ZNF668

protein-coding

zinc finger protein 668, the group of Zinc fingers C2H2-type

Gene summary

Predicted to enable transcription cis-regulatory region binding activity. Involved in DNA repair. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_024706.5

Inheritance

ClinVar variants

P:3U:83B:9

Top phenotype

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr16:31,060,843-31,074,240

External References & Databases

Ensembl (ENSG00000167394)

Transcript & Mutation Effects

hg38 • Region Span ~13.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with poor growth, large ears, and dysmorphic faciesLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859350

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with poor growth, large ears, and dysmorphic faciesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859350

Submitter: PanelApp Australia

neurodevelopmental disorder with poor growth, large ears, and dysmorphic faciesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859350

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic faciesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 26633546; 34313816

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF668 variants in ClinVar

11 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 6

ZNF668-related disorderTotal: 5

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic faciesTotal: 4

Profound global developmental delayTotal: 2

Progressive microcephalyTotal: 2

marked facial dysmorphismTotal: 2

Failure to thriveTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024706.5. 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			1 clinvar	6 clinvar	1 clinvar	8
missense			79 clinvar	2 clinvar		81
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	2	1	83	8	1	95

Highest pathogenic variant AF is 6.203174e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024706.5	RefSeq	NP_078982.3	2	MANE Select
ENST00000300849.5	Ensembl	ENSP00000300849.4	2	MANE Select
NM_001172668.2	RefSeq	NP_001166139.1	2	Standard
NM_001172669.2	RefSeq	NP_001166140.1	3	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

negative regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor 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: ENST00000539836
Coding exons: 3
Length: 13478
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125740
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.35	326	469	0.695	0.0000358	4080
Missense (PolyPhen)		76	168.42	0.45126		1487
Synonymous	0.630	194	206	0.944	0.0000167	1353
Loss of Function	3.14	5	20.2	0.247	0.00000110	224

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000073	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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

Intolerance Scores

LoFtool: 0.634
RVIS EVS: -0.51
RVIS percentile EVS: 21.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.919

Gene Damage Prediction

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