REEP6

receptor accessory protein 6, the group of Receptor accessory proteins

Basic information

Region (hg38): 19:1491166-1497927

Previous symbols: [ "C19orf32" ]

Links

ENSG00000115255 ∙ NCBI:92840 ∙ OMIM:609346 ∙ HGNC:30078 ∙ Uniprot:Q96HR9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 77 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 77	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	Ophthalmologic	27889058

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the REEP6 gene.

• not provided (10 variants)
• Retinitis pigmentosa 77 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REEP6 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				51	3	54
missense		1	100	2	3	106
nonsense	4					4
start loss			2			2
frameshift	5		1			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	4	2			8
splice region			8	12		20
non coding			1	30	10	41
Total	11	5	107	83	16

Highest pathogenic variant AF is 0.0000328

Variants in REEP6

This is a list of pathogenic ClinVar variants found in the REEP6 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-1491256-GGCGCGTCGGGGCCATGGACGGCCTGAGGCA-G			Uncertain significance (Jun 24, 2022)
19-1491270-A-G			Uncertain significance (Jul 14, 2023)
19-1491275-C-T			Likely benign (May 06, 2020)
19-1491276-G-A			Uncertain significance (Oct 25, 2022)
19-1491288-C-A			Uncertain significance (Jul 25, 2022)
19-1491294-G-A		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
19-1491296-G-C		Inborn genetic diseases	Uncertain significance (May 13, 2024)
19-1491299-C-T		REEP6-related disorder	Likely benign (Feb 28, 2019)
19-1491314-G-A			Likely benign (Mar 22, 2021)
19-1491316-A-G			Uncertain significance (Aug 28, 2021)
19-1491319-T-C			Uncertain significance (Jun 07, 2020)
19-1491331-T-C			Uncertain significance (Jul 14, 2023)
19-1491338-G-T			Likely benign (Jun 13, 2022)
19-1491340-C-T			Uncertain significance (Mar 19, 2022)
19-1491346-A-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2024)
19-1491348-G-A			Uncertain significance (Jul 14, 2023)
19-1491357-G-C			Uncertain significance (Dec 05, 2019)
19-1491360-G-A			Uncertain significance (Sep 07, 2022)
19-1491362-G-T			Likely benign (Jul 11, 2022)
19-1491364-A-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
19-1491364-A-T			Uncertain significance (Oct 24, 2022)
19-1491365-G-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 17, 2024)
19-1491370-G-C			Uncertain significance (Aug 01, 2022)
19-1491372-T-C			Uncertain significance (Jul 02, 2022)
19-1491374-T-C			Likely benign (May 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REEP6	protein_coding	protein_coding	ENST00000233596	5	6762

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000169	0.451	125391	0	17	125408	0.0000678

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.157	115	110	1.04	0.00000755	1155
Missense in Polyphen		39	37.667	1.0354		361
Synonymous	0.357	53	56.4	0.939	0.00000469	377
Loss of Function	0.470	8	9.57	0.836	5.09e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000243
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000621	0.0000618
Middle Eastern	0.000272	0.000272
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in intracellular protein transport from the endoplasmic reticulum to the cell surface (By similarity). Required for correct function and survival of retinal photoreceptors (PubMed:27889058). {ECO:0000250|UniProtKB:Q9JM62, ECO:0000269|PubMed:27889058}.
• Pathway: Signaling by GPCR;Signal Transduction;Olfactory Signaling Pathway;G alpha (s) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.0385

Intolerance Scores

• loftool: 0.462
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.0646
• hipred: N
• hipred_score: 0.197
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.763

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Reep6
• Phenotype: vision/eye phenotype; 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); cellular phenotype

Zebrafish Information Network

• Gene name: reep6
• Affected structure: retina layer formation
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: regulation of intracellular transport;detection of light stimulus involved in visual perception
• Cellular component: photoreceptor inner segment;nucleus;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;rod spherule;apical part of cell
• Molecular function: protein binding