REEP1

receptor accessory protein 1, the group of Receptor accessory proteins

Basic information

Region (hg38): 2:86213992-86338083

Previous symbols: [ "C2orf23" ]

Links

ENSG00000068615 ∙ NCBI:65055 ∙ OMIM:609139 ∙ HGNC:25786 ∙ Uniprot:Q9H902 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, type 5B (Limited), mode of inheritance: AD
• hereditary spastic paraplegia 31 (Definitive), mode of inheritance: AD
• hereditary spastic paraplegia 31 (Supportive), mode of inheritance: AD
• neuronopathy, distal hereditary motor, type 5A (Supportive), mode of inheritance: AD
• spinal muscular atrophy, distal, autosomal recessive, 6 (Limited), mode of inheritance: AR
• neuronopathy, distal hereditary motor, type 5B (Strong), mode of inheritance: AD
• hereditary spastic paraplegia 31 (Strong), mode of inheritance: AD
• spinal muscular atrophy, distal, autosomal recessive, 6 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 31, autosomal dominant; Neuronopathy, distal hereditary motor, autosomal dominant 12; Neuronopathy, distal hereditary motor, autosomal recessive 6	AD/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	16826527; 18321925; 19034539; 22703882; 27066569; 31872057; 34193129

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the REEP1 gene.

• Hereditary spastic paraplegia 31 (275 variants)
• not provided (104 variants)
• Inborn genetic diseases (29 variants)
• not specified (20 variants)
• Hereditary spastic paraplegia (19 variants)
• Spastic paraplegia, autosomal dominant (14 variants)
• Neuronopathy, distal hereditary motor, type 5B (11 variants)
• Spastic paraplegia (5 variants)
• Charcot-Marie-Tooth disease (3 variants)
• REEP1-related condition (2 variants)
• Spasticity (1 variants)
• Polyneuropathy (1 variants)
• Hereditary spastic paraplegia 31;Neuronopathy, distal hereditary motor, type 5B (1 variants)
• Spinal muscular atrophy, distal, autosomal recessive, 6 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REEP1 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	30	1	33
missense	3	6	92	2	1	104
nonsense	10	4				14
start loss		1				1
frameshift	16	6	4			26
inframe indel			1			1
splice donor/acceptor (+/-2bp)	9	7				16
splice region	1		12	9		22
non coding	1		43	46	45	135
Total	39	24	142	78	47

Highest pathogenic variant AF is 0.00000657

Variants in REEP1

This is a list of pathogenic ClinVar variants found in the REEP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-86214044-A-G		Hereditary spastic paraplegia 31	Likely benign (Jun 29, 2018)
2-86214072-G-C		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214143-G-A		Hereditary spastic paraplegia 31	Uncertain significance (Jan 12, 2018)
2-86214180-A-C		Hereditary spastic paraplegia 31	Benign (Jun 29, 2018)
2-86214189-A-C		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214211-C-CTGTT		Spastic paraplegia, autosomal dominant	Benign (Jun 29, 2018)
2-86214214-T-G		Hereditary spastic paraplegia 31	Benign (Dec 01, 2021)
2-86214255-C-T		Hereditary spastic paraplegia 31	Benign (Jan 13, 2018)
2-86214273-A-G		Hereditary spastic paraplegia 31	Benign (Apr 27, 2017)
2-86214306-T-G		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214460-A-G		Hereditary spastic paraplegia 31	Likely benign (Apr 27, 2017)
2-86214481-T-C		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214526-C-T		Hereditary spastic paraplegia 31	Likely benign (Mar 03, 2020)
2-86214554-C-T		Hereditary spastic paraplegia 31	Benign (Jan 13, 2018)
2-86214582-C-G		Hereditary spastic paraplegia 31	Benign/Likely benign (Jul 02, 2019)
2-86214605-C-G		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214659-G-A		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214682-T-C		Hereditary spastic paraplegia 31	Uncertain significance (Jan 12, 2018)
2-86214729-G-A		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214839-G-T		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214850-G-T		Hereditary spastic paraplegia 31	Uncertain significance (Jan 13, 2018)
2-86214908-C-T		Hereditary spastic paraplegia 31	Likely benign (Jun 24, 2021)
2-86214988-G-GA		Spastic paraplegia, autosomal dominant	Uncertain significance (Jun 14, 2016)
2-86214989-CA-C			Likely benign (Oct 29, 2020)
2-86214989-C-CA		Spastic paraplegia, autosomal dominant	Benign (Feb 13, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REEP1	protein_coding	protein_coding	ENST00000538924	7	124091

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.986	0.0137	125716	0	1	125717	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	80	122	0.655	0.00000725	1334
Missense in Polyphen		15	33.103	0.45313		374
Synonymous	-0.331	52	49.0	1.06	0.00000341	406
Loss of Function	3.34	0	13.0	0.00	6.47e-7	149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for endoplasmic reticulum (ER) network formation, shaping and remodeling; it links ER tubules to the cytoskeleton. May also enhance the cell surface expression of odorant receptors (PubMed:20200447). May play a role in long-term axonal maintenance (PubMed:24478229). {ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:24478229}.
• Disease: DISEASE: Neuronopathy, distal hereditary motor, 5B (HMN5B) [MIM:614751]: A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN5B is characterized by onset in the first or second decade of distal muscle weakness and atrophy, primarily affecting the intrinsic hand muscles, but also affecting the lower legs, resulting in abnormal gait and pes cavus. {ECO:0000269|PubMed:22703882}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling by GPCR;Signal Transduction;Olfactory Signaling Pathway;G alpha (s) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.107
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.56

Haploinsufficiency Scores

• pHI: 0.442
• hipred: Y
• hipred_score: 0.773
• ghis: 0.431

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0542

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Reep1
• 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); skeleton phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of intracellular transport;protein insertion into membrane;endoplasmic reticulum tubular network organization
• Cellular component: cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane;mitochondrial membrane;endoplasmic reticulum tubular network
• Molecular function: protein binding;microtubule binding;olfactory receptor binding