03 (0.93–1.14)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 6 / 13.5Missense obs/exp: 247 / 240.3Syn Z: 0.43

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38

Likely Pathogenic36

VUS150

Likely Benign219

Benign6

Conflicting18

Pathogenic

Likely Pathogenic

150

VUS

219

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	32	2	4	0	38
Likely Pathogenic	26	10	0	0	36
VUS	3	127	14	6	150
Likely Benign	0	4	26	189	219
Benign	0	1	3	2	6
Conflicting	—				18
Total	61	144	47	197	467

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

73 pathogenic / likely-pathogenic (of 133) ClinVar copy-number / structural variants overlap HJV — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →