NFATC2

Chr 20AR

nuclear factor of activated T cells 2

Also known as: JCOSL, NFAT1, NFATP

NCBI Gene: 4773ENSG00000101096UniProt: Q13469

The NFATC2 protein is a transcription factor that translocates to the nucleus upon T cell receptor stimulation to induce cytokine gene expression and plays a role in regulating chondrogenesis. Biallelic mutations cause joint contracture, osteochondromas, and B-cell lymphoma with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.19), indicating that such variants are likely pathogenic.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Joint contracture, osteochondromas, and B-cell lymphomaMIM #620232
AR
UniProtJoint contractures, osteochondromas, and B-cell lymphoma
0
Active trials
56
Pubs (1 yr)
12
P/LP submissions
8%
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— NFATC2
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 129 VUS of 171 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 5.53
OE 0.07 (0.03–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.64Z-score
OE missense 0.81 (0.75–0.87)
485 obs / 597.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.03–0.19)
0≤0.351.4
Missense OE0.81 (0.75–0.87)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 3 / 41.4Missense obs/exp: 485 / 597.9Syn Z: -0.45
DN
0.3494th %ile
GOF
0.2198th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS129
Likely Benign9
Benign6
9
Pathogenic
3
Likely Pathogenic
129
VUS
9
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
8
0
9
Likely Pathogenic
0
1
2
0
3
VUS
0
126
3
0
129
Likely Benign
0
4
0
5
9
Benign
0
2
1
3
6
Total1133148156

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

View in ClinVar →

Protein Context — Lollipop Plot

NFATC2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients