CYBRD1

protein-coding

cytochrome b reductase 1, the group of Cytochrome b561

Gene summary

This gene is a member of the cytochrome b(561) family that encodes an iron-regulated protein. It highly expressed in the duodenal brush border membrane. It has ferric reductase activity and is believed to play a physiological role in dietary iron absorption. [provided by RefSeq, Jul 2008]

MANE transcript

NM_024843.4

Inheritance

ClinVar variants

U:31B:7

Top phenotype

hereditary hemochromatosis

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr2:171,522,247-171,558,129

External References & Databases

Ensembl (ENSG00000071967)

Transcript & Mutation Effects

hg38 • Region Span ~35.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary hemochromatosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0006507

Submitter: Genomics England PanelApp

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYBRD1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

CYBRD1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024843.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar		5
missense			29 clinvar	3 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	31	7	0	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024843.4	RefSeq	NP_079119.3	4	MANE Select
ENST00000321348.9	Ensembl	ENSP00000319141.4	4	MANE Select
NM_001127383.2	RefSeq	NP_001120855.1	3	Standard
NM_001256909.2	RefSeq	NP_001243838.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mineral absorption - Homo sapiens (human)
Transport of small molecules
Iron uptake and transport

Biological Process

cellular iron ion homeostasis
response to iron ion
oxidation-reduction process

Molecular Function

ferric-chelate reductase activity
protein binding
oxidoreductase activity
oxidoreductase activity, oxidizing metal ions
metal ion binding

Cellular Component

lysosomal membrane
plasma membrane
integral component of membrane
brush border membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321348
Coding exons: 4
Length: 35887
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125732
p: 0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.589	139	160	0.869	0.00000787	1838
Missense (PolyPhen)		37	54.41	0.68002		635
Synonymous	-0.924	75	65.5	1.15	0.00000357	597
Loss of Function	1.83	5	11.8	0.424	5.92e-7	122

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ferric-chelate reductase that reduces Fe(3+) to Fe(2+). Present at the brush border of duodenal enterocytes where it probably reduces dietary Fe(3+) thereby facilitating its transport into the mucosal cells. Uses ascorbate as electron donor. May be involved in extracellular ascorbate recycling in erythrocyte membranes. May also act as a ferrireductase in airway epithelial cells. {ECO:0000269|PubMed:16521311, ECO:0000269|PubMed:16521312, ECO:0000269|PubMed:17068337, ECO:0000269|PubMed:19673882}.;

Recessive Scores

pRec: 0.183

Intolerance Scores

LoFtool: 0.317
RVIS EVS: 0.68
RVIS percentile EVS: 84.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.200

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium