ZBTB40

protein-coding

zinc finger and BTB domain containing 40, the group of BTB domain containing|Zinc fingers C2H2-type

Gene summary

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Involved in DNA damage response. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014870.4

Inheritance

ClinVar variants

U:151B:24

Top phenotype

ZBTB40-related disorder

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr1:22,428,838-22,531,157

External References & Databases

Ensembl (ENSG00000184677)

Transcript & Mutation Effects

hg38 • Region Span ~102.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZBTB40 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 161

ZBTB40-related disorderTotal: 8

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014870.4. 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			1 clinvar	9 clinvar	2 clinvar	12
missense			147 clinvar	12 clinvar	1 clinvar	160
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	151	21	3	175

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014870.4	RefSeq	NP_055685.3	17	MANE Select
ENST00000375647.5	Ensembl	ENSP00000364798.4	17	MANE Select
NM_001083621.2	RefSeq	NP_001077090.1	17	Standard
NM_001330398.2	RefSeq	NP_001317327.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
cellular response to DNA damage stimulus
bone mineralization

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404138
Coding exons: 17
Length: 79307
Individuals with no LoFs: 125637
Homozygous LoFs: 1
Heterozygous LoFs: 110
Defined: 125748
p: 0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	564	642	0.878	0.0000352	8146
Missense (PolyPhen)		14	22.935	0.61043		259
Synonymous	0.300	255	261	0.976	0.0000154	2395
Loss of Function	3.31	25	50.4	0.496	0.00000246	678

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00043	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00071	0.00069	rare
South Asian	0.00033	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.524
RVIS EVS: -0.64
RVIS percentile EVS: 16.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.250

Gene Damage Prediction

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