KLHL21

protein-coding

kelch like family member 21, the group of Kelch like|BTB domain containing

Gene summary

Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in centrosome and polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014851.4

Inheritance

—

ClinVar variants

U:103B:13

Top phenotype

KLHL21-related disorder

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr1:6,590,724-6,614,607

External References & Databases

Ensembl (ENSG00000162413)

Transcript & Mutation Effects

hg38 • Region Span ~23.9 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 KLHL21 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 104

KLHL21-related disorderTotal: 10

EpendymomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014851.4. 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	6 clinvar	2 clinvar	9
missense			102 clinvar	4 clinvar	1 clinvar	107
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	103	10	3	116

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014851.4	RefSeq	NP_055666.2	4	MANE Select
ENST00000377658.8	Ensembl	ENSP00000366886.4	4	MANE Select
NM_001324309.2	RefSeq	NP_001311238.1	4	Standard
ENST00000377663.3	Ensembl	ENSP00000366891.3	3	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

cell cycle
protein ubiquitination
regulation of cytokinesis
chromosome passenger complex localization to spindle midzone
post-translational protein modification

Molecular Function

ubiquitin-protein transferase activity

Cellular Component

polar microtubule
cytosol
Cul3-RING ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377658
Coding exons: 4
Length: 23884
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125719
p: 0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.49	266	344	0.774	0.0000206	3755
Missense (PolyPhen)		52	97.464	0.53353		1123
Synonymous	-3.57	218	160	1.36	0.0000106	1264
Loss of Function	1.17	12	17.2	0.696	7.46e-7	187

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000084	0.000079	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:19995937}.;

Recessive Scores

pRec: 0.117

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.887

Gene Damage Prediction

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