ZC3H12C

Chr 11

zinc finger CCCH-type containing 12C

Also known as: MCPIP3

NCBI Gene: 85463 ENSG00000149289 UniProt: Q9C0D7 OMIM: 615001

The protein functions as an RNA endonuclease that regulates target RNA levels through mRNA binding and cleavage activity in cytoplasmic ribonucleoprotein granules and the nucleus. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable RNA endonuclease activity and mRNA binding activity. Predicted to be involved in 3'-UTR-mediated mRNA destabilization. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.998

Z-score 4.97

OE 0.11 (0.05–0.25)

Highly constrained

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

Missense Constraint?

1.80Z-score

OE missense 0.77 (0.71–0.84)

377 obs / 489.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.25)

0≤0.351.4

Missense OE?0.77 (0.71–0.84)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 4 / 36.4Missense obs/exp: 377 / 489.1Syn Z: 1.69

Background carrier burden — how many people carry a rare variant somewhere in ZC3H12C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 72

944 rare PASS variants

Rare truncating (LoF)

1 in 1,200

78 rare PASS variants

Rare synonymous (reference)

1 in 160

375 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZC3H12C. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 83	1 in 1,200
South Asian	~43k	1 in 61	1 in 580
Remaining (unassigned)	~30k	1 in 55	1 in 960
European (Finnish)	~27k	1 in 180	≈ 1 in 7,500
Admixed American	~22k	1 in 56	1 in 910
African / African American	~21k	1 in 80	1 in 1,200
East Asian	~20k	1 in 100	1 in 1,600
Ashkenazi Jewish	~13k	1 in 490	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 69	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 5 of 6 (exon 1 below).? see exons ↓