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
neurodevelopmental disorder (Moderate), mode of inheritance: AD
neurodevelopmental disorder (Definitive), mode of inheritance: AD
orofacial cleft (Limited), mode of inheritance: AD
complex neurodevelopmental disorder (Moderate), mode of inheritance: AD

ClinVar

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

not_specified (431 variants)
not_provided (154 variants)
ZFHX4-related_disorder (60 variants)
Ptosis,_hereditary_congenital,_1 (7 variants)
Neurodevelopmental_disorder (5 variants)
ZFHX4-related_syndrome (1 variants)
ZFHX4-associated_neurodevelopmental_disorder (1 variants)
Congenital_corneal_opacity (1 variants)
Usher_syndrome_type_1F (1 variants)
See_cases (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. These statistics are base on transcript: NM_000024721.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	55 clinvar	18 clinvar	74
missense			449 clinvar	40 clinvar	16 clinvar	505
nonsense	1 clinvar	2 clinvar	17 clinvar			20
start loss						0
frameshift	3 clinvar	2 clinvar	20 clinvar			25
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	4	5	488	95	34

Highest pathogenic variant AF is 0.0000065734985

Loading clinvar variants...

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
Phenotype

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