CACUL1

protein-coding

CDK2 associated cullin domain 1

Gene summary

Enables protein kinase binding activity. Involved in G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C10orf46

MANE transcript

NM_153810.5

Inheritance

—

ClinVar variants

P:1U:49B:2

Top phenotype

Flexion contracture

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr10:118,674,167-118,755,249

External References & Databases

Ensembl (ENSG00000151893)

Transcript & Mutation Effects

hg38 • Region Span ~81.1 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 CACUL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 5

Flexion contractureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153810.5. 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				2 clinvar		2
missense			43 clinvar			43
nonsense			3 clinvar			3
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	49	2	0	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153810.5	RefSeq	NP_722517.3	9	MANE Select
ENST00000369151.8	Ensembl	ENSP00000358147.2	9	MANE Select
ENST00000493518.5	Ensembl	ENSP00000431329.1	7	Standard
ENST00000911131.1	Ensembl	ENSP00000581190.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

G1/S transition of mitotic cell cycle
ubiquitin-dependent protein catabolic process
positive regulation of cell population proliferation
positive regulation of protein kinase activity

Molecular Function

protein binding
protein kinase binding
ubiquitin protein ligase binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369151
Coding exons: 9
Length: 81083
Individuals with no LoFs: 124788
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124793
p: 0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.651	175	201	0.871	0.00000941	2423
Missense (PolyPhen)		24	44.42	0.5403		588
Synonymous	-0.610	83	76.2	1.09	0.00000392	685
Loss of Function	3.63	2	19.1	0.105	9.04e-7	234

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000072	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000049	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000037	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell cycle associated protein capable of promoting cell proliferation through the activation of CDK2 at the G1/S phase transition. {ECO:0000269|PubMed:19829063}.;

Intolerance Scores

RVIS EVS: -0.63
RVIS percentile EVS: 17.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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