ZFHX2

zinc finger homeobox 2, the group of Zinc fingers C2H2-type|ZF class homeoboxes and pseudogenes

Basic information

Region (hg38): 14:23520857-23556192

Previous symbols: [ "ZNF409" ]

Links

ENSG00000136367 ∙ NCBI:85446 ∙ OMIM:617828 ∙ HGNC:20152 ∙ Uniprot:Q9C0A1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• indifference to pain, congenital, autosomal dominant (Limited), mode of inheritance: AD
• indifference to pain, congenital, autosomal dominant (Limited), mode of inheritance: AD
• indifference to pain, congenital, autosomal dominant (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Marsili syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	29253101
Insensitivity to pain can result in injuries

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFHX2 gene.

• not_specified (436 variants)
• not_provided (77 variants)
• ZFHX2-related_disorder (42 variants)
• Indifference_to_pain,_congenital,_autosomal_dominant (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFHX2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000033400.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	51	7	60
missense	1		418	35	9	463
nonsense						0
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)						0
Total	1	0	421	86	16

Highest pathogenic variant AF is 0.0000021673732

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFHX2	protein_coding	protein_coding	ENST00000419474	9	35336

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00289	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.95	983	1.28e+3	0.768	0.0000713	16267
Missense in Polyphen		315	474.42	0.66397		5894
Synonymous	3.65	412	518	0.796	0.0000281	5582
Loss of Function	6.07	10	61.3	0.163	0.00000322	850

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	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

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

Recessive Scores

• pRec: 0.0969

Haploinsufficiency Scores

• pHI: 0.266
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.192

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfhx2

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;adult behavior;positive regulation of transcription, DNA-templated;regulation of sensory perception of pain
• 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