KLHL5

protein-coding

kelch like family member 5, 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. Located in microtubule cytoskeleton. Implicated in cocaine dependence. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015990.5

Inheritance

—

ClinVar variants

U:96B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr4:39,045,039-39,126,857

External References & Databases

Ensembl (ENSG00000109790)

Transcript & Mutation Effects

hg38 • Region Span ~81.8 kb

Loading mutation effect viewer...

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 KLHL5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015990.5. 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			1 clinvar	1 clinvar		2
missense			90 clinvar			90
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	96	1	0	97

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015990.5	RefSeq	NP_057074.4	11	MANE Select
ENST00000504108.7	Ensembl	ENSP00000423897.2	11	MANE Select
NM_001007075.2	RefSeq	NP_001007076.1	11	Standard
NM_001171654.1	RefSeq	NP_001165125.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

biological_process
post-translational protein modification

Molecular Function

molecular_function
actin binding

Cellular Component

cytoplasm
cytosol
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000504108
Coding exons: 11
Length: 81819
Individuals with no LoFs: 125659
Homozygous LoFs: 0
Heterozygous LoFs: 89
Defined: 125748
p: 0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	301	412	0.731	0.0000207	4943
Missense (PolyPhen)		102	172.4	0.59164		2026
Synonymous	0.337	141	146	0.965	0.00000741	1459
Loss of Function	3.15	15	35.2	0.426	0.00000176	429

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00052	0.00052	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.866
RVIS EVS: -0.16
RVIS percentile EVS: 42.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.511

Gene Damage Prediction

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