LY6E

Chr 8

lymphocyte antigen 6 family member E

Also known as: RIG-E, RIGE, SCA-2, SCA2, TSA-1

NCBI Gene: 4061 ENSG00000160932 UniProt: Q16553 OMIM: 601384

The LY6E protein is a GPI-anchored cell surface protein that regulates T-cell proliferation, differentiation and activation through modulation of T-cell receptor signaling, and also restricts coronavirus entry by interfering with spike protein-mediated membrane fusion. Mutations in LY6E cause autosomal recessive severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation. The gene shows moderate tolerance to loss-of-function variation (LOEUF 1.116), and the condition typically presents in early infancy with recurrent infections and developmental delays.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the human Ly6 gene family and encodes a glycosylphosphatidyl-inositol (GPI)-anchored cell surface protein. The protein plays an important role in T cell physiology, oncogenesis and immunological regulation. The protein is also involved in modulation of viral infection by coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2. [provided by RefSeq, Aug 2021]

OMIM ResearchGenerating clinical summary…

LOEUF 1.12

Clinical Summary— LY6E

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

19 VUS of 38 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.321

Z-score 1.45

OE 0.24 (0.08–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.57Z-score

OE missense 0.82 (0.67–1.01)

67 obs / 81.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.08–1.12)

0≤0.351.4

Missense OE?0.82 (0.67–1.01)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 1 / 4.2Missense obs/exp: 67 / 81.6Syn Z: -0.16

ClinVar Variant Classifications

38 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

Likely Benign2

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	19	0	19
Likely Benign	2	0	2
Benign	1	2	3
Total	22	2	24

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap LY6E — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →