COMMD7

Summary

COMMD7 (COMM domain containing 7, HGNC:16223) is a protein-coding gene on chromosome 20q11.21, encoding COMM domain-containing protein 7 (Q86VX2). 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.

Enables NF-kappaB binding activity. Involved in negative regulation of DNA-templated transcription; negative regulation of NF-kappaB transcription factor activity; and tumor necrosis factor-mediated signaling pathway. Predicted to be located in cytoplasmic vesicle and membrane.

Source: NCBI Gene 149951 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_053041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16223
Approved symbol	COMMD7
Name	COMM domain containing 7
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ1085F17.3
Ensembl gene	ENSG00000149600
Ensembl biotype	protein_coding
OMIM	616703
Entrez	149951

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 nonsense_mediated_decay

ENST00000278980, ENST00000446419, ENST00000474815, ENST00000610160, ENST00000855714, ENST00000855715, ENST00000855716, ENST00000855717, ENST00000855718, ENST00000855719, ENST00000855720, ENST00000855721, ENST00000934209, ENST00000941360, ENST00000941361

RefSeq mRNA: 2 — MANE Select: NM_053041 NM_001099339, NM_053041

CCDS: CCDS42864, CCDS46587

Canonical transcript exons

ENST00000278980 — 9 exons

Exon	Start	End
ENSE00000991593	32727893	32727995
ENSE00001410899	32706704	32706760
ENSE00001412355	32704814	32704904
ENSE00001415666	32706583	32706620
ENSE00001416942	32704023	32704071
ENSE00001418691	32704440	32704489
ENSE00001934565	32702699	32703458
ENSE00001935121	32743308	32743467
ENSE00003709481	32728089	32728142

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0360 / max 206.2583, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186939	17.8746	1813
186940	4.8137	1631
186941	1.0852	323
186942	0.2625	103

Top tissues by expression

257 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	96.98	gold quality
left ventricle myocardium	UBERON:0006566	96.81	gold quality
middle temporal gyrus	UBERON:0002771	95.91	gold quality
upper arm skin	UBERON:0004263	95.85	gold quality
deltoid	UBERON:0001476	95.76	gold quality
epithelial cell of pancreas	CL:0000083	95.49	silver quality
quadriceps femoris	UBERON:0001377	95.34	gold quality
vastus lateralis	UBERON:0001379	95.19	gold quality
placenta	UBERON:0001987	95.19	gold quality
pancreatic ductal cell	CL:0002079	95.15	gold quality
right lobe of thyroid gland	UBERON:0001119	95.12	gold quality
parotid gland	UBERON:0001831	95.08	gold quality
nasal cavity epithelium	UBERON:0005384	95.05	gold quality
ileal mucosa	UBERON:0000331	95.01	gold quality
anterior cingulate cortex	UBERON:0009835	94.97	gold quality
tibialis anterior	UBERON:0001385	94.83	silver quality
right frontal lobe	UBERON:0002810	94.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.82	gold quality
left lobe of thyroid gland	UBERON:0001120	94.79	gold quality
cortical plate	UBERON:0005343	94.77	gold quality
granulocyte	CL:0000094	94.72	gold quality
heart left ventricle	UBERON:0002084	94.70	gold quality
cardiac ventricle	UBERON:0002082	94.69	gold quality
apex of heart	UBERON:0002098	94.67	gold quality
amygdala	UBERON:0001876	94.65	gold quality
biceps brachii	UBERON:0001507	94.64	gold quality
myocardium	UBERON:0002349	94.57	gold quality
visceral pleura	UBERON:0002401	94.56	gold quality
thyroid gland	UBERON:0002046	94.48	gold quality
heart right ventricle	UBERON:0002080	94.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR2, SOX10, TFAP2A

miRNA regulators (miRDB)

34 targeting COMMD7, 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-5196-5P	100.00	67.98	2761
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-656-5P	96.82	67.67	372

