KLHL26

protein-coding

kelch like family member 26, 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. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_018316.3

Inheritance

—

ClinVar variants

U:103B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr19:18,637,025-18,671,721

External References & Databases

Ensembl (ENSG00000167487)

Transcript & Mutation Effects

hg38 • Region Span ~34.7 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 KLHL26 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018316.3. 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	4 clinvar		5
missense			101 clinvar	2 clinvar		103
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	103	6	0	109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018316.3	RefSeq	NP_060786.1	3	MANE Select
ENST00000300976.9	Ensembl	ENSP00000300976.3	3	MANE Select
NM_001345981.2	RefSeq	NP_001332910.1	3	Standard
NM_001345982.2	RefSeq	NP_001332911.1	3	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300976
Coding exons: 3
Length: 33535
Individuals with no LoFs: 125414
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125474
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.31	373	452	0.826	0.0000348	3933
Missense (PolyPhen)		134	177.18	0.75631		1579
Synonymous	-0.780	233	218	1.07	0.0000188	1305
Loss of Function	1.64	12	19.9	0.603	0.00000101	196

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00043	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00066	0.00060	rare
Finnish	0.000057	0.000046	rare
European (Non-Finnish)	0.00022	0.00020	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.523
RVIS EVS: -1.64
RVIS percentile EVS: 2.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.285

Gene Damage Prediction

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