ZNF396

protein-coding

zinc finger protein 396, the group of Zinc fingers C2H2-type|SCAN domain containing

Gene summary

Enables protein heterodimerization activity; protein homodimerization activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of DNA-templated transcription. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001322286.2

Inheritance

—

ClinVar variants

U:38B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr18:35,366,694-35,377,337

External References & Databases

Ensembl (ENSG00000186496)

Transcript & Mutation Effects

hg38 • Region Span ~10.6 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 ZNF396 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 39

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001322286.2. 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						0
missense			38 clinvar	2 clinvar		40
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	0	0	38	2	1	41

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001322286.2	RefSeq	NP_001309215.1	3	MANE Select
ENST00000589332.7	Ensembl	ENSP00000466500.1	3	MANE Select
NM_001322290.2	RefSeq	NP_001309219.1	3	Standard
NM_001322291.2	RefSeq	NP_001309220.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
metal ion binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306346
Coding exons: 4
Length: 10641
Individuals with no LoFs: 125345
Homozygous LoFs: 6
Heterozygous LoFs: 397
Defined: 125748
p: 0.00160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.491	154	172	0.895	0.00000832	2183
Missense (PolyPhen)		23	28.966	0.79403		357
Synonymous	1.30	52	65.3	0.796	0.00000326	618
Loss of Function	1.23	10	15.2	0.659	7.46e-7	180

Population LoF Frequency

Population	CAF	p-value	Status
African	0.017	0.017	notable
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0026	0.0026	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00092	0.00088	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1 and isoform 2 act as DNA-dependent transcriptional repressors. {ECO:0000269|PubMed:12801647}.;

Intolerance Scores

LoFtool: 0.716
RVIS EVS: -0.05
RVIS percentile EVS: 50.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.920

Gene Damage Prediction

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