CAND2

Summary

CAND2 (cullin associated and neddylation dissociated 2 (putative), HGNC:30689) is a protein-coding gene on chromosome 3p25.2, encoding Cullin-associated NEDD8-dissociated protein 2 (O75155). Probable 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.

Predicted to enable TBP-class protein binding activity. Predicted to be involved in SCF complex assembly; positive regulation of DNA-templated transcription; and protein ubiquitination. Located in cytosol.

Source: NCBI Gene 23066 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 27 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 273 total
• GTEx eGene: eQTL in 42 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.81 (unconstrained)
• MANE Select transcript: NM_001162499
• Notable: 273 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30689
Approved symbol	CAND2
Name	cullin associated and neddylation dissociated 2 (putative)
Location	3p25.2
Locus type	gene with protein product
Status	Approved
Aliases	TIP120B, KIAA0667, Tp120b
Ensembl gene	ENSG00000144712
Ensembl biotype	protein_coding
OMIM	610403
Entrez	23066

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000456430

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1, TSL 5: 1

ENST00000456430, ENST00000295989, ENST00000446928, ENST00000466558, ENST00000626378, ENST00000650119, ENST00000856238, ENST00000917140, ENST00000949513, ENST00000949514, ENST00000993545, ENST00001043112, ENST00001043113, ENST00001068300, ENST00001112913, ENST00001143639

RefSeq mRNA: 2 — MANE Select: NM_001162499 NM_001162499, NM_012298

CCDS: CCDS43053, CCDS54554

Canonical transcript exons

ENST00000456430 — 15 exons

Exon	Start	End
ENSE00000966686	12803488	12803631
ENSE00000966687	12810059	12810324
ENSE00000966688	12812990	12813095
ENSE00000966689	12813246	12813388
ENSE00000966690	12815141	12815433
ENSE00000966691	12815867	12816008
ENSE00000966692	12816374	12817876
ENSE00000966695	12827440	12827604
ENSE00001161869	12820086	12820181
ENSE00001619886	12807306	12807460
ENSE00001650494	12825470	12825639
ENSE00001723434	12796680	12796788
ENSE00001794332	12833755	12834803
ENSE00003515140	12808210	12808333
ENSE00004808367	12831465	12831572

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.13.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2475 / max 114.1299, expressed in 854 samples.

Highest expression (Bgee): skeletal muscle tissue of rectus abdominis, vastus lateralis, gluteal muscle, quadriceps femoris, skeletal muscle tissue of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CAND2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 42 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 46 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	2.2e-75	+0.59	3:12796794:G:C
Thyroid	eqtl	5.1e-44	-0.49	3:12801433:G:A
Cells Cultured fibroblasts	eqtl	1.7e-38	+1.01	3:12796685:C:T
Pituitary	eqtl	3.8e-25	-1.72	3:12796680:A:G
Artery Aorta	eqtl	1.0e-22	-1.59	3:12796680:A:G
Nerve Tibial	eqtl	6.1e-22	-1.59	3:12796680:A:G
Esophagus Muscularis	eqtl	2.6e-19	-1.40	3:12796680:A:G
Brain Cerebellar Hemisphere	eqtl	3.9e-18	-2.37	3:12796680:A:G
Brain Caudate basal ganglia	eqtl	3.8e-16	-1.39	3:12796680:A:G
Skin Sun Exposed Lower leg	eqtl	5.8e-15	-1.09	3:12796680:A:G
Brain Nucleus accumbens basal ganglia	eqtl	5.0e-14	-1.34	3:12796680:A:G
Skin Not Sun Exposed Suprapubic	eqtl	7.4e-14	+0.41	3:12796583:C:T
Breast Mammary Tissue	eqtl	6.2e-13	-1.00	3:12796680:A:G
Brain Hippocampus	eqtl	9.0e-13	-1.37	3:12796680:A:G
Brain Frontal Cortex BA9	eqtl	2.4e-12	-1.03	3:12796680:A:G
Adipose Subcutaneous	eqtl	2.5e-12	-0.80	3:12796680:A:G
Brain Cerebellum	eqtl	1.0e-11	-2.23	3:12796680:A:G
Lung	eqtl	1.3e-11	-1.33	3:12796680:A:G
Testis	sqtl	1.6e-11	+0.48	3:12881217:A:T
Esophagus Mucosa	eqtl	2.2e-10	-0.22	3:12762561:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
35393	4.0083	835
35392	0.2392	138

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.13	gold quality
vastus lateralis	UBERON:0001379	98.60	gold quality
gluteal muscle	UBERON:0002000	98.53	gold quality
quadriceps femoris	UBERON:0001377	98.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.19	gold quality
biceps brachii	UBERON:0001507	98.06	gold quality
triceps brachii	UBERON:0001509	97.94	gold quality
skeletal muscle tissue	UBERON:0001134	97.55	gold quality
sperm	CL:0000019	96.84	gold quality
deltoid	UBERON:0001476	96.79	gold quality
gastrocnemius	UBERON:0001388	96.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.31	gold quality
muscle organ	UBERON:0001630	96.12	gold quality
body of tongue	UBERON:0011876	96.02	gold quality
male germ cell	CL:0000015	95.69	gold quality
left ventricle myocardium	UBERON:0006566	95.69	gold quality
diaphragm	UBERON:0001103	95.41	gold quality
endothelial cell	CL:0000115	95.40	gold quality
muscle of leg	UBERON:0001383	95.34	gold quality
tibialis anterior	UBERON:0001385	95.07	gold quality
middle temporal gyrus	UBERON:0002771	94.82	gold quality
muscle tissue	UBERON:0002385	94.80	gold quality
heart right ventricle	UBERON:0002080	94.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.11	gold quality
myocardium	UBERON:0002349	93.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.12	gold quality
apex of heart	UBERON:0002098	91.62	gold quality
adult organism	UBERON:0007023	90.02	gold quality
oocyte	CL:0000023	90.01	gold quality
cardiac ventricle	UBERON:0002082	89.53	gold quality
heart left ventricle	UBERON:0002084	89.37	gold quality
blood vessel layer	UBERON:0004797	88.98	gold quality
secondary oocyte	CL:0000655	88.89	gold quality
renal glomerulus	UBERON:0000074	88.81	gold quality
tongue	UBERON:0001723	88.61	gold quality
choroid plexus epithelium	UBERON:0003911	88.39	gold quality
metanephric glomerulus	UBERON:0004736	87.83	gold quality
heart	UBERON:0000948	87.09	gold quality
cardiac atrium	UBERON:0002081	86.71	gold quality
primary visual cortex	UBERON:0002436	86.30	gold quality
right atrium auricular region	UBERON:0006631	86.06	gold quality
vena cava	UBERON:0004087	85.54	gold quality
entorhinal cortex	UBERON:0002728	85.36	gold quality
right testis	UBERON:0004534	85.21	gold quality
orbitofrontal cortex	UBERON:0004167	85.12	gold quality
testis	UBERON:0000473	85.07	gold quality
CA1 field of hippocampus	UBERON:0003881	84.72	silver quality
left testis	UBERON:0004533	84.68	gold quality
pigmented layer of retina	UBERON:0001782	84.59	gold quality
occipital lobe	UBERON:0002021	84.58	gold quality
retina	UBERON:0000966	84.57	gold quality
germinal epithelium of ovary	UBERON:0001304	84.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.36	gold quality
saphenous vein	UBERON:0007318	84.32	gold quality
parietal pleura	UBERON:0002400	84.26	gold quality
medial globus pallidus	UBERON:0002477	83.38	gold quality
mucosa of stomach	UBERON:0001199	83.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	83.27	gold quality
superior frontal gyrus	UBERON:0002661	83.22	gold quality
superior surface of tongue	UBERON:0007371	83.15	gold quality
pleura	UBERON:0000977	83.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.70	gold quality
visceral pleura	UBERON:0002401	82.54	gold quality
globus pallidus	UBERON:0001875	82.37	gold quality
tibia	UBERON:0000979	82.29	gold quality
prefrontal cortex	UBERON:0000451	82.16	gold quality
parietal lobe	UBERON:0001872	81.96	gold quality
postcentral gyrus	UBERON:0002581	81.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.73	gold quality
frontal cortex	UBERON:0001870	81.32	gold quality
trigeminal ganglion	UBERON:0001675	81.24	gold quality
buccal mucosa cell	CL:0002336	81.20	gold quality
popliteal artery	UBERON:0002250	81.07	gold quality
tibial artery	UBERON:0007610	81.04	gold quality
inferior olivary complex	UBERON:0002127	80.92	silver quality
neocortex	UBERON:0001950	80.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	80.46	silver quality
substantia nigra pars compacta	UBERON:0001965	80.31	silver quality
pharyngeal mucosa	UBERON:0000355	80.27	gold quality
cerebral cortex	UBERON:0000956	80.27	gold quality
medulla oblongata	UBERON:0001896	80.22	silver quality
Brodmann (1909) area 9	UBERON:0013540	80.20	gold quality
cranial nerve II	UBERON:0000941	80.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.09	gold quality
Brodmann (1909) area 10	UBERON:0013541	80.09	gold quality
ventral tegmental area	UBERON:0002691	80.04	gold quality
dorsal root ganglion	UBERON:0000044	79.91	gold quality
aorta	UBERON:0000947	79.91	gold quality
superior vestibular nucleus	UBERON:0007227	79.82	gold quality
tendon of biceps brachii	UBERON:0008188	79.58	silver quality
seminal vesicle	UBERON:0000998	79.45	gold quality
eye	UBERON:0000970	79.40	gold quality
right frontal lobe	UBERON:0002810	79.37	gold quality
temporal lobe	UBERON:0001871	79.33	gold quality
pons	UBERON:0000988	79.32	gold quality
stromal cell of endometrium	CL:0002255	79.17	gold quality
lateral globus pallidus	UBERON:0002476	79.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.91	gold quality
right coronary artery	UBERON:0001625	78.76	gold quality
pituitary gland	UBERON:0000007	78.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.27
E-MTAB-9543	no	1.22

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	109.4	medium
Tongue	tissue	33.7
Heart muscle	tissue	22.3	low
Cerebral cortex	tissue	17.7	not detected
Somatosensory cortex	tissue	17.7
Occipital cortex	tissue	16.4
Hippocampal formation	tissue	15.9
Entorhinal cortex	tissue	15.9
Temporal cortex	tissue	15.4
Insular cortex	tissue	15.3
Cerebellum	tissue	15.1	not detected
Retrosplenial and cingulate cortex	tissue	15.1
Prefrontal cortex	tissue	14.7
Motor cortex	tissue	14.6
Basal ganglia	tissue	14.3	not detected
Amygdala	tissue	13.7
Retrosplenial cortex	tissue	13.5
Superior colliculi	tissue	13.2
Olfactory bulb	tissue	12.8
Putamen	tissue	12.5
Thalamus	tissue	12.4
Ventral forebrain	tissue	12.4
Septum	tissue	12.3
Midbrain	tissue	11.6
Pons	tissue	11.1
Hypothalamus	tissue	11.1
Locus coeruleus	tissue	10.4
Medulla oblongata	tissue	9.6
Choroid plexus	tissue	9.5
Nucleus accumbens	tissue	9.3
Substantia nigra	tissue	8.8
Testis	tissue	8.4	low
Periaqueductal gray	tissue	8.2
Pituitary gland	tissue	7.7
Spinal cord	tissue	7.7
Hippocampus	tissue	6.1	not detected
Postcentral gyrus	tissue	6.1
Corpus callosum	tissue	5.1
Parathyroid gland	tissue	4.7	not detected
Smooth muscle	tissue	3.1	not detected
Endometrium 1	tissue	2.6	not detected
Vagina	tissue	2.5	not detected
Seminal vesicle	tissue	2.5	not detected
Ovary	tissue	2.4	not detected
Fallopian tube	tissue	2.4	high
Prostate	tissue	2.2	not detected
Esophagus	tissue	2.1	not detected
Epididymis	tissue	2.0	not detected
Pancreas	tissue	1.9	not detected
Salivary gland	tissue	1.8	not detected
Cervix	tissue	1.6	not detected
Adipose tissue	tissue	1.6	not detected
Spleen	tissue	1.6	not detected
Retina	tissue	1.5
Gallbladder	tissue	1.5	not detected
Caudate putamen	tissue	1.5
Thyroid gland	tissue	1.4	not detected
Adrenal gland	tissue	1.4	not detected
Urinary bladder	tissue	1.3	not detected
Lung	tissue	1.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Subiculum (14.4), Arcuate nucleus (14.0), Ventral hippocampus (13.7), Dorsal hippocampus (12.9), Habenula (12.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYOD1

miRNA regulators (miRDB)

Targeting CAND2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

25 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-3622B-5P	94.62	64.58	835

Functional genomics

gnomAD constraint: pLI 3.2e-13, LOEUF 0.815, missense Z 1.1 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000456430 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:12,796,721–12,803,591	62 / 77.3	0.80	no
3:12,803,592–12,807,349	12 / 32.6	0.37	no
3:12,807,350–12,833,979	1427 / 1545.3	0.92	no

Literature-anchored findings (GeneRIF, showing 7)

• TIP120B was induced in C2C12 myoblasts when these cells differentiated into myotubes (TIP120B). (PMID:12207886)
• TIP120B is a specific substrate of KIAA10; both are highly expressed in human skeletal muscle, suggesting that KIAA10 may regulate TIP120B homeostasis specifically in this tissue. (PMID:12692129)
• Based on these results it is unlikely CAND2 and WNT7a are the major genes that causes clubfoot. (PMID:19159115)
• results suggest that MyoD and TIP120B potentiate each other at gene expression and post-translation levels, respectively, which may promote myogenesis cooperatively (PMID:22613845)
• NEURL rs12415501 and CAND2 rs4642101 are significantly associated with postoperative atrial fibrillation susceptibility after coronary artery bypass grafting among Chinese population (PMID:27203392)
• The work developed the tool and performed “interaction analyses within chromatin regulatory circuitry” (IACRC); analysis found CAND2 may be a novel obesity susceptibility gene. (PMID:29717274)
• Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling. (PMID:34605609)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cand2	ENSDARG00000005749
mus_musculus	Cand2	ENSMUSG00000030319
rattus_norvegicus	Cand2	ENSRNOG00000010473
drosophila_melanogaster	Cand1	FBGN0027568
caenorhabditis_elegans		WBGENE00013606

Paralogs (1): CAND1 (ENSG00000111530)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914338) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased lean body mass	1
decreased circulating iron level	1
decreased response of heart to induced stress	1
decreased circulating thyroxine level	1
decreased total body fat amount	1
increased red blood cell distribution width	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A7MBJ5	100.0%	Diamond
Pongo abelii	Q5R6L5	98.5%	Diamond
Arabidopsis thaliana	Q8L5Y6	43.4%	Diamond
Dictyostelium discoideum	Q86KD1	41.1%	Diamond
Aspergillus nidulans FGSC A4	Q5BAH2	31.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RPL32	protein-coding	6161
SNORA7A	snoRNA	619563
LINC02022	ncRNA	105376955
IQSEC1	protein-coding	9922
TMEM40	protein-coding	55287
RAF1	protein-coding	5894

Protein

Protein identifiers

Cullin-associated NEDD8-dissociated protein 2 — O75155 (reviewed: O75155)

Alternative names: Cullin-associated and neddylation-dissociated protein 2, Epididymis tissue protein Li 169, TBP-interacting protein of 120 kDa B, p120 CAND2

All UniProt accessions (3): A0A3B3ISC4, O75155, F8WBB8

UniProt curated annotations — full annotation on UniProt →

Function. Probable 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.

Subunit / interactions. Binds TBP, CNOT3 and UBE3C.

Subcellular location. Nucleus.

Tissue specificity. Expressed in epididymis (at protein level).

Post-translational modifications. Ubiquitinated and targeted for proteasomal degradation.

Similarity. Belongs to the CAND family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75155-1	1	yes
O75155-2	2

RefSeq proteins (2): NP_001155971, NP_036430 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR013932	TATA-bd_TIP120	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039852	CAND1/CAND2	Family

Pfam: PF08623, PF13513, PF25782

UniProt features (139 total): helix 77, repeat 26, turn 10, strand 9, sequence variant 8, splice variant 3, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8VVY	Human Cullin-1 in complex with CAND2	ELECTRON MICROSCOPY	3.49
9PVH	Human Cullin-4 in complex with CAND2	ELECTRON MICROSCOPY	4.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75155-F1	87.14	0.57

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies; cytosol

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
N-acetylserine	2

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 101 (showing top): BROWNE_HCMV_INFECTION_14HR_DN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, CERVERA_SDHB_TARGETS_1_UP, MULLIGHAN_MLL_SIGNATURE_1_UP, GOMF_TRANSCRIPTION_FACTOR_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_TBP_CLASS_PROTEIN_BINDING, WONG_ADULT_TISSUE_STEM_MODULE, MARTENS_TRETINOIN_RESPONSE_DN, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_UP, CHICAS_RB1_TARGETS_CONFLUENT, LEE_BMP2_TARGETS_DN, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP, PLASARI_TGFB1_TARGETS_10HR_DN, PEDRIOLI_MIR31_TARGETS_DN

GO Biological Process (4): DNA-templated transcription (GO:0006351), SCF complex assembly (GO:0010265), protein ubiquitination (GO:0016567), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): TBP-class protein binding (GO:0017025), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytosol (GO:0005829)

GO top-level categories

12 GO namespaces:

Category	Terms
gene expression	1
RNA biosynthetic process	1
protein-containing complex assembly	1
protein modification by small protein conjugation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
general transcription initiation factor binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay

Protein interactions and networks

STRING

showing 16 of 719 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAND2	NEURL1	O76050	622
CAND2	TBP	P20226	607
CAND2	SYNPO2L	Q9H987	533
CAND2	NEDD8	Q15843	441
CAND2	AOPEP	Q8N6M6	429
CAND2	CUX2	O14529	428
CAND2	TMEM116	Q8NCL8	395
CAND2	KLHL25	Q9H0H3	383
CAND2	CUL1	Q13616	377
CAND2	KLHL12	Q53G59	366
CAND2	USP25	Q9UHP3	365
CAND2	ZFHX3	Q15911	365
CAND2	SKP1	P34991	364
CAND2	USP19	O94966	362
CAND2	TBX5	Q99593	352
CAND2	CUL5	Q93034	352

IntAct

Human interaction partners of CAND2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
CIDEB	physical association	0.560	3
FHL2	physical association	0.560	3
SYP	physical association	0.560	3
GLP1R	physical association	0.510	2
ALDH3A2	association	0.350	1
CD244	association	0.350	1
CUL4B	association	0.350	1
GLMN	association	0.350	1
IFIT5	association	0.350	1
MFSD2A	association	0.350	1
SLAMF9	association	0.350	1
SLCO5A1	association	0.350	1
DNAJB6	physical association	0.000	1
STOM	physical association	0.000	1

BioGRID (142 interactions; top human partners by supporting records): CUL1 (Affinity Capture-MS; 4 records), ALDH3A2 (Affinity Capture-MS; 3 records), CD244 (Affinity Capture-MS; 3 records), CUL3 (Affinity Capture-MS; 3 records), EFNB2 (Affinity Capture-MS; 3 records), PTGER3 (Affinity Capture-MS; 3 records), SCN2B (Affinity Capture-MS; 3 records), TNFSF13B (Affinity Capture-MS; 3 records), ADORA3 (Affinity Capture-MS; 2 records), BSG (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-MS; 2 records), CHRM4 (Affinity Capture-MS; 2 records), CNOT3 (Two-hybrid; 2 records), EGFR (Affinity Capture-MS; 2 records), EPHA1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
CNOT3	unknown	CAND2	binding
UBE3C	“down-regulates quantity by destabilization”	CAND2	ubiquitination

Disease & clinical

Genetic variants

Variant evidence for CAND2: 273 ClinVar records (0 pathogenic / likely pathogenic); 27 GWAS associations.

ClinVar

273 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	232
Likely benign	14
Benign	5

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 1,511):

Position(s)	Effect	Δscore	Sites
3:12803486–12803487	acceptor_loss	1.0000	6
3:12803632–12803633	donor_loss	1.0000	5
3:12808208–12808209	acceptor_loss	1.0000	4
3:12808326	donor_gain	1.0000
3:12810325–12810326	donor_loss	1.0000	5
3:12812988–12812989	acceptor_loss	1.0000	3
3:12813244–12813245	acceptor_loss	1.0000	4
3:12813368	donor_gain	1.0000
3:12813389–12813390	donor_loss	1.0000	5
3:12815422	donor_gain	1.0000

AlphaMissense

2,403 missense substitutions predicted likely pathogenic (of 7,960 scored), across 727 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M25	9	0.993	1.000
M15	9	0.953	0.998
M1073	9	0.933	0.996
D21	8	0.998	0.999
D59	8	0.997	0.999
D19	8	0.995	0.998
D29	8	0.993	0.997
D346	8	0.990	0.997
F1076	8	0.989	1.000
D1081	8	0.987	0.997
D1120	8	0.986	0.997
D311	8	0.984	0.998
D584	8	0.963	0.975
D1123	8	0.951	0.987
D104	8	0.944	0.988
D343	8	0.940	0.987
N66	8	0.919	0.997
D156	8	0.903	0.988
D707	8	0.898	0.956
N313	8	0.897	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:610403 | disease phenotypes:

GWAS associations

27 associations:

Study	Trait	p-value
GCST006414_105	Atrial fibrillation	2e-24
GCST006061_162	Atrial fibrillation	5e-23
GCST006061_200	Atrial fibrillation	4e-22
GCST010796_586	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-13
GCST010796_588	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-13
GCST010796_589	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-13
GCST010796_587	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-12
GCST006014_6	Creatine kinase levels	8e-11
GCST010796_598	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-10
GCST010796_597	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-10
GCST010796_595	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-10
GCST010796_599	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-10
GCST010796_590	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_596	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST90020027_1119	Waist-hip index	3e-9
GCST010796_591	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-9
GCST010796_592	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-9
GCST010796_593	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-9
GCST005962_54	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	9e-9
GCST90020025_1702	Waist-to-hip ratio adjusted for BMI	1e-8
GCST004826_1	P wave duration	2e-8
GCST010796_594	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-8
GCST005956_65	Waist-to-hip ratio adjusted for BMI	1e-7
GCST010724_9	HOMA-B (corrected for HOMA-IR)	1e-7
GCST005958_3	Waist-to-hip ratio adjusted for BMI (age >50)	2e-6
GCST008161_68	Waist circumference adjusted for body mass index	3e-6
GCST005957_13	Waist-to-hip ratio adjusted for BMI (age <50)	9e-6

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0005094	P wave duration
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004534	creatine kinase measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004469	HOMA-B
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
bisphenol A	decreases methylation	1
sodium arsenite	affects methylation	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases methylation, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects expression	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Metals, Heavy	decreases methylation, increases abundance	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.