BTG4

protein-coding

BTG anti-proliferation factor 4, the group of BTG/Tob family|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein can induce G1 arrest in the cell cycle. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001367975.1

Inheritance

ClinVar variants

P:5U:33B:1

Top phenotype

Oocyte/zygote/embryo maturation arrest 8

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr11:111,467,526-111,514,367

External References & Databases

Ensembl (ENSG00000137707)

Transcript & Mutation Effects

hg38 • Region Span ~46.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oocyte maturation defect 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033564

Submitter: PanelApp Australia

female infertilityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0021124

Submitter: Franklin by Genoox

whole-exome sequencing (WES) to identify four homozygous pathogenic variants in BTG4 that are responsible for human ZCF in four independent families. In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals. https://doi.org/10.1016/j.ajhg.2020.05.010

oocyte maturation defect 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033564

Submitter: Labcorp Genetics (formerly Invitae)

oocyte maturation defect 8LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0033564

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Oocyte/zygote/embryo maturation arrest 8AR

Manifestation: Obstetric

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: 32502391

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BTG4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 32

Oocyte maturation defect 8Total: 5

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001367975.1. 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			1
missense	1 clinvar	1 clinvar	32 clinvar	1 clinvar		35
nonsense		1 clinvar				1
start loss	1 clinvar					1
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	3	2	33	1	0	39

Highest pathogenic variant AF is 0.0000065684035

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001367975.1	RefSeq	NP_001354904.1	4	MANE Select
ENST00000692032.1	Ensembl	ENSP00000509850.1	4	MANE Select
NM_001367974.1	RefSeq	NP_001354903.1	4	Standard
NM_001367976.1	RefSeq	NP_001354905.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA degradation - Homo sapiens (human)

Biological Process

cell cycle arrest
negative regulation of cell population proliferation
neuron differentiation
negative regulation of mitotic cell cycle

Cellular Component

cellular_component
nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356018
Coding exons: 5
Length: 44829
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125736
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.241	111	118	0.938	0.00000621	1490
Missense (PolyPhen)		39	39.59	0.9851		503
Synonymous	-0.261	44	41.9	1.05	0.00000234	389
Loss of Function	2.15	3	10.5	0.285	4.44e-7	134

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Shows marked antiproliferative activity, being able to induce G(1) arrest.;

Recessive Scores

pRec: 0.137

Intolerance Scores

LoFtool: 0.307
RVIS EVS: -0.3
RVIS percentile EVS: 32.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.864

Gene Damage Prediction

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