Literature-anchored findings (GeneRIF, showing 10)

• BC047440 can promote the growth and invasion of hepatocellular carcinoma. (PMID:20979692)
• COMMD7 contributes to hepatocellular carcinoma progression by reducing cell apoptosis and overcoming cell cycle arrest. (PMID:23049798)
• COMMD7’s binding to NEMO does not interfere with the binding to the IKKs, and that the disruption of the IKK complex through the use of the NBP competitor impairs the termination of NF-kappaB activity (PMID:26060140)
• COMMD7 up-regulation is correlated with a novel NF-kappaB positive feedback loop in hepatocellular carcinoma, regulation cell proliferation, cell migration and apoptosis. (PMID:27129158)
• High COMMD7 expression was specifically detected in pancreatic ductal adenocarcinoma tissues and pancreatic ductal adenocarcinoma cell lines. In addition, COMMD7 overexpression positively correlated with histological differentiation and tumor node metastasis (TNM) stage. (PMID:27350032)
• The present data suggests a potential role of CXCL10 in the oncogenic function of COMMD7. (PMID:28142122)
• COMMD7 activates CXCL10 production by regulating NFkappaB and the production of ROS. The present study highlighted the role of COMMD7 in the development of HCC, and provides novel options for anticancer drug design. (PMID:29532873)
• High expression of COMMD7 is an adverse prognostic factor in acute myeloid leukemia. (PMID:33891561)
• Linc00852 from cisplatin-resistant gastric cancer cell-derived exosomes regulates COMMD7 to promote cisplatin resistance of recipient cells through microRNA-514a-5p. (PMID:35088190)
• ZNF460-regulated COMMD7 Promotes Acute Myeloid Leukemia Proliferation Via the NF-kappaB Signaling Pathway. (PMID:37057209)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	commd7	ENSDARG00000036784
mus_musculus	Commd7	ENSMUSG00000056941
rattus_norvegicus	Commd7	ENSRNOG00000010538

Paralogs (2): COMMD8 (ENSG00000169019), COMMD6 (ENSG00000188243)

Protein

Protein identifiers

COMM domain-containing protein 7 — Q86VX2 (reviewed: Q86VX2)

All UniProt accessions (3): Q86VX2, V9GY66, V9GYC5

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. Associates with the NF-kappa-B complex and suppresses its transcriptional activity.

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 COMMD9. Interacts with RELA. Interacts with CCDC22, CCDC93, SCNN1B, CUL7.

Subcellular location. Cytoplasmic vesicle.

Tissue specificity. Widely expressed with highest expression in lung.

Similarity. Belongs to the COMM domain-containing protein 7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86VX2-1	1	yes
Q86VX2-2	2

RefSeq proteins (2): NP_001092809, NP_444269* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017920	COMM	Domain
IPR037358	COMMD7	Family
IPR047155	COMMD4/6/7/8	Family

Pfam: PF07258, PF21672

UniProt features (16 total): helix 7, strand 3, sequence conflict 3, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8P0W	ELECTRON MICROSCOPY	2.9
8F2R	ELECTRON MICROSCOPY	3.12
8ESD	X-RAY DIFFRACTION	3.33
8F2U	ELECTRON MICROSCOPY	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VX2-F1	84.76	0.39

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 117 (showing top): GOBP_RESPONSE_TO_PEPTIDE, MODULE_493, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_NF_KAPPAB_TRANSCRIPTION_FACTOR_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, BENPORATH_NOS_TARGETS, GOBP_ENDOCYTIC_RECYCLING, chr20q11, GOBP_LOCALIZATION_WITHIN_MEMBRANE, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_RESPONSE_TO_TUMOR_NECROSIS_FACTOR, HU_GENOTOXIC_DAMAGE_4HR, BENPORATH_OCT4_TARGETS, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (3): obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), tumor necrosis factor-mediated signaling pathway (GO:0033209), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (2): NF-kappaB binding (GO:0051059), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasmic vesicle (GO:0031410), membrane (GO:0016020)

