ZC3H12A

Chr 1

zinc finger CCCH-type containing 12A

Also known as: MCPIP, MCPIP-1, MCPIP1, Reg1, dJ423B22.1

ZC3H12A encodes an endoribonuclease that degrades inflammation-related mRNAs and regulates immune homeostasis, while also promoting glial differentiation of neuroprogenitor cells. Mutations cause autosomal recessive combined immunodeficiency with susceptibility to viral infections and warts. The gene is highly constrained against loss-of-function variants (LOEUF 0.51), indicating that complete loss of function is poorly tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.51
Clinical SummaryZC3H12A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.140
Z-score 3.30
OE 0.26 (0.140.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.18Z-score
OE missense 0.68 (0.610.76)
253 obs / 371.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.26 (0.140.51)
00.351.4
Missense OE0.68 (0.610.76)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 6 / 23.2Missense obs/exp: 253 / 371.5Syn Z: -0.45

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZC3H12A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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