EYS

eyes shut homolog

Basic information

Region (hg38): 6:63719979-65707226

Previous symbols: [ "C6orf180", "EGFL11", "RP25", "EGFL10", "C6orf178", "C6orf179" ]

Links

ENSG00000188107 ∙ NCBI:346007 ∙ OMIM:612424 ∙ HGNC:21555 ∙ Uniprot:Q5T1H1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 25 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 25 (Definitive), mode of inheritance: AR
• EYS-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retitinis pigmentosa 25	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	18836446; 18976725; 21069908; 21179430; 21519034; 22277662; 22302105; 22363543

ClinVar

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

• not provided (3443 variants)
• Retinitis pigmentosa 25 (838 variants)
• Retinitis pigmentosa (369 variants)
• Autosomal recessive retinitis pigmentosa (134 variants)
• Inborn genetic diseases (116 variants)
• Retinal dystrophy (115 variants)
• not specified (98 variants)
• Retinitis Pigmentosa, Recessive (12 variants)
• EYS-related condition (7 variants)
• Macular dystrophy (3 variants)
• Central areolar choroidal dystrophy (1 variants)
• 7 conditions (1 variants)
• Abnormality of the eye (1 variants)
• See cases (1 variants)
• Visual impairment;Blurred vision;Rod-cone dystrophy;Retinal detachment;Central scotoma (1 variants)
• Stargardt disease (1 variants)
• Color vision defect;Retinal dystrophy;Visual impairment;Horizontal nystagmus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EYS 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	8	1013	13	1035
missense	6	12	1170	32	24	1244
nonsense	143	98				241
start loss						0
frameshift	204	146	3			353
inframe indel	1		18			19
splice donor/acceptor (+/-2bp)	15	93	2	1		111
splice region		2	39	131	14	186
non coding			84	216	107	407
Total	369	350	1285	1262	144

Highest pathogenic variant AF is 0.000637

Variants in EYS

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

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

Position	Type	Phenotype	Significance	ClinVar
6-63720042-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-63720048-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-63720067-T-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-63720082-T-C		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
6-63720183-AT-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-63720310-A-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-63720318-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-63720407-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
6-63720498-T-C		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-63720597-T-C			Likely benign (Jun 12, 2023)
6-63720598-A-C			Uncertain significance (Aug 10, 2022)
6-63720598-AT-A			Uncertain significance (Oct 13, 2022)
6-63720599-T-C		Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
6-63720601-T-TAA		Retinitis pigmentosa 25 • not specified	Conflicting classifications of pathogenicity (Apr 12, 2023)
6-63720604-C-T			Uncertain significance (Mar 11, 2022)
6-63720608-A-G			Likely benign (Mar 01, 2019)
6-63720611-T-G		Retinitis pigmentosa 25	Uncertain significance (Sep 13, 2022)
6-63720614-T-C			Likely benign (Dec 31, 2022)
6-63720615-TCATCTC-T			Uncertain significance (Jan 19, 2024)
6-63720617-A-C		Retinitis pigmentosa 25 • Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
6-63720623-A-G			Likely benign (Jun 27, 2023)
6-63720626-A-G			Likely benign (Jul 21, 2023)
6-63720626-A-T		Retinitis pigmentosa 25 • Retinal dystrophy • Retinitis pigmentosa • EYS-related disorder	Pathogenic/Likely pathogenic (Mar 01, 2024)
6-63720628-A-G		Inborn genetic diseases	Uncertain significance (Mar 21, 2023)
6-63720628-A-AAACATTGTATCCTTCTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNAGACGGGGTTTCACCGTTTTAGCCGGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCC			Pathogenic (Mar 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EYS	protein_coding	protein_coding	ENST00000503581	40	1987243

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.72e-41	0.739	125670	0	27	125697	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.318	1441	1.48e+3	0.977	0.0000703	20735
Missense in Polyphen		323	374.4	0.86271		5355
Synonymous	0.633	513	532	0.965	0.0000261	5835
Loss of Function	3.09	83	119	0.695	0.00000569	1798

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000427	0.000426
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000797	0.0000792
Middle Eastern	0.000219	0.000217
South Asian	0.00	0.00
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required to maintain the integrity of photoreceptor cells. {ECO:0000269|PubMed:18836446}.

Recessive Scores

• pRec: 0.0838

Intolerance Scores

• loftool: 0.0537
• rvis_EVS: 7.74
• rvis_percentile_EVS: 99.93

Haploinsufficiency Scores

• pHI: 0.0372
• hipred: N
• hipred_score: 0.146

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Zebrafish Information Network

• Gene name: eys
• Affected structure: retinal rod cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: skeletal muscle tissue regeneration;detection of light stimulus involved in visual perception
• Cellular component: extracellular exosome
• Molecular function: molecular_function;calcium ion binding