ZNF589

protein-coding

zinc finger protein 589, the group of Zinc fingers C2H2-type

Gene summary

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_016089.3

Inheritance

ClinVar variants

U:47B:4

Top phenotype

ZNF589-related disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr3:48,241,100-48,299,253

External References & Databases

Ensembl (ENSG00000164048)

Transcript & Mutation Effects

hg38 • Region Span ~58.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF589 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 47

ZNF589-related disorderTotal: 4

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016089.3. 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				1 clinvar		1
missense			47 clinvar	1 clinvar	1 clinvar	49
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	47	3	1	51

Loading ClinVar variants...

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_016089.3	RefSeq	NP_057173.2	4	MANE Select
ENST00000354698.8	Ensembl	ENSP00000346729.3	4	MANE Select
ENST00000412564.5	Ensembl	ENSP00000404398.1	4	Standard
ENST00000412564.6	Ensembl	ENSP00000404398.1	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

negative regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
metal ion binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354698
Coding exons: 4
Length: 58154
Individuals with no LoFs: 125206
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125212
p: 0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0571	191	193	0.988	0.00000952	2366
Missense (PolyPhen)		45	37.907	1.1871		488
Synonymous	0.760	66	74.3	0.888	0.00000380	707
Loss of Function	0.723	4	5.90	0.678	2.52e-7	61

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in hematopoietic stem/progenitor cell differentiation. May play a role as a DNA binding-dependent transcriptional repressor. {ECO:0000269|PubMed:10029171, ECO:0000269|PubMed:12097288}.;

Recessive Scores

pRec: 0.0820

Intolerance Scores

LoFtool: 0.768
RVIS EVS: -0.12
RVIS percentile EVS: 45.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.175

Gene Damage Prediction

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