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 located in cytoplasm.

Source: NCBI Gene 51122 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total — 2 pathogenic
• 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: 10 — 4 retained_intron, 4 protein_coding, 2 nonsense_mediated_decay

ENST00000463077, ENST00000469896, ENST00000473414, ENST00000483146, ENST00000483708, ENST00000490008, ENST00000491617, ENST00000857322, ENST00000857323, ENST00000857324

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45058	18.3070	1791

Top tissues by expression

256 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

101 targeting COMMD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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

Protein

Protein identifiers

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

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

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 (19 total): helix 10, strand 3, sequence variant 2, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8P0W	ELECTRON MICROSCOPY	2.9
8F2R	ELECTRON MICROSCOPY	3.12
8F2U	ELECTRON MICROSCOPY	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86X83-F1	89.00	0.57

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

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 (0):

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

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1043 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD2	COMMD3	Q9UBI1	858
COMMD2	COMMD4	Q9H0A8	832
COMMD2	COMMD9	Q9P000	747
COMMD2	CCDC22	O60826	745
COMMD2	COMMD10	Q9Y6G5	743
COMMD2	COMMD6	Q7Z4G1	726
COMMD2	COMMD5	Q9GZQ3	711
COMMD2	COMMD8	Q9NX08	710
COMMD2	A0A2R8Y455	A0A2R8Y455	705
COMMD2	COMMD7	Q86VX2	702
COMMD2	VPS26C	O14972	680
COMMD2	COMMD1	Q8N668	671
COMMD2	ANKUB1	A6NFN9	618
COMMD2	WDR81	Q562E7	572
COMMD2	ATP7B	P35670	539

IntAct

95 interactions, top by confidence:

A	B	Type	Score
CCDC22	CCDC93	psi-mi:“MI:0915”(physical association)	0.960
CCDC22	CCDC93	psi-mi:“MI:0914”(association)	0.960
COMMD1	COMMD6	psi-mi:“MI:0915”(physical association)	0.950
CCDC22	COMMD2	psi-mi:“MI:0915”(physical association)	0.930
CCDC22	COMMD6	psi-mi:“MI:0914”(association)	0.930
COMMD2	CCDC22	psi-mi:“MI:0914”(association)	0.930
COMMD2	COMMD3	psi-mi:“MI:0915”(physical association)	0.900
COMMD2	COMMD1	psi-mi:“MI:0915”(physical association)	0.870
COMMD2	CCDC93	psi-mi:“MI:0915”(physical association)	0.850
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
COMMD2	COMMD4	psi-mi:“MI:0915”(physical association)	0.820
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
VPS26C	CCDC22	psi-mi:“MI:0914”(association)	0.790
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD8	COMMD6	psi-mi:“MI:0914”(association)	0.730
VPS35L	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
TRIM16L	CCDC22	psi-mi:“MI:0914”(association)	0.640
COMMD3	VPS26C	psi-mi:“MI:0914”(association)	0.640

BioGRID (160): COMMD2 (Affinity Capture-MS), COMMD2 (Affinity Capture-MS), COMMD2 (Affinity Capture-MS), COMMD2 (Affinity Capture-MS), COMMD2 (Affinity Capture-MS), ARHGAP17 (Co-fractionation), COMMD1 (Co-fractionation), COMMD2 (Co-fractionation), COMMD2 (Co-fractionation), COMMD2 (Co-fractionation), COMMD2 (Co-fractionation), COMMD4 (Co-fractionation), COMMD5 (Co-fractionation), COMMD8 (Co-fractionation), MCMBP (Co-fractionation)

ESM2 similar proteins: A2RT67, A2RUS2, A3KMX7, A5PJM5, A5PKL6, A6QPR9, A7E2V1, B1H268, E9PYK3, O43543, Q05AX3, Q08CZ0, Q0IHA2, Q0VCL9, Q28DH9, Q3TLI0, Q3ZC98, Q4R6Y8, Q5F204, Q5I0G3, Q5JPI3, Q5R4T7, Q5R610, Q5R8P3, Q5RC62, Q5RL51, Q5SUD9, Q5ZJV4, Q68EI0, Q6DDX8, Q6DG91, Q6PBN5, Q6PGF3, Q6ZW61, Q7TNH6, Q7Z494, Q86X83, Q8BXC6, Q8NEC7, Q8R3C0

Diamond homologs: Q54P14, Q5R610, Q86X83, Q8BXC6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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
Neddylation	10	12.2×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
Golgi to plasma membrane transport	5	48.4×	2e-05
endocytic recycling	6	27.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

