ZHX2

protein-coding

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

Gene summary

The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014943.5

Inheritance

—

ClinVar variants

U:130B:12

Top phenotype

Hirschsprung disease, susceptibility to, 1

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr8:122,781,655-122,974,510

External References & Databases

Ensembl (ENSG00000178764)

Transcript & Mutation Effects

hg38 • Region Span ~192.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZHX2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 132

not providedTotal: 8

Hirschsprung disease, susceptibility to, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014943.5. 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				3 clinvar	4 clinvar	7
missense			129 clinvar	4 clinvar	1 clinvar	134
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	130	7	5	142

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014943.5	RefSeq	NP_055758.1	1	MANE Select
ENST00000314393.6	Ensembl	ENSP00000314709.4	1	MANE Select
NM_001362797.2	RefSeq	NP_001349726.1	1	Standard
NM_001412796.1	RefSeq	NP_001399725.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
mRNA catabolic process
somatic stem cell population maintenance
negative regulation of neuron differentiation
negative regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
transcription corepressor activity
protein binding

Cellular Component

nucleus
nucleoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314393
Coding exons: 1
Length: 193118
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125747
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.759	452	500	0.904	0.0000316	5479
Missense (PolyPhen)		121	183.4	0.65976		2126
Synonymous	-1.51	244	216	1.13	0.0000160	1697
Loss of Function	3.49	8	27.9	0.287	0.00000155	309

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a transcriptional repressor. Represses the promoter activity of the CDC25C gene stimulated by NFYA. {ECO:0000269|PubMed:12741956}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.0883
RVIS EVS: -1.1
RVIS percentile EVS: 6.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.943

Gene Damage Prediction

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