ZCCHC4

protein-coding

zinc finger CCHC-type containing 4, the group of Zinc fingers CCHC-type|Zinc fingers GRF-type|7BS N6-adenosine DNA/RNA methyltransferases

Gene summary

Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_024936.3

Inheritance

—

ClinVar variants

U:89B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr4:25,312,774-25,370,383

External References & Databases

Ensembl (ENSG00000168228)

Transcript & Mutation Effects

hg38 • Region Span ~57.6 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 ZCCHC4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 83

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024936.3. 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	4 clinvar		6
missense			84 clinvar	1 clinvar	4 clinvar	89
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	89	5	4	98

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024936.3	RefSeq	NP_079212.2	13	MANE Select
ENST00000302874.9	Ensembl	ENSP00000303468.4	13	MANE Select
NM_001318148.2	RefSeq	NP_001305077.1	9	Standard
ENST00000505412.1	Ensembl	ENSP00000422269.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

methylation

Molecular Function

nucleic acid binding
methyltransferase activity
zinc ion binding
transferase activity, transferring acyl groups

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302874
Coding exons: 13
Length: 57599
Individuals with no LoFs: 124443
Homozygous LoFs: 0
Heterozygous LoFs: 355
Defined: 124798
p: 0.00142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0104	274	274	0.998	0.0000138	3393
Missense (PolyPhen)		48	56.265	0.85311		670
Synonymous	0.934	87	98.8	0.880	0.00000515	907
Loss of Function	1.78	20	30.6	0.653	0.00000170	363

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00026	rare
Latino/Admixed American	0.0020	0.0019	notable
Ashkenazi Jewish	0.0011	0.0011	notable
East Asian	0.0011	0.0011	notable
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0019	0.0019	notable
South Asian	0.00068	0.00062	rare
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be a methyltransferase.;

Recessive Scores

pRec: 0.0910

Intolerance Scores

LoFtool: 0.868
RVIS EVS: 1.8
RVIS percentile EVS: 96.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.905

Gene Damage Prediction

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