SLAMF8

Chr 1

SLAM family member 8

Also known as: BLAME, CD353, SBBI42

This gene encodes a member of the CD2 family of cell surface proteins involved in lymphocyte activation. These proteins are characterized by Ig domains. This protein is expressed in lymphoid tissues, and studies of a similar protein in mouse suggest that it may function during B cell lineage commitment. The gene is found in a region of chromosome 1 containing many CD2 genes. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.19
Clinical SummarySLAMF8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.19LOEUF
pLI 0.000
Z-score 1.04
OE 0.70 (0.431.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.29Z-score
OE missense 1.06 (0.941.21)
172 obs / 161.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.70 (0.431.19)
00.351.4
Missense OE?1.06 (0.941.21)
00.61.4
Synonymous OE?0.95
01.21.6
LoF obs/exp: 10 / 14.2Missense obs/exp: 172 / 161.7Syn Z: 0.31

This gene — mechanism propensity

DN
0.7035th %ile
GOF
0.6540th %ile
LOF
0.2777th %ile

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

DNprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLAMF8 · protein map & ClinVar variants

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