ZC3H12D

Chr 6

zinc finger CCCH-type containing 12D

Also known as: C6orf95, MCPIP4, TFL, dJ281H8.1, p34

NCBI Gene: 340152ENSG00000178199UniProt: A2A288

Predicted to enable RNA endonuclease activity and mRNA binding activity. Involved in negative regulation of G1/S transition of mitotic cell cycle and negative regulation of cell growth. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

112
ClinVar variants
21
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— ZC3H12D
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 81 VUS of 112 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.156
Z-score 2.11
OE 0.29 (0.13–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.40Z-score
OE missense 0.76 (0.68–0.85)
203 obs / 267.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.13–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.68–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.68
0≤1.21.6
LoF obs/exp: 3 / 10.3Missense obs/exp: 203 / 267.6Syn Z: 2.75

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS81
Likely Benign9
Benign1
20
Pathogenic
1
Likely Pathogenic
81
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
0
78
3
0
81
Likely Benign
0
7
0
2
9
Benign
0
1
0
0
1
Total086242112

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

View in ClinVar →

Protein Context — Lollipop Plot

ZC3H12D · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ZC3H12D gene expression exhibits dual effects on the development and progression of lung adenocarcinoma.
Zheng Y et al.·Sci Rep
2025
ZC3H12D upregulation in head and neck squamous cell carcinoma: a potential prognostic biomarker associated with immune infiltration.
Zhao M et al.·Braz J Med Biol Res
2025
A molecular network regulating the proinflammatory phenotype of human memory T lymphocytes.
Emming S et al.·Nat Immunol
2020
Transformed Follicular Lymphoma (TFL) Predicts Outcome in Advanced Endometrial Cancer.
Wakahashi S et al.·Cancer Epidemiol Biomarkers Prev
2018
Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma.
Huang Z et al.·Bioengineered
2021
Comprehensive analysis of the functions, prognostic and diagnostic values of RNA binding proteins in head and neck squamous cell carcinoma.
Liu H et al.·J Stomatol Oral Maxillofac Surg
2024
Mining, validating, and quantifying circular RNA transcriptome from total RNA as a biomarker or target.
Wang TZ et al.·Sci Rep
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools