BTNL2

protein-coding

butyrophilin like 2, the group of V-set domain containing|C2-set domain containing|Butyrophilins

Gene summary

This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

MANE transcript

NM_001304561.2

Inheritance

ClinVar variants

U:43B:8

Top phenotype

BTNL2-related condition

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr6:32,393,339-32,407,181

External References & Databases

Ensembl (ENSG00000204290)

Transcript & Mutation Effects

hg38 • Region Span ~13.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

sarcoidosis, susceptibility to, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012888

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BTNL2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 8

BTNL2-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001304561.2. 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			2 clinvar		1 clinvar	3
missense			39 clinvar	3 clinvar	3 clinvar	45
nonsense			1 clinvar		1 clinvar	2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	43	3	5	51

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001304561.2	RefSeq	NP_001291490.1	7	MANE Select
ENST00000454136.8	Ensembl	ENSP00000390613.3	7	MANE Select
ENST00000446536.3	Ensembl	ENSP00000388434.2	2	Standard
ENST00000465865.6	Ensembl	ENSP00000420063.1	3	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

regulation of immune response
T cell receptor signaling pathway

Molecular Function

signaling receptor 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: ENST00000454136
Coding exons: 7
Length: 13166
Individuals with no LoFs: 100966
Homozygous LoFs: 1860
Heterozygous LoFs: 22922
Defined: 125748
p: 0.104

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.50	194	263	0.739	0.0000135	3104
Missense (PolyPhen)		59	85.132	0.69304		1087
Synonymous	0.885	98	110	0.893	0.00000648	950
Loss of Function	0.546	17	19.6	0.867	8.40e-7	231

Population LoF Frequency

Population	CAF	p-value	Status
African	0.16	0.15	notable
Latino/Admixed American	0.19	0.18	notable
Ashkenazi Jewish	0.033	0.033	notable
East Asian	0.19	0.19	notable
Finnish	0.17	0.16	notable
European (Non-Finnish)	0.071	0.066	notable
South Asian	0.085	0.081	notable
Other	0.10	0.097	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negative regulator of T-cell proliferation. {ECO:0000250}.;
Disease: DISEASE: Sarcoidosis 2 (SS2) [MIM:612387]: An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. {ECO:0000269|PubMed:15735647}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A nucleotide transition affecting a splice donor site results in the use of an alternative splice site and the production of isoform 3. Individuals expressing isoform 3 have a higher risk for sarcoidosis.;

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0448

Gene Damage Prediction

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