KBTBD12

protein-coding

kelch repeat and BTB domain containing 12, the group of BTB domain containing

Gene summary

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KLHDC6

MANE transcript

NM_207335.4

Inheritance

—

ClinVar variants

U:110B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr3:127,915,232-127,987,671

External References & Databases

Ensembl (ENSG00000187715)

Transcript & Mutation Effects

hg38 • Region Span ~72.4 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 KBTBD12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207335.4. 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
missense			108 clinvar	2 clinvar		110
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	110	2	0	112

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207335.4	RefSeq	NP_997218.2	5	MANE Select
ENST00000405109.5	Ensembl	ENSP00000385957.1	5	MANE Select
NM_001370224.1	RefSeq	NP_001357153.1	5	Standard
ENST00000343941.4	Ensembl	ENSP00000345478.4	4	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000405109
Coding exons: 5
Length: 72440
Individuals with no LoFs: 125325
Homozygous LoFs: 1
Heterozygous LoFs: 267
Defined: 125593
p: 0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.277	316	330	0.957	0.0000162	4106
Missense (PolyPhen)		120	129.7	0.92521		1550
Synonymous	1.01	103	117	0.881	0.00000566	1155
Loss of Function	0.618	23	26.4	0.870	0.00000153	322

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0048	0.0047	notable
Latino/Admixed American	0.0010	0.00098	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0034	0.0033	notable
Finnish	0.00048	0.00046	rare
European (Non-Finnish)	0.00049	0.00048	rare
South Asian	0.00098	0.00088	rare
Other	0.00084	0.00082	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0921

Intolerance Scores

LoFtool: 0.723
RVIS EVS: -0.11
RVIS percentile EVS: 45.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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