TPBG

protein-coding

trophoblast glycoprotein

Gene summary

This gene encodes a leucine-rich transmembrane glycoprotein that may be involved in cell adhesion. The encoded protein is an oncofetal antigen that is specific to trophoblast cells. In adults this protein is highly expressed in many tumor cells and is associated with poor clinical outcome in numerous cancers. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]

MANE transcript

NM_001376922.1

Inheritance

—

ClinVar variants

U:56B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr6:82,363,206-82,367,420

External References & Databases

Ensembl (ENSG00000146242)

Transcript & Mutation Effects

hg38 • Region Span ~4.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TPBG variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001376922.1. 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						0
missense			56 clinvar	4 clinvar		60
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	56	4	0	60

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001376922.1	RefSeq	NP_001363851.1	1	MANE Select
ENST00000369750.4	Ensembl	ENSP00000358765.4	1	MANE Select
NM_001166392.2	RefSeq	NP_001159864.1	1	Standard
NM_006670.5	RefSeq	NP_006661.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-Core

Biological Process

cell adhesion
positive regulation of synapse assembly

Cellular Component

endoplasmic reticulum
integral component of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369750
Coding exons: 1
Length: 7623
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0673	234	237	0.988	0.0000119	2670
Missense (PolyPhen)		51	74.984	0.68014		929
Synonymous	-3.51	155	109	1.43	0.00000560	934
Loss of Function	1.28	4	7.88	0.508	3.36e-7	91

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as an inhibitor of Wnt/beta-catenin signaling by indirectly interacting with LRP6 and blocking Wnt3a- dependent LRP6 internalization. {ECO:0000269|PubMed:22100263}.;

Recessive Scores

pRec: 0.129

Intolerance Scores

LoFtool: 0.296
RVIS EVS: -0.2
RVIS percentile EVS: 38.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.880

Gene Damage Prediction

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