RETREG1 (reticulophagy regulator 1)

Gene

• Entrez ID: 54463
• Gene name: Reticulophagy regulator 1
• Gene symbol: RETREG1
• Synonyms (NCBI Gene): FAM134B, JK-1, JK1
• Chromosome: 5
• Chromosome location: 5p15.1
• Summary: The protein encoded by this gene is a cis-Golgi transmembrane protein that may be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Mutations in this gene are a cause of hereditary sensory and autonomic neuropathy type II

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852737	G>A	Pathogenic, uncertain-significance	Stop gained, coding sequence variant, genic upstream transcript variant
rs137852738	A>G	Pathogenic, uncertain-significance	Splice donor variant
rs137852739	G>A,C	Pathogenic-likely-pathogenic, pathogenic, uncertain-significance	Stop gained, coding sequence variant, missense variant
rs143878016	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Coding sequence variant, missense variant
rs767329180	C>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs886037748	T>-	Uncertain-significance, pathogenic	Coding sequence variant, frameshift variant
rs886043753	A>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs941182270	G>A	Pathogenic	Coding sequence variant, stop gained

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000423	Process	Mitophagy	IEA
GO:0005515	Function	Protein binding	IPI	26040720, 32296183, 32814053, 34524948
GO:0005730	Component	Nucleolus	IDA
GO:0005783	Component	Endoplasmic reticulum	IDA	35239449
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IBA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	26040720
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005801	Component	Cis-Golgi network	IEA
GO:0005801	Component	Cis-Golgi network	ISS
GO:0006914	Process	Autophagy	IEA
GO:0006914	Process	Autophagy	IEA
GO:0007029	Process	Endoplasmic reticulum organization	IEA
GO:0016020	Component	Membrane	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0019233	Process	Sensory perception of pain	IMP	19838196
GO:0030574	Process	Collagen catabolic process	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IBA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IMP	26040720
GO:0050872	Process	White fat cell differentiation	IEA
GO:0061709	Process	Reticulophagy	IBA
GO:0061709	Process	Reticulophagy	IEA
GO:0061709	Process	Reticulophagy	IEA
GO:0061709	Process	Reticulophagy	IMP	26040720, 31930741
GO:0061753	Process	Substrate localization to autophagosome	IEA
GO:0140506	Function	Endoplasmic reticulum-autophagosome adaptor activity	IEA

Other IDs

• MIM: 613114
• HGNC: 25964
• e!Ensembl: ENSG00000154153

Protein

• UniProt ID: Q9H6L5
• Protein name: Reticulophagy regulator 1 (Reticulophagy receptor 1)
• Protein function: Endoplasmic reticulum (ER)-anchored autophagy regulator which mediates ER delivery into lysosomes through sequestration into autophagosomes (PubMed:26040720, PubMed:31930741, PubMed:34338405). Promotes membrane remodeling and ER scission via its
• PDB: 7BRQ, 7FB5
• Tissue specificity: TISSUE SPECIFICITY: Overexpressed in esophageal squamous cell carcinoma (PubMed:17487424). {ECO:0000269|PubMed:17487424}.
• Sequence:

  MASPAPPEHAEEGCPAPAAEEQAPPSPPPPQASPAERQQQEEEAQEAGAAEGAGLQVEEA
  AGRAAAAVTWLLGEPVLWLGCRADELLSWKRPLRSLLGFVAANLLFWFLALTPWRVYHLI
  SVMILGRVIMQIIKDMVLSRTRGAQLWRSLSESWEVINSKPDERPRLSHCIAESWMNFSI
  FLQEMSLFKQQSPGKFCLLVCSVCTFFTILGSYIPGVILSYLLLLCAFLCPLFKCNDIGQ
  KIYSKIKSVLLKLDFGIGEYINQKKRERSEADKEKSHKDDSELDFSALCPKISLTVAAKE
  LSVSDTDVSEVSWTDNGTFNLSEGYTPQTDTSDDLDRPSEEVFSRDLSDFPSLENGMGTN
  DEDELSLGLPTELKRKKEQLDSGHRPSKETQSAAGLTLPLNSDQTFHLMSNLAGDVITAA
  VTAAIKDQLEGVQQALSQAAPIPEEDTDTEEGDDFELLDQSELDQIESELGLTQDQEAEA
  QQNKKSSGFLSNLLGGH

• Sequence length: 497

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
Charcot-Marie-Tooth disease	Pathogenic	rs137852739, rs137852737, rs137852736, rs137852738	RCV000789098 RCV000789751 RCV000789750 RCV000789099	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary sensory and autonomic neuropathy type 2	Pathogenic	rs137852739, rs137852737, rs137852736, rs137852738	RCV003447062 RCV003447063 RCV003447085 RCV003447086	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neuropathy, hereditary sensory and autonomic, type 2B	Pathogenic; Likely pathogenic	rs137852739, rs137852737, rs751185980, rs2477809311, rs2477809965, rs137852736, rs137852738, rs1741988534	RCV000000356 RCV000000358 RCV003120332 RCV003316887 RCV003331882 RCV001843420 RCV001843421 RCV001169985	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY MOTOR AND SENSORY-NEUROPATHY TYPE II	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY	—	ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE II	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY SENSORY AUTONOMIC NEUROPATHY, TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY SENSORY AUTONOMIC NEUROPATHY, TYPE 2	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY SENSORY AUTONOMIC NEUROPATHY, TYPE 5	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary spastic paraplegia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuropathy, hereditary sensory and autonomic, type 2A	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIA	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIB	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETREG1-related disorder	Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORY NEUROPATHY, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acro-Osteolysis	Acrosteolysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adenocarcinoma	Adenocarcinoma	BEFREE	24825067, 24973512, 29318692		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of large intestine	Colorectal Cancer	BEFREE	24825067, 24973512		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	24825067, 29318692		★☆☆☆☆ Found in Text Mining only
Adenoma of large intestine	Colorectal adenoma	BEFREE	24825067, 24973512, 29318692		★☆☆☆☆ Found in Text Mining only
Allergic rhinitis (disorder)	Allergic rhinitis	BEFREE	24970562, 29226326		★☆☆☆☆ Found in Text Mining only
Anhidrosis	Anhidrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	28754978	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	24973512		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	37460952	Inhibit	★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	24927874, 24973512, 27120410, 28273937, 29318692, 29964340		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24825067, 24973512, 28144752, 29318692		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	28144752, 32857678	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	28549913	Inhibit	★☆☆☆☆ Found in Text Mining only
Dementia, Vascular	Dementia	BEFREE	21127458		★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	BEFREE	31475481		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	27373372	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	27373372	Associate	★☆☆☆☆ Found in Text Mining only
Gastroesophageal reflux disease	Gastroesophageal Reflux Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Motor and Sensory-Neuropathy Type II	Dysautonomia	GENOMICS_ENGLAND_DG	19838196		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory and Autonomic Neuropathies	Hereditary sensory and autonomic neuropathy	GENOMICS_ENGLAND_DG	19838196, 24327336		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory and Autonomic Neuropathies	Hereditary sensory and autonomic neuropathy	CTD_human_DG	19838196		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory and Autonomic Neuropathies	Hereditary sensory and autonomic neuropathy	Pubtator	21115472, 21820098, 31475481, 31930741, 35332675	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory and Autonomic Neuropathies	Hereditary sensory and autonomic neuropathy	BEFREE	29226326, 31475481		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary sensory and autonomic neuropathy type 2	Hereditary Sensory And Autonomic Neuropathy	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary Sensory Autonomic Neuropathy, Type 1	Hereditary sensory and autonomic neuropathy	CTD_human_DG	19838196		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory Autonomic Neuropathy, Type 2	Hereditary sensory and autonomic neuropathy	CTD_human_DG	19838196		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory Autonomic Neuropathy, Type 2	Hereditary sensory and autonomic neuropathy	BEFREE	21820098		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory Autonomic Neuropathy, Type 2	Hereditary sensory and autonomic neuropathy	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory Autonomic Neuropathy, Type 5	Hereditary sensory and autonomic neuropathy	CTD_human_DG	19838196		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary Sensory Radicular Neuropathy	Hereditary sensory and autonomic neuropathy	CTD_human_DG	19838196		★☆☆☆☆ Found in Text Mining only
HSAN Type IV	Hereditary insensitivity to pain with anhidrosis	CTD_human_DG	19838196		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	34394825	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	35332675	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30556279		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	28688308		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24825067, 27120410, 27373372, 28144752, 28688308, 29226326, 29964340		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	24927874, 24973512, 27120410, 28273937, 29318692, 29964340		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	30381879		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24973512, 27120410, 28144752, 28549913, 29226326, 29318692, 30291780, 30556279, 30794892, 31446166		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	27373372		★☆☆☆☆ Found in Text Mining only
Neuropathy, Hereditary Sensory And Autonomic, Type IIA	Neuropathy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuropathy, Hereditary Sensory And Autonomic, Type IIB	Neuropathy	GENOMICS_ENGLAND_DG	19838196, 24327336		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuropathy, Hereditary Sensory And Autonomic, Type IIB	Neuropathy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuropathy, Hereditary Sensory And Autonomic, Type IIB	Neuropathy	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	BEFREE	31446166		★☆☆☆☆ Found in Text Mining only
Osteomyelitis	Osteomyelitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paronychia Inflammation	Paronychia Inflammation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral axonal neuropathy	Peripheral axonal neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rhinitis Allergic	Rhinitis	Pubtator	24970562	Associate	★☆☆☆☆ Found in Text Mining only
Sensory Neuropathy, Hereditary	Sensory Neuropathy, Hereditary	CTD_human_DG	19838196		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma	Carcinoma	LHGDN	17487424		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	27373372, 29226326, 30556279, 30794892		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of skin	Skin carcinoma	BEFREE	30867688		★☆☆☆☆ Found in Text Mining only