COMMD3

Summary

COMMD3 (COMM domain containing 3, HGNC:23332) is a protein-coding gene on chromosome 10p12.2, encoding COMM domain-containing protein 3 (Q9UBI1). Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex.

Predicted to be involved in endocytic recycling. Predicted to act upstream of or within intracellular copper ion homeostasis. Part of protein-containing complex.

Source: NCBI Gene 23412 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 9 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.33 (unconstrained)
• MANE Select transcript: NM_012071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23332
Approved symbol	COMMD3
Name	COMM domain containing 3
Location	10p12.2
Locus type	gene with protein product
Status	Approved
Aliases	BUP
Ensembl gene	ENSG00000148444
Ensembl biotype	protein_coding
OMIM	616700
Entrez	23412

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 15 protein_coding, 10 nonsense_mediated_decay, 6 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000376836

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 5, TSL 3: 4, TSL 5: 4

ENST00000376836, ENST00000444869, ENST00000448361, ENST00000456711, ENST00000463688, ENST00000468179, ENST00000468469, ENST00000470045, ENST00000471350, ENST00000472610, ENST00000472673, ENST00000479958, ENST00000483684, ENST00000496071, ENST00000602574, ENST00000860458, ENST00000860459, ENST00000860460, ENST00000860461, ENST00000964928, ENST00000999519, ENST00000999520, ENST00000999521, ENST00001041057, ENST00001041058, ENST00001041060, ENST00001041061, ENST00001099960, ENST00001099961, ENST00001099962, ENST00001099963, ENST00001099964, ENST00001119572, ENST00001137339

RefSeq mRNA: 1 — MANE Select: NM_012071 NM_012071

CCDS: CCDS7137

Canonical transcript exons

ENST00000376836 — 8 exons

Exon	Start	End
ENSE00001822108	22316388	22316556
ENSE00003496732	22317884	22317995
ENSE00003555854	22318272	22318306
ENSE00003558432	22318806	22318862
ENSE00003611347	22318959	22319018
ENSE00003620155	22319939	22320306
ENSE00003620718	22318105	22318168
ENSE00003623512	22318653	22318713

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0299 / max 4.2606, expressed in 14 samples.

Highest expression (Bgee): diaphragm, body of pancreas, triceps brachii, parotid gland, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COMMD3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	2.7e-04	+0.30	10:22313171:C:G
Artery Tibial	eqtl	5.4e-03	-0.32	10:23067782:C:T
Esophagus Muscularis	eqtl	7.1e-03	+0.30	10:21876772:C:G
Pancreas	eqtl	8.1e-03	+0.37	10:22275669:G:A
Colon Transverse	sqtl	1.2e-02	-1.79	10:22348150:C:G
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-02	+0.14	10:22499231:C:T
Cells Cultured fibroblasts	eqtl	2.4e-02	+0.23	10:22319242:C:G
Brain Cerebellar Hemisphere	eqtl	2.9e-02	+0.55	10:22279215:C:T
Heart Atrial Appendage	eqtl	3.2e-02	+0.33	10:23142679:T:C
Vagina	eqtl	3.4e-02	+1.30	10:21650672:A:G
Testis	eqtl	3.8e-02	-0.33	10:22013510:T:C
Colon Sigmoid	eqtl	4.4e-02	+0.51	10:22281462:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
104230	62.2653	1826
104234	0.0299	14

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	97.92	gold quality
body of pancreas	UBERON:0001150	97.48	gold quality
triceps brachii	UBERON:0001509	97.13	gold quality
parotid gland	UBERON:0001831	97.08	gold quality
cortical plate	UBERON:0005343	97.02	gold quality
left ventricle myocardium	UBERON:0006566	96.92	gold quality
thymus	UBERON:0002370	96.64	gold quality
heart right ventricle	UBERON:0002080	96.58	gold quality
biceps brachii	UBERON:0001507	96.54	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.47	gold quality
monocyte	CL:0000576	96.46	gold quality
mononuclear cell	CL:0000842	96.43	gold quality
heart left ventricle	UBERON:0002084	96.41	gold quality
olfactory bulb	UBERON:0002264	96.41	silver quality
cardiac ventricle	UBERON:0002082	96.40	gold quality
right atrium auricular region	UBERON:0006631	96.37	gold quality
left testis	UBERON:0004533	96.36	gold quality
myocardium	UBERON:0002349	96.34	gold quality
cardiac atrium	UBERON:0002081	96.31	gold quality
adenohypophysis	UBERON:0002196	96.30	gold quality
vastus lateralis	UBERON:0001379	96.28	gold quality
leukocyte	CL:0000738	96.27	gold quality
right testis	UBERON:0004534	96.25	gold quality
quadriceps femoris	UBERON:0001377	96.22	gold quality
gluteal muscle	UBERON:0002000	96.19	gold quality
heart	UBERON:0000948	96.17	gold quality
superficial temporal artery	UBERON:0001614	96.10	gold quality
pituitary gland	UBERON:0000007	96.08	gold quality
pancreas	UBERON:0001264	96.07	gold quality
calcaneal tendon	UBERON:0003701	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.02	gold quality
cerebellar hemisphere	UBERON:0002245	95.96	gold quality
type B pancreatic cell	CL:0000169	95.95	gold quality
cerebellar cortex	UBERON:0002129	95.90	gold quality
saliva-secreting gland	UBERON:0001044	95.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.87	gold quality
tongue squamous epithelium	UBERON:0006919	95.80	gold quality
right uterine tube	UBERON:0001302	95.79	gold quality
islet of Langerhans	UBERON:0000006	95.77	gold quality
ganglionic eminence	UBERON:0004023	95.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.77	gold quality
trabecular bone tissue	UBERON:0002483	95.75	gold quality
testis	UBERON:0000473	95.74	gold quality
rectum	UBERON:0001052	95.74	gold quality
minor salivary gland	UBERON:0001830	95.63	gold quality
lymph node	UBERON:0000029	95.61	gold quality
smooth muscle tissue	UBERON:0001135	95.58	gold quality
muscle organ	UBERON:0001630	95.57	gold quality
hair follicle	UBERON:0002073	95.57	gold quality
skin of abdomen	UBERON:0001416	95.54	gold quality
deltoid	UBERON:0001476	95.48	gold quality
mouth mucosa	UBERON:0003729	95.48	gold quality
periodontal ligament	UBERON:0008266	95.45	gold quality
germinal epithelium of ovary	UBERON:0001304	95.43	gold quality
muscle of leg	UBERON:0001383	95.43	gold quality
spinal cord	UBERON:0002240	95.43	gold quality
cerebellum	UBERON:0002037	95.41	gold quality
gastrocnemius	UBERON:0001388	95.38	gold quality
muscle tissue	UBERON:0002385	95.37	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.37	gold quality
skeletal muscle tissue	UBERON:0001134	95.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.30	gold quality
male germ cell	CL:0000015	95.29	gold quality
gingival epithelium	UBERON:0001949	95.29	gold quality
spleen	UBERON:0002106	95.27	gold quality
lower esophagus	UBERON:0013473	95.27	gold quality
right adrenal gland cortex	UBERON:0035827	95.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.27	gold quality
right adrenal gland	UBERON:0001233	95.24	gold quality
epithelium of bronchus	UBERON:0002031	95.21	gold quality
descending thoracic aorta	UBERON:0002345	95.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.20	gold quality
cervix epithelium	UBERON:0004801	95.18	gold quality
skin of leg	UBERON:0001511	95.13	gold quality
gingiva	UBERON:0001828	95.13	gold quality
bronchus	UBERON:0002185	95.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.10	gold quality
apex of heart	UBERON:0002098	95.09	gold quality
cervix squamous epithelium	UBERON:0006922	95.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.08	gold quality
zone of skin	UBERON:0000014	95.08	gold quality
sperm	CL:0000019	95.07	gold quality
bone marrow	UBERON:0002371	95.06	gold quality
body of tongue	UBERON:0011876	95.06	gold quality
right coronary artery	UBERON:0001625	95.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.02	gold quality
left coronary artery	UBERON:0001626	95.00	gold quality
transverse colon	UBERON:0001157	94.99	gold quality
bronchial epithelial cell	CL:0002328	94.97	gold quality
gall bladder	UBERON:0002110	94.94	gold quality
ascending aorta	UBERON:0001496	94.92	gold quality
thoracic aorta	UBERON:0001515	94.92	gold quality
vermiform appendix	UBERON:0001154	94.90	gold quality
body of uterus	UBERON:0009853	94.85	gold quality
right lung	UBERON:0002167	94.83	gold quality
nucleus accumbens	UBERON:0001882	94.80	gold quality
large intestine	UBERON:0000059	94.79	gold quality
colon	UBERON:0001155	94.79	gold quality
left adrenal gland	UBERON:0001234	94.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	33.70
E-ANND-3	yes	19.51
E-GEOD-36552	no	39.91

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	100.0
Caudate putamen	tissue	92.9
Heart muscle	tissue	74.7	low
Corpus callosum	tissue	72.6
Tongue	tissue	71.0
Skeletal muscle	tissue	70.7	medium
Spinal cord	tissue	66.6
Substantia nigra	tissue	64.3
Medulla oblongata	tissue	62.8
Pons	tissue	62.4
Hippocampal formation	tissue	61.8
Superior colliculi	tissue	61.6
Midbrain	tissue	61.4
Thalamus	tissue	59.5
Liver	tissue	58.7	medium
Putamen	tissue	57.9
Cerebellum	tissue	57.9	low
Septum	tissue	57.2
Thymus	tissue	57.0
Hypothalamus	tissue	55.6
Olfactory bulb	tissue	54.7
Periaqueductal gray	tissue	53.1
Prefrontal cortex	tissue	50.3
Cerebral cortex	tissue	50.3	medium
Parathyroid gland	tissue	50.2	low
Ventral forebrain	tissue	50.2
Motor cortex	tissue	49.9
Breast	tissue	49.3	high
Somatosensory cortex	tissue	49.0
Occipital cortex	tissue	49.0
Salivary gland	tissue	48.8	high
Pancreas	tissue	48.7	high
Retrosplenial and cingulate cortex	tissue	47.1
Basal ganglia	tissue	46.9	medium
Entorhinal cortex	tissue	46.4
Temporal cortex	tissue	45.8
Epididymis	tissue	45.1	medium
Retrosplenial cortex	tissue	45.1
Insular cortex	tissue	44.0
Amygdala	tissue	43.6
Lymph node	tissue	42.4	low
Tonsil	tissue	40.7	medium
Urinary bladder	tissue	37.1	high
Smooth muscle	tissue	36.4	low
Ovary	tissue	36.3	medium
Appendix	tissue	36.1	medium
Kidney	tissue	36.0	high
Bone marrow	tissue	36.0	high
Esophagus	tissue	35.8	medium
Colon	tissue	35.8	medium
Duodenum	tissue	35.3	medium
Pituitary gland	tissue	35.1
Rectum	tissue	34.6	medium
Small intestine	tissue	34.6	medium
Skin 1	tissue	34.5	medium
Prostate	tissue	34.4	medium
Adrenal gland	tissue	33.3	medium
Fallopian tube	tissue	32.6	high
Stomach 1	tissue	31.1	medium
Thyroid gland	tissue	31.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (72.6), Ventral spinal cord (66.6), Dorsal spinal cord (66.0), Dorsal hippocampus (61.8), Ventral hippocampus (51.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COMMD3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

19 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-4790-3P	96.63	67.08	806

Functional genomics

gnomAD constraint: pLI 4.7e-11, LOEUF 1.33, missense Z -0.843 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000376836 — one region, missense o/e 1.16.

Literature-anchored findings (GeneRIF, showing 6)

• complex determines GRK6 specificity for chemoattractant receptors (PMID:31088898)
• Data show that COMMD3 level is elevated in prostate cancer cell models, PDX models, and metastases. A positive correlation between increased COMMD3 expression and disease recurrence and poor survival was found. COMMD3 drives proliferation of normal cells and promotes migration/invasiveness of neoplastic cells. COMMD3:BMI1 fusion protein and COMMD3 regulate C-MYC transcription and C-MYC downstream pathway. (PMID:31467179)
• Transcriptional analysis of the expression, prognostic value and immune infiltration activities of the COMMD protein family in hepatocellular carcinoma. (PMID:34493238)
• Syntaxin 12 and COMMD3 are new factors that function with VPS33B in the biogenesis of platelet alpha-granules. (PMID:34905616)
• COMMD3-Mediated Endosomal Trafficking of HER2 Inhibits the Progression of Ovarian Carcinoma. (PMID:36445330)
• COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis. (PMID:37072858)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	commd3	ENSDARG00000045402
mus_musculus	Commd3	ENSMUSG00000051154
rattus_norvegicus	Commd3	ENSRNOG00000016383
drosophila_melanogaster	CG12106	FBGN0030100

