KLHL18

protein-coding

kelch like family member 18, the group of BTB domain containing|Kelch like

Gene summary

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in positive regulation of mitotic cell cycle phase transition and protein ubiquitination. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_025010.5

Inheritance

—

ClinVar variants

U:75B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr3:47,282,917-47,346,816

External References & Databases

Ensembl (ENSG00000114648)

Transcript & Mutation Effects

hg38 • Region Span ~63.9 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 KLHL18 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 72

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025010.5. 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			72 clinvar	1 clinvar		73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	75	1	0	76

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025010.5	RefSeq	NP_079286.2	10	MANE Select
ENST00000232766.6	Ensembl	ENSP00000232766.5	10	MANE Select
ENST00000433449.5	Ensembl	ENSP00000407114.1	2	Standard
ENST00000437353.5	Ensembl	ENSP00000411839.2	4	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: ENST00000232766
Coding exons: 10
Length: 63900
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.01	263	372	0.707	0.0000229	3764
Missense (PolyPhen)		101	144.31	0.69986		1362
Synonymous	0.788	136	148	0.918	0.00000966	1141
Loss of Function	3.43	7	25.8	0.271	0.00000116	292

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.109

Intolerance Scores

RVIS EVS: -0.89
RVIS percentile EVS: 10.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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