CD81

protein-coding

CD81 molecule, the group of Tetraspanins|CD molecules

Gene summary

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This protein appears to promote muscle cell fusion and support myotube maintenance. Also it may be involved in signal transduction. This gene is localized in the tumor-suppressor gene region and thus it is a candidate gene for malignancies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

Previous symbols:

TAPA1

MANE transcript

NM_004356.4

Inheritance

ClinVar variants

P:1U:115B:77

Top phenotype

Immunodeficiency, common variable, 6

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr11:2,376,177-2,397,802

External References & Databases

Ensembl (ENSG00000110651)

Transcript & Mutation Effects

hg38 • Region Span ~21.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency, common variable, 6LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013286

Submitter: ClinGen

CD81 was first reported in relation to autosomal recessive common variable immunodeficiency in 2010 (van Zelm et al., PMID: 25739915). This single case report described a homozygous splice variant predicted to undergo NMD that was present in the heterozygous state in both unaffected parents and one unaffected sibling. Expression of CD81 and CD19 was found to be absent on the patient's B cells and reduced for familial carriers.This gene-disease relationship is further supported by protein interactions (Bradbury et al., 1992, PMID: 1383329), boichemical function (Tedder, et al., 1997, PMID: 9047233), and expression analysis (Oren, et al., 1990, PMID: 1695320). Three independent CD81-knockout mice were found to partially recapitulate the cellular and molecular phenotype seen in the human patient, but did not exhibit an overlapping clinical phenotype (Miyazaki, et al., 1997, PMID: 9250665, Tsitsikov, et al., 1997, PMID: 9380722, Maecker, et al., 1997, PMID: 9126932). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.

immunodeficiency, common variable, 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013286

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Immunodeficiency, common variable, 6AR

Manifestation: Allergy/Immunology/Infectious; Renal

Intervention: Allergy/Immunology/Infectious

Rationale: Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial

Refs: 20237408

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD81 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 278

not specifiedTotal: 57

Immunodeficiency, common variable, 6Total: 11

CD81-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004356.4. 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			5 clinvar	74 clinvar	1 clinvar	80
missense			102 clinvar	2 clinvar		104
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	1	0	115	76	1	193

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004356.4	RefSeq	NP_004347.1	8	MANE Select
ENST00000263645.10	Ensembl	ENSP00000263645.5	8	MANE Select
NM_001297649.2	RefSeq	NP_001284578.1	6	Standard
NM_001425129.1	RefSeq	NP_001412058.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

B cell receptor signaling pathway - Homo sapiens (human)
Malaria - Homo sapiens (human)
Hepatitis C - Homo sapiens (human)
B Cell Receptor Signaling Pathway
Innate Immune System

Biological Process

activation of MAPK activity
cell surface receptor signaling pathway
protein localization
cell population proliferation
positive regulation of cell population proliferation

Molecular Function

virus receptor activity
integrin binding
protein binding
MHC class II protein complex binding
transferrin receptor binding

Cellular Component

immunological synapse
plasma membrane
integral component of plasma membrane
focal adhesion
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263645
Coding exons: 8
Length: 21243
Individuals with no LoFs: 125029
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125030
p: 0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.806	110	137	0.806	0.00000858	1545
Missense (PolyPhen)		39	67.17	0.58062		719
Synonymous	-2.04	79	59.0	1.34	0.00000437	445
Loss of Function	3.01	1	12.4	0.0804	5.42e-7	149

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
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: May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV.;
Disease: DISEASE: Immunodeficiency, common variable, 6 (CVID6) [MIM:613496]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269|PubMed:20237408}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.392

Intolerance Scores

LoFtool: 0.219
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.660

Gene Damage Prediction

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