KBTBD2

protein-coding

kelch repeat and BTB domain containing 2, the group of BTB domain containing

Gene summary

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in protein K48-linked ubiquitination and regulation of cellular response to insulin stimulus. Acts upstream of or within with a positive effect on protein polyubiquitination. Located in nucleus. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

BKLHD1

MANE transcript

NM_015483.3

Inheritance

ClinVar variants

U:43B:1

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr7:32,868,172-32,894,131

External References & Databases

Ensembl (ENSG00000170852)

Transcript & Mutation Effects

hg38 • Region Span ~26.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KBTBD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015483.3. 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	1 clinvar		2
missense			41 clinvar			41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	43	1	0	44

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015483.3	RefSeq	NP_056298.2	3	MANE Select
ENST00000304056.9	Ensembl	ENSP00000302586.4	3	MANE Select
ENST00000423022.1	Ensembl	ENSP00000407520.1	1	Standard
ENST00000424468.1	Ensembl	ENSP00000388236.1	1	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304056
Coding exons: 3
Length: 25960
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125699
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.69	194	332	0.585	0.0000172	4105
Missense (PolyPhen)		31	85.947	0.36069		1088
Synonymous	-0.128	122	120	1.01	0.00000627	1188
Loss of Function	4.45	2	26.9	0.0743	0.00000172	300

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.145
RVIS EVS: -0.67
RVIS percentile EVS: 15.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.861

Gene Damage Prediction

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