BTN2A2

protein-coding

butyrophilin subfamily 2 member A2, the group of V-set domain containing|C2-set domain containing|Butyrophilins

Gene summary

Butyrophilin is the major protein associated with fat droplets in the milk. This gene is a member of the BTN2 subfamily of genes, which encode proteins belonging to the butyrophilin protein family. The gene is located in a cluster on chromosome 6, consisting of seven genes belonging to the expanding B7/butyrophilin-like group, a subset of the immunoglobulin gene superfamily. The encoded protein is a type I receptor glycoprotein involved in lipid, fatty-acid and sterol metabolism. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

MANE transcript

NM_006995.5

Inheritance

—

ClinVar variants

U:82B:22

Top phenotype

BTN2A2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr6:26,383,096-26,394,874

External References & Databases

Ensembl (ENSG00000124508)

Transcript & Mutation Effects

hg38 • Region Span ~11.8 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 BTN2A2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 84

BTN2A2-related disorderTotal: 17

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006995.5. 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	1 clinvar	6
missense			80 clinvar	8 clinvar	8 clinvar	96
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	82	13	9	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006995.5	RefSeq	NP_008926.2	7	MANE Select
ENST00000356709.9	Ensembl	ENSP00000349143.4	7	MANE Select
NM_001197237.2	RefSeq	NP_001184166.1	7	Standard
NM_001197238.2	RefSeq	NP_001184167.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Butyrophilin (BTN) family interactions
Immune System
Adaptive Immune System

Biological Process

negative regulation of phosphatidylinositol 3-kinase signaling
negative regulation of cellular metabolic process
positive regulation of regulatory T cell differentiation
negative regulation of activated T cell proliferation
negative regulation of cytokine secretion

Molecular Function

signaling receptor binding
protein binding

Cellular Component

plasma membrane
external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356709
Coding exons: 7
Length: 11779
Individuals with no LoFs: 125600
Homozygous LoFs: 1
Heterozygous LoFs: 147
Defined: 125748
p: 0.000589

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0390	295	293	1.01	0.0000163	3400
Missense (PolyPhen)		83	83.178	0.99786		1103
Synonymous	0.443	112	118	0.948	0.00000686	1058
Loss of Function	0.767	19	23.0	0.827	0.00000137	234

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00075	0.00075	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0011	0.0011	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.0020	0.0019	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits the proliferation of CD4 and CD8 T-cells activated by anti-CD3 antibodies, T-cell metabolism and IL2 and IFNG secretion. {ECO:0000250}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.889
RVIS EVS: 2.25
RVIS percentile EVS: 98.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.271

Gene Damage Prediction

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