CD276

protein-coding

CD276 molecule, the group of V-set domain containing|CD molecules|C2-set domain containing|B7 family

Gene summary

The protein encoded by this gene belongs to the immunoglobulin superfamily, and thought to participate in the regulation of T-cell-mediated immune response. Studies show that while the transcript of this gene is ubiquitously expressed in normal tissues and solid tumors, the protein is preferentially expressed only in tumor tissues. Additionally, it was observed that the 3' UTR of this transcript contains a target site for miR29 microRNA, and there is an inverse correlation between the expression of this protein and miR29 levels, suggesting regulation of expression of this gene product by miR29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

MANE transcript

NM_001024736.2

Inheritance

—

ClinVar variants

U:112B:4

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr15:73,683,966-73,714,514

External References & Databases

Ensembl (ENSG00000103855)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 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 CD276 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 3

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001024736.2. 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			104 clinvar	3 clinvar		107
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	112	3	1	116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001024736.2	RefSeq	NP_001019907.1	9	MANE Select
ENST00000318443.10	Ensembl	ENSP00000320084.5	9	MANE Select
NM_001329628.2	RefSeq	NP_001316557.1	7	Standard
NM_001329629.2	RefSeq	NP_001316558.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)

Biological Process

immune response
cell population proliferation
positive regulation of T cell proliferation
T cell activation
positive regulation of interferon-gamma biosynthetic process

Molecular Function

signaling receptor binding
protein binding

Cellular Component

external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318443
Coding exons: 9
Length: 30553
Individuals with no LoFs: 125552
Homozygous LoFs: 0
Heterozygous LoFs: 196
Defined: 125748
p: 0.000780

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0486	342	345	0.993	0.0000225	3432
Missense (PolyPhen)		129	138.37	0.93228		1413
Synonymous	-1.79	185	157	1.18	0.0000111	1131
Loss of Function	1.04	16	21.2	0.756	9.15e-7	222

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0012	0.00087	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0010	0.0010	notable
Finnish	0.0017	0.0017	notable
European (Non-Finnish)	0.00061	0.00061	rare
South Asian	0.0010	0.0010	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling. {ECO:0000269|PubMed:11224528, ECO:0000269|PubMed:12906861, ECO:0000269|PubMed:14764704, ECO:0000269|PubMed:15314238, ECO:0000269|PubMed:15682454, ECO:0000269|PubMed:15961727}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.838
RVIS EVS: 0.45
RVIS percentile EVS: 78.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.707

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High