CUL9

protein-coding

cullin 9, the group of Armadillo like helical domain containing|RBR E3 ubiquitin ligases|Cullins

Gene summary

Predicted to enable ubiquitin ligase complex scaffold activity. Involved in microtubule cytoskeleton organization; protein ubiquitination; and regulation of mitotic nuclear division. Part of cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015089.4

Inheritance

—

ClinVar variants

U:368B:62

Top phenotype

CUL9-related disorder

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr6:43,182,184-43,224,587

External References & Databases

Ensembl (ENSG00000112659)

Transcript & Mutation Effects

hg38 • Region Span ~42.4 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 CUL9 variants in ClinVar

18 Conditions Cataloged

not specifiedTotal: 351

CUL9-related disorderTotal: 51

not providedTotal: 19

Psoriasiform dermatitisTotal: 2

Absent/hypoplastic coccyxTotal: 2

Moderate intellectual disabilityTotal: 2

Delayed skeletal maturationTotal: 2

Ventricular septal defectTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015089.4. 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			8 clinvar	17 clinvar	8 clinvar	33
missense			344 clinvar	31 clinvar	5 clinvar	380
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			11 clinvar	1 clinvar		12
Total	0	0	368	49	13	430

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015089.4	RefSeq	NP_055904.1	40	MANE Select
ENST00000252050.9	Ensembl	ENSP00000252050.4	40	MANE Select
ENST00000372647.6	Ensembl	ENSP00000361730.2	40	Standard
ENST00000372647.7	Ensembl	ENSP00000361730.2	40	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Neddylation

Biological Process

microtubule cytoskeleton organization
ubiquitin-dependent protein catabolic process
regulation of mitotic nuclear division
protein ubiquitination
post-translational protein modification

Molecular Function

protein binding
ATP binding
transferase activity
ubiquitin protein ligase binding
metal ion binding

Cellular Component

cytosol
cullin-RING ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252050
Coding exons: 40
Length: 42413
Individuals with no LoFs: 124966
Homozygous LoFs: 5
Heterozygous LoFs: 777
Defined: 125748
p: 0.00311

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.10	1154	1.49e+3	0.774	0.0000929	16322
Missense (PolyPhen)		421	635.21	0.66277		7260
Synonymous	0.423	589	602	0.978	0.0000366	5161
Loss of Function	8.27	25	125	0.201	0.00000679	1314

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.0018	0.0018	notable
East Asian	0.00016	0.00016	rare
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.0043	0.0043	notable
South Asian	0.0057	0.0056	notable
Other	0.0034	0.0034	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Core component of a Cul9-RING ubiquitin-protein ligase complex, a complex that mediates ubiquitination and subsequent degradation of BIRC5 and is required to maintain microtubule dynamics and genome integrity. Acts downstream of the 3M complex, which inhibits CUL9 activity, leading to prevent ubiquitination of BIRC5 (PubMed:24793696). Cytoplasmic anchor protein in p53/TP53- associated protein complex. Regulates the subcellular localization of p53/TP53 and subsequent function (PubMed:12526791, PubMed:17332328). {ECO:0000269|PubMed:12526791, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:24793696}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.536
RVIS EVS: -2.21
RVIS percentile EVS: 1.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.840

Gene Damage Prediction

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