NFATC1

Chr 18

nuclear factor of activated T cells 1

Also known as: NF-ATC, NF-ATc1.2, NFAT2, NFATc

NFATC1 encodes a transcription factor that regulates cytokine gene expression in T cells and controls gene expression in embryonic cardiac development, osteoclast differentiation, and lymphocyte function. Mutations cause congenital heart defects and immunodeficiency with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.447), indicating that such mutations are likely to be pathogenic.

Summary from RefSeq, UniProt
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1
Active trials
274
Pubs (1 yr)
77
P/LP submissions
0%
P/LP missense
0.45
LOEUF
Mechanism
Clinical SummaryNFATC1
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADDisputed

Disputed — evidence questions this relationship

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
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ClinVar Variants
77 unique Pathogenic / Likely Pathogenic· 244 VUS of 499 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — NFATC1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.157
Z-score 3.96
OE 0.25 (0.140.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.74Z-score
OE missense 0.92 (0.860.98)
590 obs / 642.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.140.45)
00.351.4
Missense OE0.92 (0.860.98)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 8 / 32.3Missense obs/exp: 590 / 642.4Syn Z: -1.45

ClinVar Variant Classifications

499 submitted variants in ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic6
VUS244
Likely Benign119
Benign38
Conflicting6
71
Pathogenic
6
Likely Pathogenic
244
VUS
119
Likely Benign
38
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
71
0
71
Likely Pathogenic
0
0
6
0
6
VUS
1
215
27
1
244
Likely Benign
0
23
24
72
119
Benign
1
7
4
26
38
Conflicting
6
Total224513299484

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

View in ClinVar →

Protein Context — Lollipop Plot

NFATC1 · protein map & ClinVar variants

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

Clinical Literature
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