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88218) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased body length	1
decreased IgM level	1
increased lean body mass	1
decreased follicular B cell number	1
abnormal follicular B cell physiology	1
decreased mature B cell number	1
abnormal spleen B cell follicle morphology	1
decreased spleen germinal center number	1
decreased IgG1 level	1
decreased IgG2b level	1
decreased IgG2c level	1
increased total body fat amount	1
abnormal plasmablast number	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	Q3SZ76	91.8%	Diamond
Dictyostelium discoideum	Q54QK4	32.1%	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
TRN-GTT2-3	tRNA	100189083
COMMD3-BMI1	protein-coding	100532731
LINC03027	ncRNA	100499489
BMI1	protein-coding	648
SPAG6	protein-coding	9576

Protein

Protein identifiers

COMM domain-containing protein 3 — Q9UBI1 (reviewed: Q9UBI1)

Alternative names: Protein Bup, Protein PIL

All UniProt accessions (6): Q9UBI1, H0Y4E5, H0Y4W0, H0Y6Z9, R4GN06, R4GNF2

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex. May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits.

Subunit / interactions. Component of the commander complex consisting of the CCC subcomplex and the retriever subcomplex. Component of the CCC (COMMD/CCDC22/CCDC93) subcomplex consisting of COMMD1, COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8, COMMD9, COMMD10, CCDC22 and CCDC93; within the complex forms a heterodimer with COMMD2. Interacts with NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4A, CUL4B, CUL5.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed with highest expression in thymus.

Similarity. Belongs to the COMM domain-containing protein 3 family.

RefSeq proteins (1): NP_036203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017920	COMM	Domain
IPR037355	COMMD3	Family

Pfam: PF07258, PF21672

UniProt features (15 total): helix 6, strand 3, turn 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
8P0W	Structure of the human Commander complex COMMD ring	ELECTRON MICROSCOPY	2.9
8F2R	Human CCC complex	ELECTRON MICROSCOPY	3.12
8F2U	Human CCC complex	ELECTRON MICROSCOPY	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBI1-F1	86.84	0.63

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-8951664	Neddylation	—
R-HSA-6798695	Neutrophil degranulation	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 178 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOCC_SECRETORY_GRANULE, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, USF_01, TGACATY_UNKNOWN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, AACTTT_UNKNOWN, BENPORATH_NOS_TARGETS, GOBP_ENDOCYTIC_RECYCLING, USF_02, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (4): DNA-templated transcription (GO:0006351), sodium ion transport (GO:0006814), endocytic recycling (GO:0032456), monoatomic ion transport (GO:0006811)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), nucleus (GO:0005634), endosome membrane (GO:0010008), protein-containing complex (GO:0032991), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Innate Immune System	1
Post-translational protein modification	1
Immune System	1
Metabolism of proteins	1

GO top-level categories

19 GO namespaces:

Category	Terms
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
metal ion transport	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
transport	1
binding	1
intracellular membrane-bounded organelle	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular_component	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
protein-containing complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,021 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD3	COMMD2	Q86X83	809
COMMD3	COMMD4	Q9H0A8	771
COMMD3	COMMD8	Q9NX08	771
COMMD3	COMMD5	Q9GZQ3	756
COMMD3	COMMD9	Q9P000	736
COMMD3	CCDC22	O60826	720
COMMD3	COMMD1	Q8N668	716
COMMD3	CCDC93	Q567U6	690
COMMD3	COMMD6	Q7Z4G1	684
COMMD3	COMMD10	Q9Y6G5	683
COMMD3	A0A2R8Y455	A0A2R8Y455	644
COMMD3	COMMD7	Q86VX2	634
COMMD3	DENND10	Q8TCE6	632
COMMD3	VPS35L	Q7Z3J2	631
COMMD3	VPS26C	O14972	599

IntAct

Human interaction partners of COMMD3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 76 partners by confidence:

Partner	Interaction type	MIscore	Records
CCDC22	physical association	0.930	1
COMMD2	physical association	0.900	3
COMMD1	physical association	0.880	2
CCDC93	physical association	0.850	1
COMMD8	physical association	0.840	1
VPS26C	association	0.640	5
AHNAK	direct interaction	0.590	1
PIH1D2	physical association	0.560	5
PATJ	direct interaction	0.440	7
GRIP2	direct interaction	0.440	4
DLG4	direct interaction	0.440	3
GRIP1	direct interaction	0.440	3
IL16	direct interaction	0.440	3
MAGI2	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
NHERF4	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG1	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
LNX1	direct interaction	0.440	2
PDZK1	direct interaction	0.440	2
WHRN	direct interaction	0.440	2
APBA3	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF11	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1
CARD11	direct interaction	0.440	1
CASK	direct interaction	0.440	1
DLG3	direct interaction	0.440	1

