KBTBD8

protein-coding

kelch repeat and BTB domain containing 8, the group of BTB domain containing

Gene summary

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in neural crest cell development; neural crest formation; and protein monoubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032505.3

Inheritance

—

ClinVar variants

U:67

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr3:66,998,307-67,011,210

External References & Databases

Ensembl (ENSG00000163376)

Transcript & Mutation Effects

hg38 • Region Span ~12.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KBTBD8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 67

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032505.3. 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						0
missense			67 clinvar			67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	0	0	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032505.3	RefSeq	NP_115894.2	4	MANE Select
ENST00000417314.2	Ensembl	ENSP00000401878.2	4	MANE Select
ENST00000460576.5	Ensembl	ENSP00000419738.1	2	Standard
ENST00000460576.6	Ensembl	ENSP00000419738.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

regulation of translation
protein monoubiquitination
neural crest formation
neural crest cell development
post-translational protein modification

Molecular Function

protein binding

Cellular Component

Golgi apparatus
spindle
cytosol
Cul3-RING ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417314
Coding exons: 4
Length: 12908
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125748
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	258	321	0.803	0.0000166	4003
Missense (PolyPhen)		64	102.4	0.62502		1234
Synonymous	0.295	106	110	0.964	0.00000575	1110
Loss of Function	2.21	12	23.6	0.509	0.00000138	285

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification (PubMed:26399832). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1: monoubiquitination promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:26399832}.;

Recessive Scores

pRec: 0.0996

Intolerance Scores

LoFtool: 0.633
RVIS EVS: 0.06
RVIS percentile EVS: 58.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.194

Gene Damage Prediction

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