ZNF654

protein-coding

zinc finger protein 654, the group of Zinc fingers C2H2-type

Gene summary

Predicted to enable DNA binding activity and DNA-binding transcription factor activity, RNA polymerase II-specific. 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_001350134.2

Inheritance

—

ClinVar variants

U:55B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:88,059,255-88,144,660

External References & Databases

Ensembl (ENSG00000175105)

Transcript & Mutation Effects

hg38 • Region Span ~85.4 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 ZNF654 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001350134.2. 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			1 clinvar			1
missense			50 clinvar	1 clinvar		51
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	55	1	0	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001350134.2	RefSeq	NP_001337063.1	9	MANE Select
ENST00000636215.2	Ensembl	ENSP00000490842.1	9	MANE Select
NM_001350135.2	RefSeq	NP_001337064.1	7	Standard
NM_001350136.2	RefSeq	NP_001337065.1	5	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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309495
Coding exons: 2
Length: 5562
Individuals with no LoFs: 124332
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124335
p: 0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	245	300	0.816	0.0000143	3918
Missense (PolyPhen)		45	101.96	0.44137		1324
Synonymous	0.726	95	104	0.910	0.00000531	1035
Loss of Function	3.89	0	17.6	0.00	8.19e-7	263

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000089	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.151
RVIS EVS: 0.68
RVIS percentile EVS: 85.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.207

Gene Damage Prediction

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