BioGRID (157 interactions; top human partners by supporting records): COMMD2 (Affinity Capture-MS; 7 records), COMMD8 (Affinity Capture-MS; 7 records), CCDC22 (Affinity Capture-MS; 6 records), COMMD1 (Affinity Capture-MS; 6 records), COMMD10 (Affinity Capture-MS; 6 records), CCDC93 (Affinity Capture-MS; 5 records), COMMD6 (Affinity Capture-MS; 5 records), COMMD9 (Affinity Capture-MS; 5 records), C16orf62 (Affinity Capture-MS; 4 records), COMMD4 (Affinity Capture-MS; 4 records), COMMD7 (Affinity Capture-MS; 4 records), DSCR3 (Affinity Capture-MS; 4 records), CCDC151 (Affinity Capture-MS; 3 records), CD33 (Affinity Capture-MS; 3 records), COMMD5 (Affinity Capture-MS; 3 records)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
CCC-Wash (WASH1, FAM21C) complex	15	COMMD3, COMMD4, CCDC22, COMMD1, COMMD8, WASHC1, WASHC2C, CCDC93, COMMD10, COMMD2, COMMD5, COMMD7, COMMD6, COMMD9, VPS35L
CCC complex	13	COMMD2, COMMD3, COMMD6, COMMD8, VPS35L, CCDC93, COMMD1, COMMD10, COMMD4, COMMD5, COMMD7, COMMD9, CCDC22

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Assembly and cell surface presentation of NMDA receptors	8	39.8×	2e-09
Neurexins and neuroligins	9	34.8×	7e-10
Protein-protein interactions at synapses	6	31.2×	2e-06
RHOA GTPase cycle	5	7.3×	6e-03
Neuronal System	6	5.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	78.5×	1e-14
protein localization to synapse	5	51.8×	4e-06
receptor clustering	6	50.6×	4e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	40.2×	1e-06
protein-containing complex assembly	9	13.8×	2e-06
cell-cell adhesion	7	9.6×	4e-04
chemical synaptic transmission	6	6.3×	8e-03
protein transport	8	4.7×	7e-03

Disease & clinical

Genetic variants

Variant evidence for COMMD3: 9 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 593):

Position(s)	Effect	Δscore	Sites
10:22316557–22316558	donor_loss	1.0000	4
10:22318441	donor_gain	1.0000
10:22316557	donor_loss	0.9900
10:22317996–22317997	donor_loss	0.9800	6
10:22318423	donor_gain	0.9700
10:22318873	donor_gain	0.9600
10:22316553	donor_gain	0.9500
10:22317881–22317883	acceptor_loss	0.9500	6
10:22317883	acceptor_loss	0.9400
10:22317995	donor_loss	0.9400

AlphaMissense

254 missense substitutions predicted likely pathogenic (of 1,280 scored), across 82 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
F168	8	0.827	0.964
D177	8	0.774	0.896
D184	8	0.759	0.940
W130	7	0.961	0.995
C170	6	0.861	0.978
F25	6	0.807	0.924
K183	5	0.873	0.953
K187	5	0.861	0.927
K75	5	0.840	0.940
K60	5	0.819	0.888
Y104	5	0.813	0.960
F100	5	0.795	0.900
G180	5	0.722	0.841
E72	5	0.699	0.771
D127	5	0.691	0.825
Y149	4	0.905	0.975
F33	4	0.901	0.931
L182	4	0.881	0.989
Q176	4	0.855	0.926
R191	4	0.797	0.881

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	7.06e-08
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.56e-06
Glioblastoma Multiforme (validation)	favorable	5.16e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000601

Disease associations

OMIM: gene MIM:616700 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST004093_34	Prostate-specific antigen levels	1e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	5
Tobacco Smoke Pollution	decreases expression	2
dicrotophos	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	decreases expression	1
cupric chloride	decreases expression	1
nickel sulfate	decreases expression	1
1-nitropyrene	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects expression	1
Dimethyl Sulfoxide	decreases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Vitamin E	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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