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 and tumor necrosis factor-mediated signaling pathway. Part of protein-containing complex.

Source: NCBI Gene 149951 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 53 total
• GTEx eGene: eQTL in 37 tissues, sQTL in 23 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.15 (unconstrained)
• MANE Select transcript: NM_053041
• Notable: 53 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 42 — 25 protein_coding, 17 nonsense_mediated_decay

MANE Select: ENST00000278980

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

ENST00000278980, ENST00000446419, ENST00000474815, ENST00000610160, ENST00000855714, ENST00000855715, ENST00000855716, ENST00000855717, ENST00000855718, ENST00000855719, ENST00000855720, ENST00000855721, ENST00000934209, ENST00000941360, ENST00000941361, ENST00000989126, ENST00000989127, ENST00000989128, ENST00000989129, ENST00000989130, ENST00000989132, ENST00000989133, ENST00000989134, ENST00000989135, ENST00000989136, ENST00000989138, ENST00000989140, ENST00000989141, ENST00000989143, ENST00000989144, ENST00001025591, ENST00001025592, ENST00001025593, ENST00001025594, ENST00001025595, ENST00001025596, ENST00001106521, ENST00001118270, ENST00001118271, ENST00001127018, ENST00001127019, ENST00001131920

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.

Highest expression (Bgee): kidney epithelium, ventricle myocardium, middle temporal gyrus, upper arm skin, deltoid.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COMMD7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 23 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 60 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.4e-43	-0.31	20:32721251:T:C
Nerve Tibial	eqtl	6.3e-22	+0.25	20:32743524:A:G
Artery Tibial	eqtl	2.6e-21	+0.23	20:32742806:A:G
Thyroid	eqtl	5.0e-19	+0.24	20:32711057:G:A
Esophagus Muscularis	eqtl	7.6e-17	+0.26	20:32743524:A:G
Adipose Subcutaneous	eqtl	2.0e-16	-0.24	20:32741898:A:G
Colon Sigmoid	eqtl	7.0e-15	+0.22	20:32780754:T:C
Colon Transverse	eqtl	7.4e-15	+0.31	20:32788476:T:G
Testis	eqtl	5.2e-13	+0.22	20:32742607:G:A
Artery Aorta	eqtl	1.1e-12	+0.25	20:32742806:A:G
Esophagus Mucosa	eqtl	2.7e-11	+0.19	20:32747351:A:G
Nerve Tibial	sqtl	7.6e-11	+0.42	20:32703823:A:G
Artery Tibial	sqtl	1.9e-10	+0.42	20:32703823:A:G
Esophagus Gastroesophageal Junction	eqtl	3.4e-10	+0.23	20:32742806:A:G
Colon Sigmoid	sqtl	7.1e-10	+0.51	20:32651496:A:G
Lung	eqtl	1.9e-09	+0.24	20:32706978:A:G
Brain Cortex	eqtl	1.5e-08	+0.29	20:32743524:A:G
Brain Nucleus accumbens basal ganglia	sqtl	1.9e-07	-0.76	20:32739451:C:A
Brain Anterior cingulate cortex BA24	eqtl	2.3e-07	+0.26	20:32742309:C:T
Whole Blood	eqtl	2.5e-07	+0.15	20:32706978:A:G

