RETREG1

reticulophagy regulator 1

Basic information

Region (hg38): 5:16473038-16617101

Previous symbols: [ "FAM134B" ]

Links

ENSG00000154153 ∙ NCBI:54463 ∙ OMIM:613114 ∙ HGNC:25964 ∙ Uniprot:Q9H6L5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary sensory and autonomic neuropathy type 2 (Supportive), mode of inheritance: AR
• neuropathy, hereditary sensory and autonomic, type 2B (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory and autonomic, type IIB	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	19838196; 24327336
Insensitivity to pain can result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RETREG1 gene.

• not provided (15 variants)
• Neuropathy, hereditary sensory and autonomic, type 2B (5 variants)
• Hereditary sensory and autonomic neuropathy type 2 (3 variants)
• Charcot-Marie-Tooth disease (3 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RETREG1 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			1	82	4	87
missense			203	3	1	207
nonsense	9	1	2			12
start loss			1			1
frameshift	6		2			8
inframe indel			11			11
splice donor/acceptor (+/-2bp)	1	3				4
splice region			7	9		16
non coding			19	47	32	98
Total	16	4	239	132	37

Highest pathogenic variant AF is 0.00000659

Variants in RETREG1

This is a list of pathogenic ClinVar variants found in the RETREG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-16473088-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16473100-T-C		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16473404-T-G		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16473506-A-G		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 12, 2018)
5-16473571-T-C		Neuropathy, hereditary sensory and autonomic, type 2B	Likely benign (Jan 13, 2018)
5-16473572-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (May 17, 2018)
5-16473581-A-G		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16473706-A-G		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 12, 2018)
5-16473715-A-G		Neuropathy, hereditary sensory and autonomic, type 2B	Likely benign (Jan 12, 2018)
5-16473729-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Benign (Jan 12, 2018)
5-16473828-C-A		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 12, 2018)
5-16473888-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 12, 2018)
5-16473984-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16474149-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Benign (Jan 13, 2018)
5-16474160-A-G		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 12, 2018)
5-16474231-T-A		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16474243-C-T		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16474285-G-GA		Hereditary sensory and autonomic neuropathy type 2	Benign (Jun 14, 2016)
5-16474506-G-T		Neuropathy, hereditary sensory and autonomic, type 2B	Benign (Jan 13, 2018)
5-16474522-T-C		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 12, 2018)
5-16474535-T-G		Neuropathy, hereditary sensory and autonomic, type 2B	Benign (Jun 26, 2018)
5-16474618-A-C		Neuropathy, hereditary sensory and autonomic, type 2B	Uncertain significance (Jan 13, 2018)
5-16474669-CT-C			Likely benign (Aug 21, 2019)
5-16474669-C-CT		Hereditary sensory and autonomic neuropathy type 2	Benign (Aug 10, 2019)
5-16474669-C-CTT			Likely benign (Aug 10, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RETREG1	protein_coding	protein_coding	ENST00000306320	9	144021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000636	0.976	124770	0	24	124794	0.0000962

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.597	214	240	0.891	0.0000112	3233
Missense in Polyphen		60	81.851	0.73304		1167
Synonymous	0.272	90	93.3	0.964	0.00000452	960
Loss of Function	2.06	12	22.5	0.533	0.00000104	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000369	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.0000619	0.0000618
Middle Eastern	0.000167	0.000167
South Asian	0.000131	0.000131
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endoplasmic reticulum-anchored autophagy receptor that mediates ER delivery into lysosomes through sequestration into autophagosomes (PubMed:26040720). Promotes membrane remodeling and ER scission via its membrane bending capacity and targets the fragments into autophagosomes via interaction with ATG8 family proteins (PubMed:26040720). Required for long-term survival of nociceptive and autonomic ganglion neurons (PubMed:19838196, PubMed:26040720). {ECO:0000269|PubMed:19838196, ECO:0000269|PubMed:26040720}.
• Disease: DISEASE: Neuropathy, hereditary sensory and autonomic, 2B (HSAN2B) [MIM:613115]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2B is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation. Onset occurs in the first or second decade, with impaired nociception and progressive mutilating ulceration of the hands and feet with osteomyelitis and acroosteolysis. Amputations of the hands and feet are common. Autonomic dysfunction includes hyperhidrosis, urinary incontinence, and slow pupillary light response. {ECO:0000269|PubMed:19838196}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.109

Intolerance Scores

• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.15

Haploinsufficiency Scores

• pHI: 0.678
• hipred: N
• hipred_score: 0.384
• ghis: 0.434

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Retreg1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: sensory perception of pain;negative regulation of neuron apoptotic process;reticulophagy
• Cellular component: nucleolus;endoplasmic reticulum;cis-Golgi network;nuclear body;integral component of endoplasmic reticulum membrane
• Molecular function: protein binding