KLHL38

protein-coding

kelch like family member 38, 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_001081675.3

Inheritance

—

ClinVar variants

U:124B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr8:123,644,442-123,653,801

External References & Databases

Ensembl (ENSG00000175946)

Transcript & Mutation Effects

hg38 • Region Span ~9.4 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 KLHL38 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 126

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001081675.3. 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	2 clinvar	3
missense			123 clinvar	3 clinvar	1 clinvar	127
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	124	4	3	131

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001081675.3	RefSeq	NP_001075144.2	3	MANE Select
ENST00000684634.1	Ensembl	ENSP00000508228.1	3	MANE Select
ENST00000325995.7	Ensembl	ENSP00000321475.7	3	Standard
ENST00000325995.8	Ensembl	ENSP00000321475.7	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: ENST00000325995
Coding exons: 3
Length: 7424
Individuals with no LoFs: 124715
Homozygous LoFs: 1
Heterozygous LoFs: 96
Defined: 124812
p: 0.000389

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.23	412	348	1.19	0.0000206	3827
Missense (PolyPhen)		95	80.444	1.1809		820
Synonymous	-2.28	185	149	1.24	0.00000992	1139
Loss of Function	0.791	14	17.6	0.796	8.32e-7	214

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00045	0.00045	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00061	0.00061	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00049	0.00048	rare
South Asian	0.00069	0.00065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.442
RVIS EVS: 0.52
RVIS percentile EVS: 80.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.202

Gene Damage Prediction

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