KLHL23

protein-coding

kelch like family member 23, the group of Kelch like|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, Jun 2026]

MANE transcript

NM_144711.6

Inheritance

—

ClinVar variants

U:62B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr2:169,694,488-169,776,989

External References & Databases

Ensembl (ENSG00000213160)

Transcript & Mutation Effects

hg38 • Region Span ~82.5 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 KLHL23 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144711.6. 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			62 clinvar	1 clinvar	1 clinvar	64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	1	1	64

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144711.6	RefSeq	NP_653312.2	3	MANE Select
ENST00000392647.7	Ensembl	ENSP00000376419.2	3	MANE Select
ENST00000272797.8	Ensembl	ENSP00000272797.4	3	Standard
ENST00000272797.9	Ensembl	ENSP00000272797.4	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392647
Coding exons: 3
Length: 82502
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125747
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.733	262	298	0.880	0.0000144	3688
Missense (PolyPhen)		70	111.64	0.62702		1370
Synonymous	0.143	106	108	0.982	0.00000575	1025
Loss of Function	2.79	8	22.2	0.361	0.00000116	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00028	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.647
RVIS EVS: -0.54
RVIS percentile EVS: 20.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.773

Gene Damage Prediction

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