Iron metabolism disorders - NOT common HFE mutations

Gene: CYBRD1

Red List (low evidence)

The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 5:40 p.m. | Last Modified: 10 Dec 2025, 5:40 p.m.

Panel Version: 3.3

Red List (low evidence)

It would appear that there are no CYBRD1 rare SNVs associated with iron metabolism.  However, PMID: 37632052 concludes that the coexistence of minor alleles of HDAC3 rs976552 and CYBRD1 rs884409 is linked with higher prevalence of hepatocellular carcinoma.

Furthermore, HFE p.C282Y variant together with the CYBRD1 polymorphism rs884409 reduces CYBRD1 promoter activity by 30% (PMID: 19673882).

Overall, there is insufficient evidence for CYBRD1 to be green on PanelApp.

Created: 15 Apr 2024, 4:48 p.m. | Last Modified: 17 Dec 2024, 1:55 p.m.

Panel Version: 2.12

Comment on phenotypes: There is no OMIM, MONDO or ORPHANET disease association to this gene. The term hereditary hemochromatosis MONDO:0006507 was chosen as it represent the general disease described in the limited literature associated with this gene.

Created: 2 Mar 2021, 5:17 p.m. | Last Modified: 2 Mar 2021, 5:17 p.m.

Panel Version: 1.11

Red List (low evidence)

Paucity of publications. Please note one of the variants reported in PMID 15338274, p.Arg226His is present in over 1,000 hets in gnomad.

Created: 22 Jan 2021, 7:33 a.m. | Last Modified: 22 Jan 2021, 7:33 a.m.

Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Iron overload

Publications

• 15338274

Green List (high evidence)

Green List (high evidence)

Green List (high evidence)

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group.

Created: 18 Feb 2019, 11:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
NA IRON OVERLOAD

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.

Created: 13 Feb 2019, 12:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
N/A Primary iron overload

Publications

• 15338274

I don't know

Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green

Created: 28 May 2019, 2:08 p.m.

New review/rating by Frances Smith, Viapath Kings College Hospital (Curation_Template_GMS_Haem_FS_updated_reviews_20190425.xlsx) on behalf of London South GLH for the GMS Haematology specialist test group. Gene rated as Green.

Created: 4 May 2019, 8:55 p.m.

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: CYBRD1; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: NA IRON OVERLOAD; PMID(s): none submitted

Created: 18 Feb 2019, 11:49 a.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: CYBRD1; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: N/A Primary iron overload; PMID(s): 15338274

Created: 13 Feb 2019, 12:39 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: CYBRD1; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: none submitted; PMID(s): 15338274; 27884173

Created: 5 Feb 2019, 5:51 p.m.

Green List (high evidence)

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

3 independent reports where 3 probands had an iron overload phenotype

Created: 5 Feb 2019, 5:50 p.m.