KLHL28

protein-coding

kelch like family member 28, the group of BTB domain containing|Kelch like

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:

BTBD5

MANE transcript

NM_017658.5

Inheritance

—

ClinVar variants

U:54B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr14:44,924,324-45,042,322

External References & Databases

Ensembl (ENSG00000179454)

Transcript & Mutation Effects

hg38 • Region Span ~118.0 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 KLHL28 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 51

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017658.5. 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			52 clinvar	2 clinvar		54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	54	2	0	56

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017658.5	RefSeq	NP_060128.2	4	MANE Select
ENST00000396128.9	Ensembl	ENSP00000379434.4	4	MANE Select
NM_001308112.2	RefSeq	NP_001295041.1	5	Standard
ENST00000355081.3	Ensembl	ENSP00000347193.2	5	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396128
Coding exons: 4
Length: 118004
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125735
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.20	212	323	0.655	0.0000171	3749
Missense (PolyPhen)		54	103.87	0.51986		1184
Synonymous	-0.522	121	114	1.06	0.00000617	1122
Loss of Function	3.03	7	22.5	0.311	0.00000130	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.200
RVIS EVS: 0.2
RVIS percentile EVS: 67.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.827

Gene Damage Prediction

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