ZNF454

protein-coding

zinc finger protein 454, the group of Zinc fingers C2H2-type

Gene summary

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001178089.3

Inheritance

—

ClinVar variants

U:52B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr5:178,941,191-178,966,433

External References & Databases

Ensembl (ENSG00000178187)

Transcript & Mutation Effects

hg38 • Region Span ~25.2 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 ZNF454 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 52

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001178089.3. 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						0
missense			51 clinvar	1 clinvar		52
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	52	1	0	53

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001178089.3	RefSeq	NP_001171560.1	4	MANE Select
ENST00000519564.2	Ensembl	ENSP00000430354.1	4	MANE Select
NM_001178090.3	RefSeq	NP_001171561.1	4	Standard
NM_001323306.2	RefSeq	NP_001310235.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320129
Coding exons: 4
Length: 25243
Individuals with no LoFs: 125681
Homozygous LoFs: 0
Heterozygous LoFs: 67
Defined: 125748
p: 0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.29	216	276	0.782	0.0000131	3510
Missense (PolyPhen)		72	108.84	0.66152		1383
Synonymous	0.0646	97	97.8	0.992	0.00000498	899
Loss of Function	1.84	12	21.1	0.568	0.00000114	272

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00023	0.00023	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;

Intolerance Scores

LoFtool: 0.816
RVIS EVS: 0.33
RVIS percentile EVS: 73.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.171

Gene Damage Prediction

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