FRRS1L

ferric chelate reductase 1 like

Basic information

Region (hg38): 9:109130292-109167249

Previous symbols: [ "C9orf4" ]

Links

ENSG00000260230 ∙ NCBI:23732 ∙ OMIM:604574 ∙ HGNC:1362 ∙ Uniprot:Q9P0K9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 37 (Moderate), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 37 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 37	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	27236917; 27239025

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FRRS1L gene.

• Developmental and epileptic encephalopathy, 37 (314 variants)
• not provided (65 variants)
• Inborn genetic diseases (17 variants)
• Chorea;Progressive encephalopathy;Seizure (3 variants)
• See cases (2 variants)
• Seizure;Chorea;Progressive encephalopathy (1 variants)
• Seizure (1 variants)
• FRRS1L-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FRRS1L 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			2	58		60
missense		1	155	2	1	159
nonsense	7	2	1			10
start loss						0
frameshift	8	4				12
inframe indel		1				1
splice donor/acceptor (+/-2bp)		3				3
splice region			2	7	1	10
non coding	1	1	32	36	17	87
Total	16	12	190	96	18

Highest pathogenic variant AF is 0.0000197

Variants in FRRS1L

This is a list of pathogenic ClinVar variants found in the FRRS1L region.

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

Position	Type	Phenotype	Significance	ClinVar
9-109137174-A-G			Benign (Jul 26, 2018)
9-109137458-G-A		Developmental and epileptic encephalopathy, 37	Likely benign (Nov 02, 2023)
9-109137464-T-A		Developmental and epileptic encephalopathy, 37	Likely benign (Jan 24, 2024)
9-109137468-A-T			Uncertain significance (Mar 01, 2018)
9-109137475-G-A		Developmental and epileptic encephalopathy, 37	Likely benign (Jan 05, 2024)
9-109137475-G-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (Aug 12, 2022)
9-109137476-G-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (Mar 18, 2022)
9-109137477-T-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (Aug 16, 2022)
9-109137485-C-T		Developmental and epileptic encephalopathy, 37	Likely benign (Sep 13, 2022)
9-109137486-A-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (May 24, 2020)
9-109137507-C-T		Developmental and epileptic encephalopathy, 37 • Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
9-109137515-A-T		Developmental and epileptic encephalopathy, 37	Likely benign (Apr 03, 2021)
9-109137517-A-T			Uncertain significance (Jan 28, 2020)
9-109137519-G-A		Developmental and epileptic encephalopathy, 37	Uncertain significance (Aug 31, 2021)
9-109137524-G-A		Developmental and epileptic encephalopathy, 37	Likely benign (Nov 01, 2023)
9-109137528-T-G		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
9-109137529-G-A		Developmental and epileptic encephalopathy, 37 • Chorea;Progressive encephalopathy;Seizure	Pathogenic (Mar 14, 2024)
9-109137531-T-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (Feb 25, 2022)
9-109137535-C-T		Developmental and epileptic encephalopathy, 37	Uncertain significance (Aug 09, 2022)
9-109137543-G-A		Developmental and epileptic encephalopathy, 37	Uncertain significance (Jul 19, 2022)
9-109137544-GC-TT		Developmental and epileptic encephalopathy, 37	Uncertain significance (Dec 20, 2021)
9-109137552-A-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (Jul 06, 2022)
9-109137553-T-C		Developmental and epileptic encephalopathy, 37	Uncertain significance (Oct 20, 2018)
9-109137555-T-A		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
9-109137563-C-G		Developmental and epileptic encephalopathy, 37	Uncertain significance (Mar 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FRRS1L	protein_coding	protein_coding	ENST00000561981	5	36999

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00146	0.884	125735	0	10	125745	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.581	121	140	0.862	0.00000748	2147
Missense in Polyphen		26	37.172	0.69944		407
Synonymous	-0.0283	51	50.7	1.00	0.00000269	734
Loss of Function	1.37	6	10.9	0.551	5.20e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000592	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000592	0.0000544
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Important modulator of glutamate signaling pathway. {ECO:0000269|PubMed:27236917}.

Recessive Scores

• pRec: 0.120

Haploinsufficiency Scores

• pHI: 0.203
• hipred: N
• hipred_score: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Frrs1l
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: regulation of postsynaptic membrane neurotransmitter receptor levels;regulation of glutamate receptor signaling pathway
• Cellular component: cellular_component;plasma membrane;integral component of membrane;cell junction;synapse
• Molecular function: molecular_function