LGALS9C

Chr 17

galectin 9C

Also known as: gal-9C

NCBI Gene: 654346 ENSG00000171916 UniProt: Q6DKI2

The protein binds galactosides and is structurally highly similar to galectin 9. This gene is not well-constrained against loss-of-function variants and currently lacks established disease associations in pediatric patients.

ResearchSummary from RefSeq, UniProt

This gene was initially thought to represent a pseudogene of galectin 9; however, this transcript has good exon-intron structure and encodes a predicted protein of the same size as and highly similar to galectin 9. This gene is one of two similar loci on chromosome 17p similar to galectin 9 and now thought to be protein-encoding. This gene is the more telomeric gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.51

Clinical Summary— LGALS9C

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Population Constraint (gnomAD)

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

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ClinVar Variants

53 VUS of 65 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.000

Z-score 0.17

OE 0.95 (0.62–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.90Z-score

OE missense 0.82 (0.72–0.93)

155 obs / 189.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.95 (0.62–1.51)

0≤0.351.4

Missense OE?0.82 (0.72–0.93)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 13 / 13.7Missense obs/exp: 155 / 189.8Syn Z: 0.92

This gene — mechanism propensity

0.7327th %ile

GOF

0.4777th %ile

LOF

0.3454th %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

65 submitted variants in ClinVar

ClinVar

Classification Summary

VUS53

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	53	53
Likely Benign	1	5	6
Benign	0	0	0
Total	1	58	59

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

View in ClinVar →

105 pathogenic / likely-pathogenic (of 109) ClinVar copy-number / structural variants overlap LGALS9C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →