ZFHX4

zinc finger homeobox 4, the group of Zinc fingers C2H2-type|ZF class homeoboxes and pseudogenes

Basic information

Region (hg38): 8:76681239-76867281

Links

ENSG00000091656 ∙ NCBI:79776 ∙ OMIM:606940 ∙ HGNC:30939 ∙ Uniprot:Q86UP3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ptosis, hereditary congenital, 1 (No Known Disease Relationship), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFHX4 gene.

• not provided (2 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFHX4 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				45	19	64
missense			172	17	17	206
nonsense	1		4			5
start loss						0
frameshift	2	1	3			6
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				2		2
non coding						0
Total	3	2	179	62	36

Variants in ZFHX4

This is a list of pathogenic ClinVar variants found in the ZFHX4 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-76704110-C-A		not specified	Uncertain significance (Mar 30, 2024)
8-76704126-A-G		not specified	Uncertain significance (Jan 17, 2023)
8-76704140-A-C		not specified	Uncertain significance (Feb 16, 2023)
8-76704152-T-C		not specified	Uncertain significance (Sep 20, 2023)
8-76704161-A-G		not specified	Uncertain significance (Apr 07, 2023)
8-76704206-C-T		Neurodevelopmental disorder	Uncertain significance (Sep 02, 2022)
8-76704212-A-G		not specified	Uncertain significance (Nov 18, 2022)
8-76704221-A-C		not specified	Uncertain significance (Nov 22, 2021)
8-76704243-A-G		not specified	Uncertain significance (Mar 30, 2024)
8-76704247-G-C		ZFHX4-related disorder	Likely benign (Feb 20, 2019)
8-76704255-G-A		not specified	Uncertain significance (Aug 22, 2022)
8-76704266-G-A		not specified	Uncertain significance (Mar 30, 2024)
8-76704280-C-T			Benign (Dec 31, 2019)
8-76704284-G-A		ZFHX4-related disorder	Likely benign (Jan 01, 2024)
8-76704284-G-C		ZFHX4-related disorder	Benign (Jun 06, 2019)
8-76704288-A-G		not specified	Uncertain significance (Oct 29, 2021)
8-76704322-G-A		ZFHX4-related disorder	Likely benign (Aug 13, 2019)
8-76704329-C-A		not specified	Uncertain significance (Dec 27, 2023)
8-76704471-C-G		not specified	Uncertain significance (May 18, 2022)
8-76704525-A-T		not specified	Uncertain significance (May 18, 2023)
8-76704535-G-A		ZFHX4-related disorder	Likely benign (Apr 16, 2019)
8-76704566-C-T		not specified	Uncertain significance (Dec 27, 2023)
8-76704578-G-A			Benign/Likely benign (Aug 01, 2022)
8-76704618-G-A		not specified	Uncertain significance (Mar 30, 2024)
8-76704622-T-G		not specified	Uncertain significance (Mar 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFHX4	protein_coding	protein_coding	ENST00000521891	10	186068

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.07e-12	125464	0	23	125487	0.0000916

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	1831	1.96e+3	0.936	0.000108	23823
Missense in Polyphen		484	573.79	0.84351		6786
Synonymous	-0.866	812	781	1.04	0.0000494	6987
Loss of Function	9.19	10	118	0.0851	0.00000596	1491

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000151
Ashkenazi Jewish	0.00	0.00
East Asian	0.000112	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000126	0.000114
Middle Eastern	0.000112	0.000109
South Asian	0.0000327	0.0000327
Other	0.000361	0.000328

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in neural and muscle differentiation (By similarity). May be involved in transcriptional regulation. {ECO:0000250}.
• Pathway: Mesodermal Commitment Pathway;Ectoderm Differentiation (Consensus)

Recessive Scores

• pRec: 0.0890

Intolerance Scores

• loftool: 0.421
• rvis_EVS: -1.74
• rvis_percentile_EVS: 2.44

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.591
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.202

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfhx4

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;zinc ion binding;transcription regulatory region DNA binding