ZC3H12D

protein-coding

zinc finger CCCH-type containing 12D, the group of Zinc fingers CCCH-type

Gene summary

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]

Previous symbols:

C6orf95

MANE transcript

NM_207360.3

Inheritance

—

ClinVar variants

U:82B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr6:149,446,795-149,485,014

External References & Databases

Ensembl (ENSG00000178199)

Transcript & Mutation Effects

hg38 • Region Span ~38.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZC3H12D variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207360.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			81 clinvar	7 clinvar	1 clinvar	89
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	82	9	1	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207360.3	RefSeq	NP_997243.2	5	MANE Select
ENST00000409806.8	Ensembl	ENSP00000386616.3	5	MANE Select
ENST00000409948.1	Ensembl	ENSP00000387062.1	3	Standard
ENST00000458251.1	Ensembl	ENSP00000395209.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

3'-UTR-mediated mRNA destabilization
nucleic acid phosphodiester bond hydrolysis

Molecular Function

endonuclease activity
protein binding
metal ion binding

Cellular Component

P-body
nucleoplasm
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409806
Coding exons: 5
Length: 37404
Individuals with no LoFs: 124633
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124642
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.40	203	268	0.759	0.0000167	3316
Missense (PolyPhen)		57	101.44	0.56193		1115
Synonymous	2.75	83	122	0.683	0.00000824	1144
Loss of Function	2.11	3	10.3	0.291	5.10e-7	118

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000067	0.000065	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May regulate cell growth likely by suppressing RB1 phosphorylation (PubMed:19531561). May function as RNase and regulate the levels of target RNA species (Potential). In association with ZC3H12A enhances the degradation of interleukin IL-6 mRNA level in activated macrophages (PubMed:26134560). Serve as a tumor suppressor in certain leukemia cells (PubMed:17210687). Overexpression inhibits the G1 to S phase progression through suppression of RB1 phosphorylation (PubMed:19531561). {ECO:0000269|PubMed:17210687, ECO:0000269|PubMed:19531561, ECO:0000269|PubMed:26134560, ECO:0000305}.;
Disease: DISEASE: Note=A chromosomal aberration involving ZC3H12D may be the cause of the transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL). Translocation t(2;6)(p12;q25) with IGK. Resulting protein may not be expressed.;

Recessive Scores

pRec: 0.107

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.384

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium