BTNL2

Chr 6AD

butyrophilin like 2

Also known as: BTL-II, BTN7, HSBLMHC1, SS2

NCBI Gene: 56244ENSG00000204290UniProt: Q9UIR0

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]

Primary Disease Associations & Inheritance

{Sarcoidosis, susceptibility to, 2}MIM #612387
AD
UniProtSarcoidosis 2
71
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BTNL2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 55 VUS of 71 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.30LOEUF
pLI 0.000
Z-score 0.55
OE 0.87 (0.59–1.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.50Z-score
OE missense 0.74 (0.66–0.83)
194 obs / 262.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.87 (0.59–1.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.66–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 17 / 19.6Missense obs/exp: 194 / 262.6Syn Z: 0.89

ClinVar Variant Classifications

71 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS55
Likely Benign5
Benign6
4
Pathogenic
1
Likely Pathogenic
55
VUS
5
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
36
18
1
55
Likely Benign
0
3
2
0
5
Benign
1
3
1
1
6
Total14226271

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BTNL2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Sarcoidosis, susceptibility to, 2}

MIM #612387

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics of sarcoidosis.
Spagnolo P et al.·Clin Dermatol
2007Review
[Pathogenesis of sarcoidosis].
Pacheco Y·Rev Med Interne
2011Review
Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease.
Zhou F et al.·Nat Genet
2016
Granuloma genes in sarcoidosis: what is new?
Fischer A et al.·Curr Opin Pulm Med
2015Review
Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort.
Pacheco Y et al.·Orphanet J Rare Dis
2016Cohort
Correlation analysis of the HLA-DPB1*05:01 and BTNL2 genes within the histocompatibility complex region with a clinical phenotype of psoriasis vulgaris in the Chinese Han population.
Guo H et al.·J Gene Med
2017
Genetic factors in OA pathogenesis.
Chapman K et al.·Bone
2012Review
BTNL2 gene variant and sarcoidosis.
Li Y et al.·Thorax
2006
BTNL2 gene polymorphism associations with susceptibility and phenotype expression in sarcoidosis.
Morais A et al.·Respir Med
2012
BTNL2 allele associations with chronic beryllium disease in HLA-DPB1*Glu69-negative individuals.
Sato H et al.·Tissue Antigens
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools