ZNF366

protein-coding

zinc finger protein 366, the group of Zinc fingers C2H2-type

Gene summary

Enables nuclear estrogen receptor binding activity and transcription corepressor activity. Involved in negative regulation of intracellular estrogen receptor signaling pathway; negative regulation of transcription by RNA polymerase II; and response to estrogen. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_152625.3

Inheritance

—

ClinVar variants

U:138B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr5:72,439,903-72,507,410

External References & Databases

Ensembl (ENSG00000178175)

Transcript & Mutation Effects

hg38 • Region Span ~67.5 kb

Loading mutation effect viewer...

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 ZNF366 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 134

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152625.3. 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			135 clinvar	4 clinvar		139
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	138	4	0	142

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152625.3	RefSeq	NP_689838.1	4	MANE Select
ENST00000318442.6	Ensembl	ENSP00000313158.5	4	MANE Select
ENST00000414109.2	Ensembl	ENSP00000391333.2	1	Standard
ENST00000867840.1	Ensembl	ENSP00000537899.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
negative regulation of intracellular estrogen receptor signaling pathway
response to estrogen

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
transcription corepressor activity
protein binding
estrogen receptor binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318442
Coding exons: 4
Length: 65076
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0630	466	462	1.01	0.0000305	4950
Missense (PolyPhen)		135	172.13	0.78431		1800
Synonymous	-0.404	209	202	1.04	0.0000152	1402
Loss of Function	3.40	7	25.5	0.274	0.00000128	311

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000099	0.000098	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has transcriptional repression activity. Acts as corepressor of ESR1; the function seems to involve CTBP1 and histone deacetylases. {ECO:0000269|PubMed:17085477}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

RVIS EVS: 0.25
RVIS percentile EVS: 69.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.266

Gene Damage Prediction

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