LY6G5B

Chr 6

lymphocyte antigen 6 family member G5B

Also known as: C6orf19, G5b

NCBI Gene: 58496 ENSG00000240053 UniProt: Q8NDX9 OMIM: 610433

The LY6G5B protein is a cell surface glycoprotein anchored by glycosylphosphatidylinositol (GPI) that participates in signal transduction and belongs to the leukocyte antigen-6 superfamily within the MHC class III region. This gene is extremely intolerant to loss-of-function mutations (pLI near 1.0), but no established human disease associations have been reported for LY6G5B mutations.

OMIM ResearchSummary from RefSeq

LY6G5B belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.64

Clinical Summary— LY6G5B

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 28 VUS of 39 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?

1.64LOEUF

pLI 0.000

Z-score 0.17

OE 0.94 (0.55–1.64)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.10Z-score

OE missense 1.03 (0.88–1.19)

120 obs / 117.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.94 (0.55–1.64)

0≤0.351.4

Missense OE?1.03 (0.88–1.19)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 8 / 8.5Missense obs/exp: 120 / 117.0Syn Z: 0.88

This gene — mechanism propensity

0.6163th %ile

GOF

0.73top 25%

LOF

0.3067th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS28

Likely Benign5

Benign2

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	28	0	0	28
Likely Benign	5	0	0	5
Benign	0	1	1	2
Total	34	1	1	36

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap LY6G5B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →