CAND1

protein-coding

cullin associated and neddylation dissociated 1, the group of Armadillo like helical domain containing

Gene summary

This gene encodes an essential regulator of Cullin-RING ubiquitin ligases, which are in involved in ubiquitinylation of proteins degraded by the Ub proteasome system. The encoded protein binds to unneddylated cullin-RING box protein complexes and acts as an inhibitor of cullin neddylation and of Skp1, cullin, and F box ubiquitin ligase complex assembly and activity. In mammalian cell culture, this protein predominantly localizes to the cytoplasm. Knockdown of this gene in preadipocytes results in blocked adipogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

MANE transcript

NM_018448.5

Inheritance

—

ClinVar variants

U:82

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr12:67,269,358-67,319,953

External References & Databases

Ensembl (ENSG00000111530)

Transcript & Mutation Effects

hg38 • Region Span ~50.6 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 CAND1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018448.5. 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			1 clinvar			1
missense			75 clinvar			75
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	82	0	0	82

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018448.5	RefSeq	NP_060918.2	15	MANE Select
ENST00000545606.6	Ensembl	ENSP00000442318.1	15	MANE Select
NM_001329674.2	RefSeq	NP_001316603.1	14	Standard
NM_001329675.2	RefSeq	NP_001316604.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cand1	Danio rerio	Structure: atrial cardiac muscle cell action potential Quality: increased duration abnormal

Gene / Model

Organism

Observed Phenotype

cand1

Danio rerio

Structure: atrial cardiac muscle cell action potential

Quality: increased duration

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Endoderm Differentiation
Neutrophil degranulation

Biological Process

cellular iron ion homeostasis
SCF complex assembly
protein ubiquitination
cell differentiation
negative regulation of catalytic activity

Molecular Function

protein binding
TBP-class protein binding

Cellular Component

ubiquitin ligase complex
extracellular region
nucleus
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000545606
Coding exons: 15
Length: 50671
Individuals with no LoFs: 125466
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125467
p: 0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.16	338	632	0.535	0.0000307	8047
Missense (PolyPhen)		58	209.46	0.2769		2808
Synonymous	-0.268	233	228	1.02	0.0000113	2422
Loss of Function	6.22	1	47.1	0.0212	0.00000241	655

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
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: Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes. {ECO:0000269|PubMed:12504025, ECO:0000269|PubMed:12504026, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:16449638, ECO:0000269|PubMed:21249194, ECO:0000269|PubMed:23453757}.;

Recessive Scores

pRec: 0.171

Intolerance Scores

LoFtool: 0.0165
RVIS EVS: -1.04
RVIS percentile EVS: 7.71

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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