ZHX3

protein-coding

zinc fingers and homeoboxes 3, the group of ZF class homeoboxes and pseudogenes|Zinc fingers C2H2-type

Gene summary

This gene encodes a member of the zinc fingers and homeoboxes (ZHX) gene family. The encoded protein contains two C2H2-type zinc fingers and five homeodomains and forms a dimer with itself or with zinc fingers and homeoboxes family member 1. In the nucleus, the dimerized protein interacts with the A subunit of the ubiquitous transcription factor nuclear factor-Y and may function as a transcriptional repressor. [provided by RefSeq, Jul 2008]

Previous symbols:

TIX1

MANE transcript

NM_001384317.1

Inheritance

—

ClinVar variants

U:170B:70

Top phenotype

ZHX3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr20:41,178,448-41,317,731

External References & Databases

Ensembl (ENSG00000174306)

Transcript & Mutation Effects

hg38 • Region Span ~139.3 kb

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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 ZHX3 variants in ClinVar

3 Conditions Cataloged

not providedTotal: 150

not specifiedTotal: 116

ZHX3-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001384317.1. 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			2 clinvar	52 clinvar	7 clinvar	61
missense			166 clinvar	7 clinvar	4 clinvar	177
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	170	59	11	240

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001384317.1	RefSeq	NP_001371246.1	2	MANE Select
ENST00000683867.1	Ensembl	ENSP00000506788.1	2	MANE Select
NM_001384315.1	RefSeq	NP_001371244.1	2	Standard
NM_001384316.1	RefSeq	NP_001371245.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
cell differentiation
positive regulation of osteoblast differentiation
negative regulation of transcription, DNA-templated

Molecular Function

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

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309060
Coding exons: 2
Length: 139225
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125746
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.46	439	534	0.823	0.0000296	6293
Missense (PolyPhen)		113	185.74	0.60838		2220
Synonymous	0.168	213	216	0.985	0.0000126	1938
Loss of Function	3.61	8	29.0	0.276	0.00000164	334

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000072	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a transcriptional repressor. Involved in the early stages of mesenchymal stem cell (MSC) osteogenic differentiation. Is a regulator of podocyte gene expression during primary glomerula disease. Binds to promoter DNA. {ECO:0000269|PubMed:12659632, ECO:0000269|PubMed:21174497}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.291
RVIS EVS: -0.2
RVIS percentile EVS: 39.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.875

Gene Damage Prediction

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