VGLL2

protein-coding

vestigial like family member 2, the group of Vestigial like family

Gene summary

This gene encodes a protein with a transcriptional enhancer factor 1 (TEF-1) interaction domain. The encoded protein may act as a co-factor of TEF-1 regulated gene expression during skeletal muscle development. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

MANE transcript

NM_182645.3

Inheritance

ClinVar variants

U:60B:4

Top phenotype

isolated congenital syngnathia

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr6:117,265,558-117,273,565

External References & Databases

Ensembl (ENSG00000170162)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated congenital syngnathiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015409

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VGLL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182645.3. 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				1 clinvar	1 clinvar	2
missense			60 clinvar		2 clinvar	62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	60	1	3	64

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182645.3	RefSeq	NP_872586.1	4	MANE Select
ENST00000326274.6	Ensembl	ENSP00000320957.5	4	MANE Select
NM_153453.1	RefSeq	NP_703154.1	3	Standard
ENST00000352536.7	Ensembl	ENSP00000305405.5	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
vgll2a	Danio rerio	Structure: cranial neural crest cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

vgll2a

Danio rerio

Structure: cranial neural crest cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

skeletal muscle tissue development
positive regulation of transcription by RNA polymerase II

Molecular Function

transcription coactivator activity
protein binding
protein C-terminus binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000326274
Coding exons: 4
Length: 8008
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125747
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.117	121	125	0.970	0.00000565	2010
Missense (PolyPhen)		49	44.442	1.1026		712
Synonymous	0.440	49	53.1	0.923	0.00000249	644
Loss of Function	2.35	1	8.32	0.120	3.57e-7	121

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	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a specific coactivator for the mammalian TEFs. May play a role in the development of skeletal muscles.;

Recessive Scores

pRec: 0.118

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.561

Gene Damage Prediction

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