ZNF446

protein-coding

zinc finger protein 446, the group of Zinc fingers C2H2-type|SCAN domain containing

Gene summary

Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_017908.4

Inheritance

—

ClinVar variants

P:1U:104B:5

Top phenotype

Short stature

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr19:58,474,017-58,481,230

External References & Databases

Ensembl (ENSG00000083838)

Transcript & Mutation Effects

hg38 • Region Span ~7.2 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 ZNF446 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 99

Short statureTotal: 3

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017908.4. 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				2 clinvar		2
missense			103 clinvar	3 clinvar		106
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	104	5	0	110

Highest pathogenic variant AF is 0.000028522143

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017908.4	RefSeq	NP_060378.1	6	MANE Select
ENST00000594369.6	Ensembl	ENSP00000472802.1	6	MANE Select
NM_001304453.1	RefSeq	NP_001291382.1	6	Standard
ENST00000335841.8	Ensembl	ENSP00000336565.4	5	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

extracellular space
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000594369
Coding exons: 6
Length: 7214
Individuals with no LoFs: 125663
Homozygous LoFs: 0
Heterozygous LoFs: 80
Defined: 125743
p: 0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.583	312	284	1.10	0.0000179	2835
Missense (PolyPhen)		80	75.902	1.054		819
Synonymous	-1.54	144	122	1.18	0.00000777	960
Loss of Function	1.20	14	19.8	0.708	0.00000110	191

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00049	0.00049	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00046	0.00044	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Intolerance Scores

LoFtool: 0.807
RVIS EVS: 0.22
RVIS percentile EVS: 68.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.733

Gene Damage Prediction

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