EYS

Chr 6AR

EGF-like photoreceptor maintenance factor

Also known as: C6orf178, C6orf179, C6orf180, EGFL10, EGFL11, RP25, SPAM, bA166P24.2

NCBI Gene: 346007ENSG00000188107UniProt: Q5T1H1

The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

Retinitis pigmentosa 25MIM #602772
AR
589
ClinVar variants
66
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— EYS
🧬
Gene-Disease Validity (ClinGen)
EYS-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 247 VUS of 589 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 3.09
OE 0.69 (0.58–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.32Z-score
OE missense 0.98 (0.93–1.02)
1441 obs / 1475.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.58–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.93–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 83 / 119.4Missense obs/exp: 1441 / 1475.3Syn Z: 0.63

ClinVar Variant Classifications

589 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic26
VUS247
Likely Benign265
Benign11
40
Pathogenic
26
Likely Pathogenic
247
VUS
265
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
1
21
0
40
Likely Pathogenic
15
2
9
0
26
VUS
5
202
22
18
247
Likely Benign
0
5
121
139
265
Benign
0
2
9
0
11
Total38212182157589

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EYS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

EYS-related retinitis pigmentosa

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Retinitis pigmentosa 25

MIM #602772

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EYS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients.
Koyanagi Y et al.·J Med Genet
2019Cohort
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.
Jespersgaard C et al.·Sci Rep
2019
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.
Sun T et al.·Invest Ophthalmol Vis Sci
2018Cohort
Impact of Next Generation Sequencing in Unraveling the Genetics of 1036 Spanish Families With Inherited Macular Dystrophies.
Del Pozo-Valero M et al.·Invest Ophthalmol Vis Sci
2022
Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations.
Zampaglione E et al.·Genet Med
2020
A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).
Sharon D et al.·Hum Mutat
2020
Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing.
Suga A et al.·Hum Mutat
2022
Whole-exome sequencing in 168 Korean patients with inherited retinal degeneration.
Ma DJ et al.·BMC Med Genomics
2021Cohort
Diverse Genetic Landscape of Suspected Retinitis Pigmentosa in a Large Korean Cohort.
Kim YJ et al.·Genes (Basel)
2021Cohort
Application of targeted panel sequencing and whole exome sequencing for 76 Chinese families with retinitis pigmentosa.
Dan H et al.·Mol Genet Genomic Med
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Retinitis PigmentosaEye Diseases

Natural History Study of Patients With EYS-Associated RP

RECRUITING
NCT07228793Sensor Technology for DeafblindStarted 2025-11-07
Whole exome/genome sequencing

External Resources

Links to major genomics databases and tools