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
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
binding	1
cytoplasm	1
intracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD7	IARS1	P41252	840
COMMD7	PNRC2	Q9NPJ4	826
COMMD7	COMMD9	Q9P000	711
COMMD7	COMMD10	Q9Y6G5	709
COMMD7	COMMD2	Q86X83	702
COMMD7	COMMD5	Q9GZQ3	699
COMMD7	DCP1A	Q9NPI6	681
COMMD7	UPF1	Q92900	649
COMMD7	COMMD1	Q8N668	598
COMMD7	COMMD8	Q9NX08	553
COMMD7	MAPRE1	Q15691	530
COMMD7	COMMD3	Q9UBI1	523
COMMD7	COMMD6	Q7Z4G1	518
COMMD7	COMMD4	Q9H0A8	506
COMMD7	ESRRG	P62508	495

IntAct

64 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	COMMD6	psi-mi:“MI:0914”(association)	0.930
COMMD2	CCDC22	psi-mi:“MI:0914”(association)	0.930
COMMD7	CCDC22	psi-mi:“MI:0915”(physical association)	0.890
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
VPS26C	CCDC22	psi-mi:“MI:0914”(association)	0.790
COMMD1	COMMD7	psi-mi:“MI:0915”(physical association)	0.770
DENND10	CCDC93	psi-mi:“MI:0914”(association)	0.770
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
VPS35L	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
VPS29	VPS26B	psi-mi:“MI:0914”(association)	0.730
COMMD5	COMMD7	psi-mi:“MI:0915”(physical association)	0.680
COMMD7	CCDC93	psi-mi:“MI:0915”(physical association)	0.670
COMMD3	VPS26C	psi-mi:“MI:0914”(association)	0.640
CCDC93	VPS26C	psi-mi:“MI:0914”(association)	0.640

BioGRID (57): COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-MS), COMMD1 (Co-fractionation), COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-Western), COMMD1 (Affinity Capture-Western), COMMD6 (Affinity Capture-Western), CHUK (Affinity Capture-Western), IKBKB (Affinity Capture-Western), COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-MS), COMMD7 (Affinity Capture-MS)

ESM2 similar proteins: A4FUC9, A8MT19, B0BM28, B0BN28, F1S5L4, F2Z461, F4I735, P0DM65, P97564, Q05AV1, Q08BZ4, Q0V7M7, Q0WVH0, Q1LXZ7, Q28HC7, Q2M2T5, Q3MHX1, Q3SYG4, Q3SZ76, Q550I8, Q5GJ77, Q5ZJC7, Q61586, Q63829, Q68F70, Q6DJJ6, Q6P5U7, Q6P9U3, Q6PBQ2, Q7M6Y6, Q7Z745, Q811G0, Q86VX2, Q8BG94, Q8BWR8, Q8CIM8, Q8HXG3, Q8IUC4, Q8N668, Q8R395

