KLHL35

protein-coding

kelch like family member 35, 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]

MANE transcript

NM_001039548.3

Inheritance

—

ClinVar variants

U:147B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.44

Max pathogenic AF

—

Genomic locus

chr11:75,422,394-75,433,203

External References & Databases

Ensembl (ENSG00000149243)

Transcript & Mutation Effects

hg38 • Region Span ~10.8 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 KLHL35 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 149

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039548.3. 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				3 clinvar		3
missense			145 clinvar	6 clinvar		151
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	147	9	0	156

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039548.3	RefSeq	NP_001034637.2	6	MANE Select
ENST00000539798.3	Ensembl	ENSP00000438526.1	6	MANE Select
ENST00000376292.8	Ensembl	ENSP00000365469.4	6	Standard
ENST00000905843.1	Ensembl	ENSP00000575902.1	6	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: ENST00000539798
Coding exons: 6
Length: 8237
Individuals with no LoFs: 124563
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 124645
p: 0.000329

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.151	226	220	1.03	0.0000138	3570
Missense (PolyPhen)		7	5.7301	1.2216		321
Synonymous	0.721	88	97.0	0.907	0.00000648	1247
Loss of Function	-1.47	19	13.2	1.44	5.65e-7	189

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00040	0.00039	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00067	0.00067	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00036	0.00035	rare
South Asian	0.00030	0.00029	rare
Other	0.00083	0.00083	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.115

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.181

Gene Damage Prediction

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