FEZF1

FEZ family zinc finger 1, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 7:122301303-122310691

Previous symbols: [ "ZNF312B" ]

Links

ENSG00000128610 ∙ NCBI:389549 ∙ OMIM:613301 ∙ HGNC:22788 ∙ Uniprot:A0PJY2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism 22 with or without anosmia (Strong), mode of inheritance: AR
• hypogonadotropic hypogonadism 22 with or without anosmia (Moderate), mode of inheritance: AR
• Kallmann syndrome (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 22 with or without anosmia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 22 with or without anosmia	AR	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Endocrine; Neurologic	25192046

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FEZF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FEZF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				18	1	19
missense			32	5		37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding				13	16	29
Total	0	0	32	36	17

Variants in FEZF1

This is a list of pathogenic ClinVar variants found in the FEZF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-122301727-T-TA			Likely benign (Nov 22, 2019)
7-122302003-G-A			Likely benign (Jun 23, 2023)
7-122302008-C-T		Inborn genetic diseases	Uncertain significance (Jul 30, 2023)
7-122302010-T-C		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
7-122302028-A-C		Inborn genetic diseases	Uncertain significance (May 14, 2024)
7-122302032-G-A		Inborn genetic diseases	Uncertain significance (May 13, 2024)
7-122302032-G-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2021)
7-122302052-G-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
7-122302075-C-T		not specified • FEZF1-related disorder	Benign (Mar 12, 2022)
7-122302076-G-A		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
7-122302082-T-G		Amenorrhea	Likely benign (Dec 10, 2018)
7-122302102-C-T		FEZF1-related disorder	Likely benign (Mar 22, 2023)
7-122302107-C-G			Uncertain significance (Jul 30, 2022)
7-122302205-T-C		Inborn genetic diseases	Uncertain significance (Jun 22, 2024)
7-122302239-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
7-122302261-G-A		not specified • FEZF1-related disorder	Benign/Likely benign (Dec 23, 2021)
7-122302261-G-C			Likely benign (Dec 21, 2023)
7-122302301-T-G		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
7-122302388-GA-G			Benign (Oct 21, 2018)
7-122302472-A-G			Benign (Jun 28, 2019)
7-122302567-A-G			Benign (Aug 09, 2018)
7-122302620-C-A			Benign (Aug 09, 2018)
7-122302778-G-GACA			Benign (Mar 31, 2019)
7-122302784-T-C			Benign (Dec 12, 2023)
7-122302793-G-C			Benign (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FEZF1	protein_coding	protein_coding	ENST00000442488	4	9298

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.950	0.0495	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	210	270	0.779	0.0000121	3110
Missense in Polyphen		63	102.02	0.61755		1263
Synonymous	0.162	113	115	0.981	0.00000548	957
Loss of Function	3.20	1	13.9	0.0722	6.07e-7	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000441	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription repressor. Involved in the axonal projection and proper termination of olfactory sensory neurons (OSN). Plays a role in rostro-caudal patterning of the diencephalon and in prethalamic formation. Expression is required in OSN to cell-autonomously regulate OSN axon projections. Regulates non-cell-autonomously the layer formation of the olfactory bulb development and the interneurons. May be required for correct rostral migration of the interneuron progenitors (By similarity). {ECO:0000250}.
• Pathway: Olfactory bulb development and olfactory learning (Consensus)

Recessive Scores

• pRec: 0.0948

Intolerance Scores

• loftool: 0.395
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.354
• hipred: Y
• hipred_score: 0.808
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.887

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fezf1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cellular phenotype; craniofacial phenotype; taste/olfaction phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: fezf1
• Affected structure: hypothalamus development
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neuron migration;axon guidance;negative regulation of cell population proliferation;olfactory bulb development;forebrain anterior/posterior pattern specification;cell dedifferentiation;positive regulation of neuron differentiation;positive regulation of transcription, DNA-templated
• Cellular component: nucleus;cytosol
• Molecular function: 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;metal ion binding