FRRS1L (ferric chelate reductase 1 like)

Gene

• Entrez ID: 23732
• Gene name: Ferric chelate reductase 1 like
• Gene symbol: FRRS1L
• Synonyms (NCBI Gene): C9orf4, CG-6, CG6, DEE37, EIEE37
• Chromosome: 9
• Chromosome location: 9q31.3
• Summary: This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs779716535	G>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained
rs878853280	G>A	Pathogenic	Coding sequence variant, stop gained
rs878853281	C>T	Pathogenic	Coding sequence variant, stop gained
rs878853282	CCT>-	Likely-pathogenic, pathogenic	Coding sequence variant, inframe deletion
rs878853283	->T	Pathogenic	Coding sequence variant, frameshift variant
rs933379958	C>-,CC	Pathogenic	Frameshift variant, coding sequence variant, upstream transcript variant, genic upstream transcript variant
rs1054228594	G>A	Pathogenic	Coding sequence variant, stop gained
rs1310777849	C>A	Likely-pathogenic	Genic upstream transcript variant, 5 prime UTR variant, upstream transcript variant
rs1564229174	G>A	Pathogenic	Stop gained, coding sequence variant
rs1564229228	T>C	Likely-pathogenic	Splice acceptor variant
rs1564232243	CA>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT715860	hsa-miR-329-5p	HITS-CLIP	19536157
MIRT715859	hsa-miR-4423-3p	HITS-CLIP	19536157
MIRT658067	hsa-miR-500a-5p	HITS-CLIP	23824327
MIRT658066	hsa-miR-501-5p	HITS-CLIP	23824327
MIRT658065	hsa-miR-665	HITS-CLIP	23824327
MIRT658064	hsa-miR-1283	HITS-CLIP	23824327
MIRT715860	hsa-miR-329-5p	HITS-CLIP	19536157
MIRT715859	hsa-miR-4423-3p	HITS-CLIP	19536157
MIRT658067	hsa-miR-500a-5p	HITS-CLIP	23824327
MIRT658066	hsa-miR-501-5p	HITS-CLIP	23824327
MIRT658065	hsa-miR-665	HITS-CLIP	23824327
MIRT658064	hsa-miR-1283	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045202	Component	Synapse	IEA
GO:0045505	Function	Dynein intermediate chain binding	IEA
GO:0051966	Process	Regulation of synaptic transmission, glutamatergic	IEA
GO:0098794	Component	Postsynapse	IEA
GO:0099072	Process	Regulation of postsynaptic membrane neurotransmitter receptor levels	IBA
GO:0099072	Process	Regulation of postsynaptic membrane neurotransmitter receptor levels	IEA
GO:1900449	Process	Regulation of glutamate receptor signaling pathway	IBA
GO:1900449	Process	Regulation of glutamate receptor signaling pathway	IEA
GO:1900449	Process	Regulation of glutamate receptor signaling pathway	IMP	27236917
GO:1904717	Process	Regulation of AMPA glutamate receptor clustering	IEA

Other IDs

• MIM: 604574
• HGNC: 1362
• e!Ensembl: ENSG00000260230

Protein

• UniProt ID: Q9P0K9
• Protein name: DOMON domain-containing protein FRRS1L (Brain protein CG-6) (Ferric-chelate reductase 1-like protein)
• Protein function: Important modulator of glutamate signaling pathway.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03351	DOMON	168 → 283	DOMON domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in adult and fetal brain. Very weak expression in medulla, spinal cord and in adult ovary. {ECO:0000269|PubMed:10603000}.
• Sequence:

  MRRPRQGGGGAGGSAAARARAGGLGGGSVPARARGAPAAARAAWLRDLCARMARPPRQHP
  GVWASLLLLLLTGPAACAASPADDGAGPGGRGPRGRARGDTGADEAVPRHDSSYGTFAGE
  FYDLRYLSEEGYPFPTAPPVDPFAKIKVDDCGKTKGCFRYGKPGCNAETCDYFLSYRMIG
  ADVEFELSADTDGWVAVGFSSDKKMGGDDVMACVHDDNGRVRIQHFYNVGQWAKEIQRNP
  ARDEEGVFENNRVTCRFKRPVNVPRDETIVDLHLSWYYLFAWGPAIQGSITRHDIDSPPA
  SERVVSIYKYEDIFMPSAAYQTFSSPFCLLLIVALTFYLLMGTP

• Sequence length: 344

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Chorea	Pathogenic; Likely pathogenic	rs878853280, rs878853281, rs878853282, rs878853283	RCV000239395 RCV000239392 RCV000239394 RCV000239396	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Developmental and epileptic encephalopathy, 37	Pathogenic; Likely pathogenic	rs2118467700, rs1831184766, rs776257401, rs1285856108, rs2118467979, rs1382335133, rs2118524756, rs1382090523, rs2538503118, rs878853280, rs878853281, rs878853282, rs878853283, rs2538516016, rs2538497130, rs1052826149, rs2538503024, rs933379958, rs1054228594, rs779716535, rs1564232243, rs1564229228, rs1564229174, rs1310777849, rs1035742818, rs747737869, rs1831307625, rs1831271059	RCV001390258 RCV001383854 RCV001382940 RCV001386199 RCV001999815 RCV001945766 RCV001964674 RCV001956306 RCV006249825 RCV002807215 RCV000225353 RCV000225178 RCV000225276 RCV000225128 RCV003025900 RCV003145723 RCV003592483 RCV003592570 RCV003592659 RCV003593309 RCV000554924 RCV000545306 RCV000698199 RCV000689869 RCV000691230 RCV000816811 RCV003591824 RCV001223290 RCV001224897 RCV001203910 RCV001264814	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
FRRS1L-related disorder	Likely pathogenic; Pathogenic	rs878853282, rs1054228594	RCV004755810 RCV003409827	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive encephalopathy	Pathogenic; Likely pathogenic	rs878853280, rs878853281, rs878853282, rs878853283	RCV000239395 RCV000239392 RCV000239394 RCV000239396	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seizure	Pathogenic; Likely pathogenic	rs878853280, rs878853281, rs878853282, rs878853283	RCV000239395 RCV000239392 RCV000239394 RCV000239396	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONTINUOUS SPIKE AND WAVE DURING SLOW WAVE SLEEP SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY	—	ClinGen	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 37	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY WITH SPIKE-WAVE ACTIVATION IN SLEEP	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY WITH SUPPRESSION BURSTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENETIC DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	30692144		★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brain Diseases	Brain disease	Pubtator	32928027	Associate	★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	32928027	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Choreoathetosis	Choreoathetosis	BEFREE	27236917, 30692144		★☆☆☆☆ Found in Text Mining only
Choreoathetosis	Choreoathetosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Choreoathetosis Hypothyroidism And Neonatal Respiratory Distress	Choreoathetosis	Pubtator	27236917	Associate	★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	30692144		★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	32928027	Associate	★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	27236917, 30692144		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	27236917, 29276473		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	27236917, 32928027	Associate	★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 37	Epileptic encephalopathy	CLINVAR_DG	27236917, 27239025, 30525197		★☆☆☆☆ Found in Text Mining only
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 37	Epileptic encephalopathy	GENOMICS_ENGLAND_DG	27239025, 30914295		★☆☆☆☆ Found in Text Mining only
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 37	Epileptic encephalopathy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperkinesis	Hyperkinesia	Pubtator	32928027	Associate	★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	28675162, 30692144		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement disorder	Pubtator	32928027	Associate	★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	27236917		★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	BEFREE	28675162		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spasms Infantile	Infantile spasms	Pubtator	32928027	Associate	★☆☆☆☆ Found in Text Mining only
Speech Delay	Speech Delay	BEFREE	28675162		★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only