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)

Variant ID	HGVS	Classification
1047879	GRCh37/hg19 3q22.3-26.1(chr3:138173683-162494699)	Pathogenic
1459543	NC_000003.11:g.(?148447967)(151176497_?)del	Pathogenic

SpliceAI

730 predictions. Top by Δscore:

Variant	Effect	Δscore
3:149750672:CTATA:C	donor_loss	1.0000
3:149750673:TATA:T	donor_loss	1.0000
3:149750675:TAC:T	donor_loss	1.0000
3:149750677:C:T	donor_loss	1.0000
3:149750813:C:CT	acceptor_gain	1.0000
3:149750813:C:T	acceptor_gain	1.0000
3:149750851:TCTA:T	acceptor_loss	1.0000
3:149750852:C:CC	acceptor_gain	1.0000
3:149751481:TTTTC:T	acceptor_gain	1.0000
3:149751482:TTTC:T	acceptor_gain	1.0000
3:149751483:TTC:T	acceptor_gain	1.0000
3:149751484:TC:T	acceptor_gain	1.0000
3:149751484:TCC:T	acceptor_loss	1.0000
3:149751485:CC:C	acceptor_gain	1.0000
3:149751486:C:CC	acceptor_gain	1.0000
3:149751486:C:T	acceptor_gain	1.0000
3:149751487:T:A	acceptor_loss	1.0000
3:149751499:G:C	acceptor_gain	1.0000
3:149752192:T:TA	donor_gain	1.0000
3:149752193:C:A	donor_gain	1.0000
3:149752200:C:A	donor_gain	1.0000
3:149752208:A:AC	donor_gain	1.0000
3:149752209:C:CT	donor_gain	1.0000
3:149752209:CTGG:C	donor_gain	1.0000
3:149752288:C:CC	acceptor_gain	1.0000
3:149752369:C:CA	donor_gain	1.0000
3:149752374:TGA:T	donor_loss	1.0000
3:149752375:GAC:G	donor_loss	1.0000
3:149752377:C:CT	donor_loss	1.0000
3:149752413:T:TA	donor_gain	1.0000

AlphaMissense

1305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:149750695:A:G	W129R	0.999
3:149750695:A:T	W129R	0.999
3:149751458:A:T	V58D	0.999
3:149750691:C:G	R130P	0.997
3:149752212:G:T	A48D	0.997
3:149752215:G:T	A47D	0.997
3:149752263:G:T	A31D	0.997
3:149751415:G:C	S72R	0.996
3:149751415:G:T	S72R	0.996
3:149751417:T:G	S72R	0.996
3:149751428:A:G	L68P	0.996
3:149751441:C:G	G64R	0.996
3:149751441:C:T	G64R	0.996
3:149752213:C:G	A48P	0.996
3:149752264:C:G	A31P	0.996
3:149750693:C:A	W129C	0.994
3:149750693:C:G	W129C	0.994
3:149751425:A:G	L69P	0.993
3:149751440:C:T	G64E	0.993
3:149741606:A:G	L172P	0.992
3:149741715:C:G	A136P	0.992
3:149750835:A:G	F82S	0.992
3:149741585:A:G	L179P	0.991
3:149741666:A:G	L152P	0.991
3:149752407:A:G	L13P	0.991
3:149750688:A:G	L131P	0.990
3:149750694:C:G	W129S	0.989
3:149750700:A:G	L127P	0.989
3:149741577:C:G	A182P	0.988
3:149750710:A:C	Y124D	0.988

dbSNP variants (sampled 300 via entrez): RS1000010538 (3:149752851 A>G), RS1000660101 (3:149754237 C>G), RS1001009365 (3:149741153 T>G), RS1001162663 (3:149748283 A>C), RS1001231191 (3:149752513 G>C), RS1001259857 (3:149748000 G>A), RS1001472605 (3:149744731 A>C), RS1001683323 (3:149737991 A>G), RS1001775359 (3:149745058 G>A), RS1001861545 (3:149746534 G>C), RS1001947060 (3:149752856 A>C,G), RS1002013420 (3:149739631 C>T), RS1002041158 (3:149739198 C>G,T), RS1002113855 (3:149746775 C>T), RS1002324532 (3:149738598 T>C)

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)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

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	affects cotreatment, increases expression	1
Ketoconazole	decreases expression	1
Mutagens	decreases expression	1
Ozone	increases abundance, affects expression	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	decreases expression, increases abundance	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

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