ZNF646

protein-coding

zinc finger protein 646, the group of Zinc fingers C2H2-type

Gene summary

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014699.4

Inheritance

—

ClinVar variants

U:311B:24

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr16:31,074,422-31,084,196

External References & Databases

Ensembl (ENSG00000167395)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 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 ZNF646 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 325

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014699.4. 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	3 clinvar		4
missense			309 clinvar	21 clinvar		330
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	311	24	0	335

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014699.4	RefSeq	NP_055514.3	2	MANE Select
ENST00000300850.5	Ensembl	ENSP00000300850.5	2	MANE Select
ENST00000394979.2	Ensembl	ENSP00000378429.2	1	Standard
ENST00000428260.1	Ensembl	ENSP00000391271.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
regulation of transcription by RNA polymerase II

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300850
Coding exons: 2
Length: 9775
Individuals with no LoFs: 125689
Homozygous LoFs: 0
Heterozygous LoFs: 59
Defined: 125748
p: 0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.638	1080	1.14e+3	0.947	0.0000724	11951
Missense (PolyPhen)		381	447.35	0.85168		4628
Synonymous	-0.683	454	436	1.04	0.0000243	3789
Loss of Function	4.37	19	53.5	0.355	0.00000320	590

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00034	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00033	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.0960

Intolerance Scores

LoFtool: 0.534
RVIS EVS: 0.23
RVIS percentile EVS: 68.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.966

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High