LY6G5C

Chr 6

lymphocyte antigen 6 family member G5C

Also known as: C6orf20, G5C, LY6G5CA, LY6G5CB, NG33

NCBI Gene: 80741 ENSG00000204428 UniProt: Q5SRR4 OMIM: 610434

The LY6G5C protein is a GPI-anchored cell surface protein that may function in hematopoietic cell differentiation and belongs to the leukocyte antigen-6 superfamily involved in signal transduction. No disease associations or inheritance patterns have been established for mutations in this gene based on the available information.

OMIM ResearchSummary from RefSeq, UniProt

LY6G5C 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…

DNmechanismLOEUF 0.93

Clinical Summary— LY6G5C

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.

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ClinVar Variants

9 VUS of 15 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?

0.93LOEUF

pLI 0.405

Z-score 1.68

OE 0.20 (0.07–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.34Z-score

OE missense 0.59 (0.47–0.75)

49 obs / 83.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.07–0.93)

0≤0.351.4

Missense OE?0.59 (0.47–0.75)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 1 / 5.1Missense obs/exp: 49 / 83.4Syn Z: 0.37

This gene — mechanism propensity

0.6841th %ile

GOF

0.5759th %ile

LOF

0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

15 submitted variants in ClinVar

ClinVar

Classification Summary

VUS9

Likely Benign2

VUS

Likely 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	9	0	9
Likely Benign	1	1	2
Benign	0	0	0
Total	10	1	11

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 LY6G5C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →