NFATC2IP

Chr 16

nuclear factor of activated T cells 2 interacting protein

Also known as: ESC2, NIP45, RAD60

NCBI Gene: 84901 ENSG00000176953 UniProt: Q8NCF5 OMIM: 614525

This protein regulates NFAT-driven transcription of specific cytokine genes including IL4, IL5, and IL13 in T-helper 2 cells by recruiting PRMT1 to promote histone methylation and acetylation. Mutations cause autosomal recessive primary immunodeficiency with defective T-helper cell cytokine production, resulting in recurrent infections and immune dysregulation typically presenting in early childhood. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.02

Clinical Summary— NFATC2IP

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

52 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.51

OE 0.60 (0.37–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.64Z-score

OE missense 0.88 (0.78–0.99)

190 obs / 216.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.37–1.02)

0≤0.351.4

Missense OE?0.88 (0.78–0.99)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 10 / 16.7Missense obs/exp: 190 / 216.5Syn Z: 1.42

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS52

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	52	52
Likely Benign	2	2
Benign	0	0
Total	54	54

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap NFATC2IP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →