KLHL9

protein-coding

kelch like family member 9, the group of BTB domain containing|Kelch like

Gene summary

This gene encodes a protein that belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain, a BACK domain and six C-terminal kelch repeats. The encoded protein is a component of a complex with cullin 3-based E3 ligase, which plays a role in mitosis. This protein complex is a cell cycle regulator, and functions in the organization and integrity of the spindle midzone in anaphase and the completion of cytokinesis. The complex is required for the removal of the chromosomal passenger protein aurora B from mitotic chromosomes. [provided by RefSeq, Jul 2016]

MANE transcript

NM_018847.4

Inheritance

ClinVar variants

U:155B:50

Top phenotype

KLHL9-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr9:21,320,024-21,335,404

External References & Databases

Ensembl (ENSG00000198642)

Transcript & Mutation Effects

hg38 • Region Span ~15.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

distal myopathyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0018949

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLHL9 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 162

not specifiedTotal: 61

KLHL9-related disorderTotal: 6

KLHL9-related distal myopathyTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018847.4. 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			15 clinvar	42 clinvar	3 clinvar	60
missense			135 clinvar	3 clinvar	2 clinvar	140
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	0	0	155	45	5	205

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018847.4	RefSeq	NP_061335.1	1	MANE Select
ENST00000359039.5	Ensembl	ENSP00000351933.4	1	MANE Select
ENST00000718394.1	Ensembl	ENSP00000520799.1	1	Standard
ENST00000718395.1	Ensembl	ENSP00000520800.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System

Biological Process

cell cycle
protein ubiquitination
regulation of cytokinesis
post-translational protein modification
cell division

Molecular Function

ubiquitin-protein transferase activity

Cellular Component

cytosol
midbody
Cul3-RING ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359039
Coding exons: 1
Length: 5710
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.87	231	326	0.709	0.0000167	4090
Missense (PolyPhen)		50	115.6	0.43252		1472
Synonymous	-1.81	137	113	1.22	0.00000554	1188
Loss of Function	3.38	3	18.8	0.159	0.00000118	246

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	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:19995937}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.410
RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.866

Gene Damage Prediction

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