Diamond homologs: Q3MHX1, Q86I14, Q86VX2, Q8BG94

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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	9	18.5×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
endocytic recycling	6	53.5×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1568 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32704072:C:CC	acceptor_gain	1.0000
20:32704075:A:AC	acceptor_gain	1.0000
20:32704075:A:C	acceptor_gain	1.0000
20:32704438:A:AC	donor_gain	1.0000
20:32704439:C:CC	donor_gain	1.0000
20:32704490:C:CC	acceptor_gain	1.0000
20:32704809:GTTAC:G	donor_loss	1.0000
20:32704810:TTAC:T	donor_loss	1.0000
20:32704811:TA:T	donor_loss	1.0000
20:32704812:AC:A	donor_loss	1.0000
20:32704813:C:CT	donor_loss	1.0000
20:32704900:TTCCA:T	acceptor_gain	1.0000
20:32704901:TCCA:T	acceptor_gain	1.0000
20:32704902:CCA:C	acceptor_gain	1.0000
20:32704902:CCAC:C	acceptor_gain	1.0000
20:32704903:CA:C	acceptor_gain	1.0000
20:32704903:CAC:C	acceptor_gain	1.0000
20:32704903:CACTG:C	acceptor_loss	1.0000
20:32704904:ACT:A	acceptor_loss	1.0000
20:32704905:C:CC	acceptor_gain	1.0000
20:32704905:CTGG:C	acceptor_loss	1.0000
20:32704906:T:C	acceptor_loss	1.0000
20:32704911:C:CT	acceptor_gain	1.0000
20:32704912:A:T	acceptor_gain	1.0000
20:32727889:TCA:T	donor_loss	1.0000
20:32727890:CACCA:C	donor_loss	1.0000
20:32727891:A:AC	donor_gain	1.0000
20:32727891:A:T	donor_loss	1.0000
20:32727891:AC:A	donor_gain	1.0000
20:32727892:C:CG	donor_gain	1.0000

AlphaMissense

1319 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:32704826:A:G	W139R	0.998
20:32704826:A:T	W139R	0.998
20:32704070:A:G	L160P	0.994
20:32704824:C:A	W139C	0.994
20:32704824:C:G	W139C	0.994
20:32703439:G:C	F182L	0.992
20:32703439:G:T	F182L	0.992
20:32703441:A:G	F182L	0.992
20:32704904:A:G	W113R	0.992
20:32704904:A:T	W113R	0.992
20:32704825:C:G	W139S	0.991
20:32703440:A:G	F182S	0.988
20:32704818:A:C	F141L	0.988
20:32704818:A:T	F141L	0.988
20:32704820:A:G	F141L	0.988
20:32703428:A:G	L186P	0.986
20:32704819:A:G	F141S	0.986
20:32704446:A:C	F157L	0.985
20:32704446:A:T	F157L	0.985
20:32704448:A:G	F157L	0.985
20:32703455:A:G	L177S	0.983
20:32706617:A:G	L101P	0.983
20:32704444:A:G	L158S	0.982
20:32703431:A:G	F185S	0.981
20:32704840:A:T	L134H	0.981
20:32706727:A:T	V92D	0.977
20:32704476:G:C	S147R	0.975
20:32704476:G:T	S147R	0.975
20:32704478:T:G	S147R	0.975
20:32727901:A:T	V78D	0.974

dbSNP variants (sampled 300 via entrez): RS1000129835 (20:32711901 T>C), RS1000154581 (20:32742002 A>G), RS1000239636 (20:32716523 G>A), RS1000270063 (20:32716389 G>C), RS1000314021 (20:32703712 T>C), RS1000468317 (20:32710024 A>G), RS1000478310 (20:32737212 A>G), RS1000485835 (20:32742130 T>C), RS1000501713 (20:32715427 G>A), RS1000574349 (20:32706075 G>A), RS1000608869 (20:32714924 C>T), RS1000611426 (20:32706505 T>A,C), RS1000729975 (20:32708932 A>C), RS1000780983 (20:32744342 T>C), RS1000785401 (20:32708600 A>G)

Disease associations

OMIM: gene MIM:616703 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002806_15	Type 2 diabetes	9.000000e-06
GCST005976_25	White blood cell count (basophil)	4.000000e-08
GCST008362_39	Birth weight	1.000000e-24
GCST008403_14	Arterial stiffness index	3.000000e-06
GCST008839_110	Height	6.000000e-09
GCST009391_173	Metabolite levels	7.000000e-07
GCST010135_49	Oily fish consumption	4.000000e-08
GCST010140_39	Pork consumption	4.000000e-08
GCST010703_192	Brain morphology (MOSTest)	8.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0004344	birth weight
EFO:0004517	arterial stiffness measurement
EFO:0010488	glycerol-3-phosphate measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cupric chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Smoke	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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