KLRD1

Chr 12

killer cell lectin like receptor D1

Also known as: CD94

KLRD1 encodes CD94, an immune receptor that forms complexes with other proteins on natural killer cells and cytotoxic T lymphocytes to recognize HLA-E molecules and enable self-nonself discrimination. The gene shows low constraint to loss-of-function mutations (pLI 0.0009, LOEUF 1.21), and no Mendelian diseases have been definitively associated with KLRD1 mutations in current databases. While the protein is critical for normal immune surveillance, pathogenic variants causing pediatric neurologic disease have not been established.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
23
Pubs (1 yr)
38
P/LP submissions
0%
P/LP missense
1.21
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryKLRD1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 17 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.21LOEUF
pLI 0.001
Z-score 1.11
OE 0.62 (0.341.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.43Z-score
OE missense 0.87 (0.731.05)
81 obs / 92.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.341.21)
00.351.4
Missense OE0.87 (0.731.05)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 6 / 9.8Missense obs/exp: 81 / 92.6Syn Z: 0.97
DN
0.7327th %ile
GOF
0.73top 25%
LOF
0.2190th %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

67 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic2
VUS17
Likely Benign4
36
Pathogenic
2
Likely Pathogenic
17
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
2
0
2
VUS
0
15
2
0
17
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total01841059

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

View in ClinVar →

Protein Context — Lollipop Plot

KLRD1 · 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.

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Clinical Literature
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