COMMD2

Summary

COMMD2 (COMM domain containing 2, HGNC:24993) is a protein-coding gene on chromosome 3q25.1, encoding COMM domain-containing protein 2 (Q86X83). 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. Part of protein-containing complex.

Source: NCBI Gene 51122 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 39 total — 2 pathogenic
• GTEx eGene: eQTL in 48 tissues, sQTL in 42 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.61 (unconstrained)
• MANE Select transcript: NM_016094

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24993
Approved symbol	COMMD2
Name	COMM domain containing 2
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPC042
Ensembl gene	ENSG00000114744
Ensembl biotype	protein_coding
OMIM	616699
Entrez	51122

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

MANE Select: ENST00000473414

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

ENST00000473414, ENST00000463077, ENST00000469896, ENST00000483146, ENST00000483708, ENST00000490008, ENST00000491617, ENST00000857322, ENST00000857323, ENST00000857324, ENST00001077750, ENST00001098314, ENST00001107381, ENST00001143971

RefSeq mRNA: 1 — MANE Select: NM_016094 NM_016094

CCDS: CCDS3145

Canonical transcript exons

ENST00000473414 — 5 exons

Exon	Start	End
ENSE00001236671	149738472	149741718
ENSE00001841520	149752378	149752489
ENSE00003500482	149751403	149751485
ENSE00003507772	149752210	149752287
ENSE00003512830	149750678	149750851

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3070 / max 310.2371, expressed in 1791 samples.

Highest expression (Bgee): secondary oocyte, oocyte, cortical plate, endothelial cell, upper arm skin.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COMMD2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 48 tissues and its splicing (sQTL) in 42 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 90 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	2.7e-64	-1.38	3:149750354:G:A
Artery Tibial	sqtl	1.6e-50	-1.90	3:149750354:G:A
Thyroid	sqtl	2.3e-48	-1.90	3:149750354:G:A
Cells Cultured fibroblasts	eqtl	1.0e-44	+0.34	3:149757558:T:C
Skin Sun Exposed Lower leg	sqtl	6.3e-42	-1.70	3:149750354:G:A
Nerve Tibial	eqtl	1.1e-37	+0.31	3:149739208:C:G
Esophagus Muscularis	eqtl	3.4e-34	+0.35	3:149760473:C:A
Adipose Subcutaneous	eqtl	9.8e-32	+0.35	3:149757558:T:C
Adipose Subcutaneous	sqtl	3.0e-30	-1.62	3:149750354:G:A
Esophagus Mucosa	sqtl	1.6e-29	-1.69	3:149750354:G:A
Esophagus Muscularis	sqtl	3.0e-29	-1.62	3:149750354:G:A
Brain Spinal cord cervical c-1	eqtl	9.0e-28	+0.59	3:149741554:A:G
Esophagus Gastroesophageal Junction	eqtl	2.8e-23	+0.39	3:149746640:A:G
Breast Mammary Tissue	sqtl	4.9e-23	-1.50	3:149750354:G:A
Lung	sqtl	8.2e-23	+1.34	3:149750354:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-22	+0.24	3:149747663:G:A
Brain Cerebellar Hemisphere	sqtl	1.3e-22	-2.16	3:149750354:G:A
Cells EBV-transformed lymphocytes	sqtl	9.7e-22	+1.76	3:149750354:G:A
Colon Transverse	sqtl	2.0e-21	-1.75	3:149750354:G:A
Skin Not Sun Exposed Suprapubic	sqtl	2.4e-21	+1.26	3:149750354:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
45058	18.3070	1791

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.44	gold quality
oocyte	CL:0000023	96.43	gold quality
cortical plate	UBERON:0005343	96.01	gold quality
endothelial cell	CL:0000115	95.37	silver quality
upper arm skin	UBERON:0004263	94.93	gold quality
calcaneal tendon	UBERON:0003701	93.26	gold quality
parietal pleura	UBERON:0002400	92.81	gold quality
visceral pleura	UBERON:0002401	92.44	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.14	gold quality
left ventricle myocardium	UBERON:0006566	92.13	gold quality
germinal epithelium of ovary	UBERON:0001304	91.60	gold quality
epithelial cell of pancreas	CL:0000083	91.46	gold quality
palpebral conjunctiva	UBERON:0001812	91.30	gold quality
pigmented layer of retina	UBERON:0001782	91.24	gold quality
layer of synovial tissue	UBERON:0007616	90.82	gold quality
smooth muscle tissue	UBERON:0001135	90.70	gold quality
tibia	UBERON:0000979	90.69	gold quality
monocyte	CL:0000576	90.51	gold quality
amniotic fluid	UBERON:0000173	90.31	gold quality
synovial joint	UBERON:0002217	90.11	gold quality
leukocyte	CL:0000738	90.04	gold quality
penis	UBERON:0000989	89.98	gold quality
epithelium of mammary gland	UBERON:0003244	89.75	gold quality
endometrium	UBERON:0001295	89.74	gold quality
islet of Langerhans	UBERON:0000006	89.70	gold quality
mammary duct	UBERON:0001765	89.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.49	gold quality
corpus callosum	UBERON:0002336	89.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.37	gold quality
skin of hip	UBERON:0001554	89.33	gold quality
ganglionic eminence	UBERON:0004023	89.31	gold quality
esophagus squamous epithelium	UBERON:0006920	89.23	gold quality
tendon	UBERON:0000043	89.15	gold quality
adrenal tissue	UBERON:0018303	89.11	gold quality
ventricular zone	UBERON:0003053	89.03	gold quality
bone marrow cell	CL:0002092	89.00	gold quality
thoracic mammary gland	UBERON:0005200	88.81	gold quality
mammary gland	UBERON:0001911	88.79	gold quality
placenta	UBERON:0001987	88.01	gold quality
urethra	UBERON:0000057	87.89	gold quality
stromal cell of endometrium	CL:0002255	87.79	gold quality
uterus	UBERON:0000995	87.69	gold quality
oviduct epithelium	UBERON:0004804	87.63	gold quality
subthalamic nucleus	UBERON:0001906	87.54	gold quality
myocardium	UBERON:0002349	87.27	gold quality
rectum	UBERON:0001052	87.16	gold quality
middle temporal gyrus	UBERON:0002771	87.12	gold quality
bone marrow	UBERON:0002371	87.10	gold quality
inferior vagus X ganglion	UBERON:0005363	86.89	gold quality
female reproductive system	UBERON:0000474	86.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.74	gold quality
upper leg skin	UBERON:0004262	86.68	gold quality
ovary	UBERON:0000992	86.63	gold quality
metanephros	UBERON:0000081	86.60	gold quality
superficial temporal artery	UBERON:0001614	86.57	gold quality
lung	UBERON:0002048	86.55	gold quality
vermiform appendix	UBERON:0001154	86.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.38	gold quality
myometrium	UBERON:0001296	86.34	gold quality
lymph node	UBERON:0000029	85.94	gold quality
oral cavity	UBERON:0000167	85.78	gold quality
dorsal root ganglion	UBERON:0000044	85.74	gold quality
fallopian tube	UBERON:0003889	85.73	gold quality
body of uterus	UBERON:0009853	85.70	gold quality
bronchial epithelial cell	CL:0002328	85.69	gold quality
tonsil	UBERON:0002372	85.69	gold quality
nasal cavity mucosa	UBERON:0001826	85.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.60	gold quality
pancreas	UBERON:0001264	85.58	gold quality
occipital lobe	UBERON:0002021	85.55	gold quality
spinal cord	UBERON:0002240	85.50	gold quality
primary visual cortex	UBERON:0002436	85.49	gold quality
caecum	UBERON:0001153	85.43	gold quality
left ovary	UBERON:0002119	85.42	gold quality
bronchus	UBERON:0002185	85.39	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.14	gold quality
right ovary	UBERON:0002118	85.10	gold quality
epithelium of nasopharynx	UBERON:0001951	85.07	gold quality
minor salivary gland	UBERON:0001830	85.06	gold quality
vagina	UBERON:0000996	85.04	gold quality
thymus	UBERON:0002370	85.00	gold quality
adipose tissue	UBERON:0001013	84.99	gold quality
lower lobe of lung	UBERON:0008949	84.96	gold quality
mouth mucosa	UBERON:0003729	84.93	gold quality
upper lobe of left lung	UBERON:0008952	84.88	gold quality
upper lobe of lung	UBERON:0008948	84.86	gold quality
trigeminal ganglion	UBERON:0001675	84.79	gold quality
deltoid	UBERON:0001476	84.70	gold quality
cauda epididymis	UBERON:0004360	84.59	gold quality
lateral globus pallidus	UBERON:0002476	84.58	gold quality
saphenous vein	UBERON:0007318	84.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.47	gold quality
kidney epithelium	UBERON:0004819	84.46	silver quality
thyroid gland	UBERON:0002046	84.45	gold quality
gingival epithelium	UBERON:0001949	84.34	gold quality
gingiva	UBERON:0001828	84.31	gold quality
left uterine tube	UBERON:0001303	84.29	gold quality
esophagus mucosa	UBERON:0002469	84.28	gold quality
uterine cervix	UBERON:0000002	84.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.43
E-CURD-97	no	532.52

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pons	tissue	24.8
Spinal cord	tissue	24.5
Thalamus	tissue	23.7
Superior colliculi	tissue	22.8
Cerebral cortex	tissue	22.7	medium
Occipital cortex	tissue	22.7
Somatosensory cortex	tissue	22.3
Medulla oblongata	tissue	22.2
Midbrain	tissue	21.9
Hippocampal formation	tissue	21.9
Substantia nigra	tissue	21.6
Motor cortex	tissue	21.1
Prefrontal cortex	tissue	20.4
Putamen	tissue	20.4
Entorhinal cortex	tissue	20.4
Retrosplenial and cingulate cortex	tissue	20.2
Periaqueductal gray	tissue	20.1
Hypothalamus	tissue	20.0
Septum	tissue	19.9
Corpus callosum	tissue	19.6
Retrosplenial cortex	tissue	19.5
Temporal cortex	tissue	19.2
Amygdala	tissue	17.7
Insular cortex	tissue	17.3
Ventral forebrain	tissue	17.2
Basal ganglia	tissue	17.1	medium
Olfactory bulb	tissue	16.8
Breast	tissue	14.2	medium
Cerebellum	tissue	14.2	medium
Ovary	tissue	13.3	medium
Thyroid gland	tissue	13.1	medium
Placenta	tissue	13.0	medium
Endometrium 1	tissue	12.6	medium
Lung	tissue	11.8	medium
Smooth muscle	tissue	11.5	medium
Thymus	tissue	11.4
Cervix	tissue	10.9	medium
Lymph node	tissue	10.1	medium
Retina	tissue	9.8
Kidney	tissue	9.8	medium
Tonsil	tissue	9.8	medium
Parathyroid gland	tissue	9.7	high
Spleen	tissue	9.5	medium
Postcentral gyrus	tissue	9.3
Skin 1	tissue	9.1	medium
Choroid plexus	tissue	9.0
Prostate	tissue	8.7	low
Nucleus accumbens	tissue	8.5
Liver	tissue	8.5	low
Esophagus	tissue	8.4	high
Bone marrow	tissue	8.3	medium
Heart muscle	tissue	8.0	medium
Seminal vesicle	tissue	7.9	medium
Rectum	tissue	7.9	high
Locus coeruleus	tissue	7.8
Fallopian tube	tissue	7.7	medium
Tongue	tissue	7.5
Adipose tissue	tissue	7.4	not detected
Duodenum	tissue	7.4	medium
Salivary gland	tissue	7.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Dorsal spinal cord (24.5), Ventral spinal cord (23.1), Dorsal hippocampus (21.9), Subiculum (20.1), White matter (19.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

Targeting COMMD2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 101 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893

Functional genomics

gnomAD constraint: pLI 5.69e-07, LOEUF 1.61, missense Z 0.288 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000473414 — one region, missense o/e 0.96.

Literature-anchored findings (GeneRIF, showing 1)

• Multi-omics analysis of the oncogenic value of copper Metabolism-Related protein COMMD2 in human cancers. (PMID:36205192)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	commd2	ENSDARG00000003373
mus_musculus	Commd2	ENSMUSG00000036513
rattus_norvegicus	Commd2	ENSRNOG00000043386
drosophila_melanogaster	CG7168	FBGN0038586

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
Pongo abelii	Q5R610	98.5%	Diamond
Dictyostelium discoideum	Q54P14	42.0%	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
WWTR1-IT1	ncRNA	106478977
WWTR1	protein-coding	25937
ANKUB1	protein-coding	389161
WWTR1-AS1	ncRNA	100128025
TM4SF4	protein-coding	7104
RNF13	protein-coding	11342
PFN2	protein-coding	5217

Protein

Protein identifiers

COMM domain-containing protein 2 — Q86X83 (reviewed: Q86X83)

All UniProt accessions (3): Q86X83, F8WBW1, F8WC41

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.

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 COMMD3. Interacts with RELA, RELB, NFKB1/p105, NFKB2/p100. Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4B, CUL5, CUL7.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the COMM domain-containing protein 2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86X83-1	1	yes
Q86X83-2	2

RefSeq proteins (1): NP_057178* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017920	COMM	Domain
IPR037354	Commd2	Family

Pfam: PF07258, PF21672

UniProt features (20 total): helix 11, strand 3, sequence variant 2, chain 1, domain 1, splice variant 1, sequence conflict 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-Q86X83-F1	89.00	0.57

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH uncertain · IF uncertain

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-392499	Metabolism of proteins	—
R-HSA-8951664	Neddylation	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 116 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GCM_DDX11, GOBP_ENDOCYTIC_RECYCLING, GOBP_LOCALIZATION_WITHIN_MEMBRANE, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, ACEVEDO_LIVER_CANCER_UP, LIU_SOX4_TARGETS_UP, GOCC_MEMBRANE_PROTEIN_COMPLEX, chr3q25, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_ENDOSOMAL_TRANSPORT

GO Biological Process (2): DNA-templated transcription (GO:0006351), endocytic recycling (GO:0032456)

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

GO Cellular Component (4): endosome membrane (GO:0010008), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

14 GO namespaces:

Category	Terms
gene expression	1
RNA biosynthetic process	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
binding	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular_component	1
intracellular anatomical structure	1
cellular 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 7 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 1,049 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD2	COMMD4	Q9H0A8	814
COMMD2	COMMD3	Q9UBI1	809
COMMD2	COMMD10	Q9Y6G5	789
COMMD2	COMMD9	Q9P000	786
COMMD2	COMMD8	Q9NX08	772
COMMD2	COMMD6	Q7Z4G1	756
COMMD2	COMMD5	Q9GZQ3	744
COMMD2	COMMD1	Q8N668	720
COMMD2	CCDC22	O60826	717
COMMD2	CCDC93	Q567U6	715
COMMD2	A0A2R8Y455	A0A2R8Y455	702
COMMD2	COMMD7	Q86VX2	701
COMMD2	DENND10	Q8TCE6	643
COMMD2	VPS35L	Q7Z3J2	639
COMMD2	VPS26C	O14972	594

IntAct

Human interaction partners of COMMD2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
CCDC22	physical association	0.930	4
COMMD3	physical association	0.900	3
COMMD1	physical association	0.870	1
CCDC93	physical association	0.850	1
COMMD4	physical association	0.820	1
VPS26C	association	0.640	1
SPRED1	physical association	0.560	3
NFKB1	association	0.350	1
PCBP2	association	0.350	1

BioGRID (165 interactions; top human partners by supporting records): CCDC22 (Co-fractionation; 7 records), COMMD1 (Co-fractionation; 7 records), COMMD10 (Co-fractionation; 7 records), COMMD3 (Affinity Capture-MS; 7 records), CCDC93 (Co-fractionation; 6 records), COMMD4 (Affinity Capture-MS; 6 records), COMMD8 (Co-fractionation; 6 records), COMMD6 (Affinity Capture-MS; 5 records), C16orf62 (Affinity Capture-MS; 4 records), COMMD5 (Co-fractionation; 4 records), VPS29 (Affinity Capture-MS; 4 records), CCDC151 (Affinity Capture-MS; 3 records), COMMD7 (Affinity Capture-MS; 3 records), COMMD9 (Affinity Capture-MS; 3 records), DSCR3 (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

Disease & clinical

Genetic variants

Variant evidence for COMMD2: 39 ClinVar records (2 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1047879	GRCh37/hg19 3q22.3-26.1(chr3:138173683-162494699)	Pathogenic	criteria provided, single submitter	1
1459543	NC_000003.11:g.(?148447967)(151176497_?)del	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore COMMD2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 16 predictions of 426):

Position(s)	Effect	Δscore	Sites
3:149750676–149750677	donor_loss	1.0000	5
3:149750813	acceptor_gain	1.0000
3:149750853	acceptor_loss	1.0000
3:149751486	acceptor_gain	1.0000
3:149751487	acceptor_loss	1.0000	2
3:149751499	acceptor_gain	1.0000
3:149752193	donor_gain	1.0000
3:149752200	donor_gain	1.0000
3:149741725–149741726	acceptor_gain	0.9900	2
3:149750853	acceptor_loss	0.9900

AlphaMissense

403 missense substitutions predicted likely pathogenic (of 1,305 scored), across 131 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
F27	8	0.891	0.984
F82	8	0.887	0.992
D132	8	0.844	0.942
W129	7	0.984	0.999
F91	7	0.870	0.972
E26	7	0.859	0.976
H12	7	0.774	0.873
R138	6	0.938	0.978
G38	6	0.894	0.962
K50	6	0.868	0.941
A47	6	0.865	0.997
K42	6	0.860	0.938
V62	6	0.795	0.985
V23	6	0.791	0.906
D168	6	0.652	0.718
D81	6	0.622	0.670
S72	5	0.931	0.996
G28	5	0.897	0.985
S137	5	0.894	0.943
R193	5	0.891	0.950

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.8e-06
Glioblastoma Multiforme (TCGA)	favorable	0.000171
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000185
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.00045
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000459
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000748

Disease associations

OMIM: gene MIM:616699 | disease phenotypes: MIM:613507, MIM:616199

GenCC curated gene-disease

Mondo (2): glycogen storage disease XV (MONDO:0013291), polyglucosan body myopathy type 2 (MONDO:0014526)

Orphanet (2): Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency (Orphanet:263297), Polyglucosan body myopathy type 2 (Orphanet:456369)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
ochratoxin A	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carcinogens	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ketoconazole	decreases expression	1
Mutagens	decreases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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

1 trials:

NCT	Phase	Status	Title
NCT06795152	Not specified	RECRUITING	Rare Glycogen Storage Diseases Natural History Study