FEZF2

protein-coding

FEZ family zinc finger 2, the group of Zinc fingers C2H2-type

Gene summary

Predicted to enable several functions, including DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and zinc ion binding activity. Predicted to be involved in regulation of gene expression. Predicted to act upstream of or within several processes, including negative regulation of transcription by RNA polymerase II; nervous system development; and regulation of neuron differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2025]

Previous symbols:

ZNF312

MANE transcript

NM_018008.4

Inheritance

ClinVar variants

P:7U:69B:2

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:62,369,681-62,374,324

External References & Databases

Ensembl (ENSG00000153266)

Transcript & Mutation Effects

hg38 • Region Span ~4.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FEZF2 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 29

FEZF2-related disorderTotal: 8

Neurodevelopmental disorderTotal: 1

Hypomyelination and Congenital CataractTotal: 1

FEZF2-related neurodevelopmental disorderTotal: 1

Neurodevelopmental phenotypeTotal: 1

FEZF2-related neurodevelopmental conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018008.4. 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		1 clinvar	63 clinvar			64
nonsense	2 clinvar	1 clinvar	1 clinvar			4
start loss						0
frameshift		3 clinvar	4 clinvar			7
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	5	69	2	0	78

Highest pathogenic variant AF is 0.0000017283814

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018008.4	RefSeq	NP_060478.3	4	MANE Select
ENST00000283268.8	Ensembl	ENSP00000283268.3	4	MANE Select
ENST00000475839.1	Ensembl	ENSP00000418804.1	4	Standard
ENST00000475839.2	Ensembl	ENSP00000418804.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fezf2	Danio rerio	Structure: whole organism Quality: dead abnormal

Gene / Model

Organism

Observed Phenotype

fezf2

Danio rerio

Structure: whole organism

Quality: dead

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
axon guidance
axonal fasciculation
locomotory behavior
negative regulation of cell population proliferation

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000283268
Coding exons: 4
Length: 4644
Individuals with no LoFs: 112048
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 112049
p: 0.00000446

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.07	156	248	0.629	0.0000113	2930
Missense (PolyPhen)		16	51.777	0.30902		537
Synonymous	-1.51	131	111	1.18	0.00000543	942
Loss of Function	3.40	0	13.5	0.00	5.73e-7	175

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000033	0.000033	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription repressor. Required for the specification of corticospinal motor neurons and other subcerebral projection neurons. May play a role in layer and neuronal subtype-specific patterning of subcortical projections and axonal fasciculation. Controls the development of dendritic arborization and spines of large layer V pyramidal neurons. May be involved in innate immunity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

RVIS EVS: -0.19
RVIS percentile EVS: 39.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.630

Gene Damage Prediction

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