ZFAT

protein-coding

zinc finger and AT-hook domain containing, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

Previous symbols:

ZNF406
ZFAT1

MANE transcript

NM_020863.4

Inheritance

—

ClinVar variants

U:180B:24

Top phenotype

Autoimmune thyroid disease, susceptibility to, 3

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr8:134,477,788-134,713,049

External References & Databases

Ensembl (ENSG00000066827)

Transcript & Mutation Effects

hg38 • Region Span ~235.3 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 ZFAT variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 176

not providedTotal: 16

Autoimmune thyroid disease, susceptibility to, 3Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020863.4. 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			4 clinvar	4 clinvar	4 clinvar	12
missense			173 clinvar	12 clinvar	4 clinvar	189
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	180	16	8	204

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020863.4	RefSeq	NP_065914.2	16	MANE Select
ENST00000377838.8	Ensembl	ENSP00000367069.3	16	MANE Select
NM_001029939.4	RefSeq	NP_001025110.2	15	Standard
NM_001167583.3	RefSeq	NP_001161055.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

hematopoietic progenitor cell differentiation
regulation of transcription, DNA-templated
positive regulation of transcription by RNA polymerase II
spongiotrophoblast layer development

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
metal ion binding

Cellular Component

nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377838
Coding exons: 16
Length: 235262
Individuals with no LoFs: 124762
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 124806
p: 0.000176

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	602	723	0.833	0.0000417	8146
Missense (PolyPhen)		189	307.26	0.61511		3452
Synonymous	-0.651	314	300	1.05	0.0000196	2357
Loss of Function	3.66	22	50.0	0.440	0.00000243	657

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00028	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00024	0.00022	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation. Overexpression causes down-regulation of a number of genes involved in the immune response. Some genes are also up-regulated (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.586
RVIS EVS: -0.39
RVIS percentile EVS: 27.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.122

Gene Damage Prediction

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