CD99

Chr Y

CD99 molecule (Xg blood group)

Also known as: HBA71, MIC2, MIC2X, MIC2Y, MSK5X

CD99 encodes a cell surface glycoprotein that mediates leukocyte migration across endothelial basement membranes and T-cell adhesion processes. Mutations cause 46,XY differences/disorders of sex development with gonadal dysgenesis, inherited in an X-linked pattern. The gene is located in the pseudoautosomal region and escapes X-inactivation, making it tolerant to loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.96
Clinical SummaryCD99
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 2 VUS of 200 total submissions
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GeneReview available — CD99
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.003
Z-score 1.66
OE 0.49 (0.270.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.53Z-score
OE missense 1.14 (0.991.32)
129 obs / 113.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.49 (0.270.96)
00.351.4
Missense OE1.14 (0.991.32)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 6 / 12.3Missense obs/exp: 129 / 113.2Syn Z: -0.16
DN
0.85top 10%
GOF
0.74top 25%
LOF
0.1993th %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

200 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic3
VUS2
Likely Benign2
25
Pathogenic
3
Likely Pathogenic
2
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
Likely Pathogenic
3
VUS
2
Likely Benign
2
Benign
0
Total32

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CD99 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →