FRRS1

protein-coding

ferric chelate reductase 1

Gene summary

Members of the cytochrome b561 (CYB561; MIM 600019) family, including FRRS1, reduce ferric to ferrous iron before its transport from the endosome to the cytoplasm (Vargas et al., 2003 [PubMed 14499595]).[supplied by OMIM, Mar 2008]

Previous symbols:

SDFR2

MANE transcript

NM_001361041.2

Inheritance

—

ClinVar variants

U:83B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr1:99,703,970-99,766,635

External References & Databases

Ensembl (ENSG00000156869)

Transcript & Mutation Effects

hg38 • Region Span ~62.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FRRS1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 85

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001361041.2. 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			4 clinvar			4
missense			78 clinvar	3 clinvar		81
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	83	3	0	86

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001361041.2	RefSeq	NP_001347970.1	15	MANE Select
ENST00000646001.2	Ensembl	ENSP00000496583.2	15	MANE Select
NM_001013660.4	RefSeq	NP_001013682.2	15	Standard
ENST00000287474.10	Ensembl	ENSP00000287474.4	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

oxidation-reduction process

Molecular Function

ferric-chelate reductase activity
metal ion binding

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287474
Coding exons: 15
Length: 57929
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125748
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.570	306	335	0.912	0.0000160	4114
Missense (PolyPhen)		99	107.73	0.91893		1314
Synonymous	-0.0702	116	115	1.01	0.00000596	1172
Loss of Function	2.24	19	32.9	0.578	0.00000155	385

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00026	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ferric-chelate reductases reduce Fe(3+) to Fe(2+) before its transport from the endosome to the cytoplasm. {ECO:0000250}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.244
RVIS EVS: -0.11
RVIS percentile EVS: 45.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0630

Gene Damage Prediction

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