ZBTB42

protein-coding

zinc finger and BTB domain containing 42, the group of BTB domain containing|Zinc fingers C2H2-type

Gene summary

The protein encoded by this gene is a member of the C2H2 zinc finger protein family. This protein is predicted to have a pox virus and zinc finger (POZ) domain at the N-terminus and four zinc finger domains at the C-terminus. In human and mouse, the protein localizes to the nuclei of skeletal muscle cells. Knockdown of this gene in zebrafish results in abnormal skeletal muscle development and myofibrillar disorganization. A novel homozygous variant of the human gene has been associated with lethal congenital contracture syndrome, an autosomal recessive disorder that results in muscle wasting. [provided by RefSeq, Mar 2015]

MANE transcript

NM_001137601.3

Inheritance

ClinVar variants

U:61B:12

Top phenotype

Lethal congenital contracture syndrome 6

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr14:104,800,596-104,804,712

External References & Databases

Ensembl (ENSG00000179627)

NCBI Gene (100128927)

Transcript & Mutation Effects

hg38 • Region Span ~4.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lethal congenital contracture syndrome 6MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014549

Submitter: PanelApp Australia

lethal congenital contracture syndrome 6LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014549

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Lethal congenital contracture syndrome 6AR

Manifestation: Musculoskeletal

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: 25055871

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZBTB42 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 7

Lethal congenital contracture syndrome 6Total: 2

ZBTB42-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001137601.3. 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				7 clinvar	2 clinvar	9
missense			60 clinvar	2 clinvar	1 clinvar	63
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	61	9	3	73

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001137601.3	RefSeq	NP_001131073.1	1	MANE Select
ENST00000342537.8	Ensembl	ENSP00000409107.2	1	MANE Select
NM_001370342.1	RefSeq	NP_001357271.1	1	Standard
ENST00000555360.1	Ensembl	ENSP00000450673.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
zbtb42	Danio rerio	Structure: skeletal muscle cell Quality: atrophied abnormal

Gene / Model

Organism

Observed Phenotype

zbtb42

Danio rerio

Structure: skeletal muscle cell

Quality: atrophied

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
cellular response to DNA damage stimulus
muscle organ development

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342537
Coding exons: 1
Length: 4117
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.74	172	249	0.690	0.0000154	2682
Missense (PolyPhen)		48	91.052	0.52717		983
Synonymous	2.33	83	115	0.723	0.00000722	941
Loss of Function	2.57	3	13.0	0.231	9.27e-7	118

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. Specifically binds DNA and probably acts by recruiting chromatin remodeling multiprotein complexes. {ECO:0000250|UniProtKB:Q811H0}.;

Intolerance Scores

RVIS EVS: 0.77
RVIS percentile EVS: 86.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.193

Gene Damage Prediction

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