GCSAM

Chr 3

germinal center associated signaling and motility

Also known as: GCAT2, GCET2, HGAL

The protein regulates lymphocyte motility through negative regulation and mediates migration-inhibitory effects of IL6, while also serving as a positive regulator of RhoA signaling and B-cell receptor signaling through SYK kinase activation. Based on the available data, no well-established human disease associations have been documented for mutations in this gene. The gene shows low constraint against loss-of-function variants (pLI 0.06, LOEUF 1.0), suggesting tolerance to such mutations in the general population.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.00
Clinical SummaryGCSAM
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.064
Z-score 1.59
OE 0.39 (0.171.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.49Z-score
OE missense 0.86 (0.721.03)
83 obs / 96.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.171.00)
00.351.4
Missense OE0.86 (0.721.03)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 3 / 7.8Missense obs/exp: 83 / 96.6Syn Z: -0.28
DN
0.76top 25%
GOF
0.80top 10%
LOF
0.1797th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GCSAM · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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