ZNF653

protein-coding

zinc finger protein 653, the group of Zinc fingers C2H2-type|MicroRNA protein coding host genes

Gene summary

Enables AF-2 domain binding activity; DNA-binding transcription factor binding activity; and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_138783.4

Inheritance

—

ClinVar variants

U:103B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr19:11,483,427-11,505,839

External References & Databases

Ensembl (ENSG00000161914)

Transcript & Mutation Effects

hg38 • Region Span ~22.4 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 ZNF653 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 107

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138783.4. 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			103 clinvar	7 clinvar		110
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	103	8	0	111

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138783.4	RefSeq	NP_620138.2	9	MANE Select
ENST00000293771.10	Ensembl	ENSP00000293771.3	9	MANE Select
ENST00000588541.5	Ensembl	ENSP00000465674.1	2	Standard
ENST00000589051.1	Ensembl	ENSP00000465955.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
extracellular negative regulation of signal transduction
negative regulation of nucleic acid-templated transcription

Molecular Function

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

Cellular Component

cellular_component
extracellular region
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000293771
Coding exons: 9
Length: 22497
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.67	289	380	0.760	0.0000255	3930
Missense (PolyPhen)		72	129.59	0.55558		1239
Synonymous	-1.56	196	170	1.15	0.0000135	1245
Loss of Function	2.76	9	23.4	0.384	0.00000100	289

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.000057	0.000046	rare
European (Non-Finnish)	0.000065	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. May repress NR5A1, PPARG, NR1H3, NR4A2, ESR1 and NR3C1 transcriptional activity. {ECO:0000269|PubMed:12920234}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.398
RVIS EVS: -0.11
RVIS percentile EVS: 45.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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