SLAMF6

Chr 1

SLAM family member 6

Also known as: CD352, KALI, KALIb, Ly108, NTB-A, NTBA, SF2000

NCBI Gene: 114836 ENSG00000162739 UniProt: Q96DU3 OMIM: 606446

The protein encoded by this gene is a type I transmembrane protein, belonging to the CD2 subfamily of the immunoglobulin superfamily. This encoded protein is expressed on Natural killer (NK), T, and B lymphocytes. It undergoes tyrosine phosphorylation and associates with the Src homology 2 domain-containing protein (SH2D1A) as well as with SH2 domain-containing phosphatases (SHPs). It functions as a coreceptor in the process of NK cell activation. It can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.68

Clinical Summary— SLAMF6

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

📋

ClinVar Variants

31 VUS of 47 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

0.68LOEUF

pLI 0.019

Z-score 2.54

OE 0.34 (0.19–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.57Z-score

OE missense 0.88 (0.77–1.00)

148 obs / 168.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.19–0.68)

0≤0.351.4

Missense OE?0.88 (0.77–1.00)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 6 / 17.4Missense obs/exp: 148 / 168.9Syn Z: 0.90

This gene — mechanism propensity

0.86top 5%

GOF

0.75top 25%

LOF

0.1498th %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

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	31	31
Likely Benign	6	6
Benign	0	0
Total	37	37

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap SLAMF6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →