CD244

Chr 1

CD244 molecule

Also known as: 2B4, NAIL, NKR2B4, Nmrk, SLAMF4

This gene encodes a cell surface receptor expressed on natural killer (NK) cells (and some T cells) that mediate non-major histocompatibility complex (MHC) restricted killing. The interaction between NK-cell and target cells via this receptor is thought to modulate NK-cell cytolytic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.581 OMIM phenotype
Clinical SummaryCD244
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
38 VUS of 58 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.58LOEUF
pLI 0.057
Z-score 2.97
OE 0.29 (0.160.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.30Z-score
OE missense 0.94 (0.831.06)
179 obs / 190.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.29 (0.160.58)
00.351.4
Missense OE?0.94 (0.831.06)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 6 / 20.5Missense obs/exp: 179 / 190.7Syn Z: -0.43

This gene — mechanism propensity

DN
0.84top 10%
GOF
0.7126th %ile
LOF
0.1796th %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

58 submitted variants in ClinVar

Classification Summary

VUS38
Likely Benign10
Benign4
38
VUS
10
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
38
0
0
38
Likely Benign
0
10
0
0
10
Benign
0
2
1
1
4
Total0501152

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap CD244 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CD244 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →