BTNL8

protein-coding

butyrophilin like 8, the group of V-set domain containing|Butyrophilins

Gene summary

Predicted to enable signaling receptor binding activity. Involved in extrathymic T cell selection. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001040462.3

Inheritance

—

ClinVar variants

U:71B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr5:180,899,077-180,950,906

External References & Databases

Ensembl (ENSG00000113303)

Transcript & Mutation Effects

hg38 • Region Span ~51.8 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 BTNL8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040462.3. 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	4 clinvar		5
missense			67 clinvar	8 clinvar		75
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	71	12	0	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040462.3	RefSeq	NP_001035552.1	8	MANE Select
ENST00000340184.9	Ensembl	ENSP00000342197.4	8	MANE Select
NM_001159707.2	RefSeq	NP_001153179.1	7	Standard
NM_001159708.2	RefSeq	NP_001153180.1	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

adaptive immune response
regulation of immune response
T cell receptor signaling pathway

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: ENST00000340184
Coding exons: 8
Length: 51830
Individuals with no LoFs: 125638
Homozygous LoFs: 16
Heterozygous LoFs: 94
Defined: 125748
p: 0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0922	284	280	1.02	0.0000160	3256
Missense (PolyPhen)		72	67.553	1.0658		892
Synonymous	0.606	105	113	0.928	0.00000699	980
Loss of Function	1.44	10	16.2	0.616	7.85e-7	177

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0039	0.0039	notable
Latino/Admixed American	0.00046	0.00029	rare
Ashkenazi Jewish	0.0010	0.00060	notable
East Asian	0.000058	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00021	rare
South Asian	0.00030	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May stimulate primary immune response. Acts on T-cell stimulated sub-optimally through the TCR/CD3 complex stimulating their proliferation and cytokine production. {ECO:0000269|PubMed:24036152}.;

Intolerance Scores

LoFtool: 0.941
RVIS EVS: 2.51
RVIS percentile EVS: 98.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00316

Gene Damage Prediction

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