ZNF681

protein-coding

zinc finger protein 681, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a protein containing the krueppel associated box (KRAB) and zinc-finger domains, which may be involved in transcriptional regulation. Non-functional alleles of this gene are present in alternate genome assemblies including T2T-CHM13v1.1, resulting from a 'TG' deletion (rs61397759) which causes a frameshift and a premature stop codon. [provided by RefSeq, Sep 2022]

MANE transcript

NM_138286.3

Inheritance

—

ClinVar variants

U:84B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr19:23,739,195-23,758,891

External References & Databases

Ensembl (ENSG00000196172)

Transcript & Mutation Effects

hg38 • Region Span ~19.7 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 ZNF681 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 88

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138286.3. 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						0
missense			84 clinvar	5 clinvar		89
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	84	5	0	89

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138286.3	RefSeq	NP_612143.2	4	MANE Select
ENST00000402377.3	Ensembl	ENSP00000384000.3	4	MANE Select
ENST00000528059.1	Ensembl	ENSP00000433806.1	2	Standard
ENST00000531570.1	Ensembl	ENSP00000435824.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402377
Coding exons: 4
Length: 19697
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125741
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.865	355	312	1.14	0.0000139	4257
Missense (PolyPhen)		73	70.184	1.0401		929
Synonymous	-0.434	114	108	1.05	0.00000497	1097
Loss of Function	0.544	4	5.36	0.746	2.28e-7	64

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.754
RVIS EVS: 1
RVIS percentile EVS: 90.69

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.224

Gene Damage Prediction

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