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

showing 100 of 257 tissues 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
Brodmann (1909) area 23	UBERON:0013554	94.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.38	gold quality
endothelial cell	CL:0000115	94.36	gold quality
adult mammalian kidney	UBERON:0000082	94.35	gold quality
leukocyte	CL:0000738	94.30	gold quality
parietal pleura	UBERON:0002400	94.28	gold quality
ventricular zone	UBERON:0003053	94.25	gold quality
monocyte	CL:0000576	94.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.07	silver quality
right coronary artery	UBERON:0001625	94.02	gold quality
ganglionic eminence	UBERON:0004023	94.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.02	gold quality
lower esophagus	UBERON:0013473	94.00	gold quality
left coronary artery	UBERON:0001626	93.96	gold quality
heart	UBERON:0000948	93.93	gold quality
coronary artery	UBERON:0001621	93.91	gold quality
ascending aorta	UBERON:0001496	93.88	gold quality
neocortex	UBERON:0001950	93.88	gold quality
primary visual cortex	UBERON:0002436	93.88	gold quality
thoracic aorta	UBERON:0001515	93.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.85	gold quality
muscle tissue	UBERON:0002385	93.80	gold quality
skeletal muscle tissue	UBERON:0001134	93.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.77	gold quality
corpus epididymis	UBERON:0004359	93.71	gold quality
mucosa of transverse colon	UBERON:0004991	93.68	gold quality
cerebral cortex	UBERON:0000956	93.64	gold quality
caudate nucleus	UBERON:0001873	93.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.60	gold quality
palpebral conjunctiva	UBERON:0001812	93.59	gold quality
gastrocnemius	UBERON:0001388	93.55	gold quality
frontal cortex	UBERON:0001870	93.55	gold quality
nucleus accumbens	UBERON:0001882	93.53	gold quality
aorta	UBERON:0000947	93.52	gold quality
descending thoracic aorta	UBERON:0002345	93.52	gold quality
metanephros	UBERON:0000081	93.49	gold quality
prefrontal cortex	UBERON:0000451	93.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.40	gold quality
temporal lobe	UBERON:0001871	93.39	gold quality
right adrenal gland	UBERON:0001233	93.37	gold quality
metanephros cortex	UBERON:0010533	93.37	gold quality
right adrenal gland cortex	UBERON:0035827	93.37	gold quality
putamen	UBERON:0001874	93.35	gold quality
secondary oocyte	CL:0000655	93.34	gold quality
popliteal artery	UBERON:0002250	93.30	gold quality
tibial artery	UBERON:0007610	93.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.29	gold quality
cardiac atrium	UBERON:0002081	93.25	gold quality
hypothalamus	UBERON:0001898	93.24	gold quality
prostate gland	UBERON:0002367	93.24	gold quality
cortex of kidney	UBERON:0001225	93.23	gold quality
right atrium auricular region	UBERON:0006631	93.23	gold quality
colonic mucosa	UBERON:0000317	93.22	gold quality
smooth muscle tissue	UBERON:0001135	93.16	gold quality
cerebellar hemisphere	UBERON:0002245	93.16	gold quality
cerebellar cortex	UBERON:0002129	93.14	gold quality
muscle of leg	UBERON:0001383	93.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.08	gold quality
kidney	UBERON:0002113	93.04	gold quality
left adrenal gland	UBERON:0001234	92.93	gold quality
cerebellum	UBERON:0002037	92.88	gold quality
mammalian vulva	UBERON:0000997	92.87	gold quality
forebrain	UBERON:0001890	92.85	gold quality
left adrenal gland cortex	UBERON:0035825	92.82	gold quality
penis	UBERON:0000989	92.78	gold quality
body of stomach	UBERON:0001161	92.78	gold quality
body of pancreas	UBERON:0001150	92.74	gold quality
brain	UBERON:0000955	92.73	gold quality
adrenal cortex	UBERON:0001235	92.72	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Skeletal muscle	tissue	62.3
Tongue	tissue	50.8
Thyroid gland	tissue	46.6
Epididymis	tissue	46.3
Kidney	tissue	41.9
Superior colliculi	tissue	39.5
Thalamus	tissue	38.5
Parathyroid gland	tissue	38.3
Bone marrow	tissue	38.2
Pons	tissue	37.7
Placenta	tissue	36.2
Spinal cord	tissue	35.9
Liver	tissue	35.4
Heart muscle	tissue	35.3
Midbrain	tissue	35.0
Medulla oblongata	tissue	34.2
Substantia nigra	tissue	33.7
Urinary bladder	tissue	32.8
Corpus callosum	tissue	32.6
Hypothalamus	tissue	32.3
Breast	tissue	31.8
Tonsil	tissue	31.8
Cerebral cortex	tissue	31.7
Somatosensory cortex	tissue	31.7
Smooth muscle	tissue	31.0
Salivary gland	tissue	29.8
Colon	tissue	29.6
Periaqueductal gray	tissue	29.6
Occipital cortex	tissue	29.6
Seminal vesicle	tissue	29.4
Postcentral gyrus	tissue	29.2
Vagina	tissue	28.9
Locus coeruleus	tissue	28.7
Rectum	tissue	28.5
Pancreas	tissue	28.5
Lymph node	tissue	28.0
Septum	tissue	28.0
Cerebellum	tissue	27.6
Adipose tissue	tissue	27.5
Hippocampus	tissue	27.5
Prostate	tissue	27.5
Motor cortex	tissue	27.4
Nucleus accumbens	tissue	27.4
Choroid plexus	tissue	27.4
Hippocampal formation	tissue	27.4
Entorhinal cortex	tissue	26.6
Frontal cortex	tissue	26.4
Putamen	tissue	26.4
Lung	tissue	26.3
Skin 1	tissue	26.2
Temporal cortex	tissue	26.0
Olfactory bulb	tissue	25.9
Spleen	tissue	25.7
Fallopian tube	tissue	25.7
Ventral forebrain	tissue	24.9
Prefrontal cortex	tissue	24.8
Retrosplenial cortex	tissue	24.7
Ovary	tissue	24.6
Retrosplenial and cingulate cortex	tissue	24.4
Stomach 1	tissue	24.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (42.0), Periaquaductal grey, anterior (36.3), Ventral spinal cord (35.9), Posterior thalamic nucleus (34.9), Temporal pole (34.9).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting COMMD7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 34 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 8.69e-09, LOEUF 1.15, missense Z 0.59 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000278980 — one region, missense o/e 0.87.

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)

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	Q3MHX1	94.5%	Diamond
Dictyostelium discoideum	Q86I14	40.4%	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
NOL4L-DT	ncRNA	149950
C20orf203	protein-coding	284805
DNMT3B	protein-coding	1789
MAPRE1	protein-coding	22919
NOL4L-AS1	ncRNA	139355215
NOL4L	protein-coding	140688
EFCAB8	protein-coding	388795

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 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
8ESD	Crystal structure of COMMD7-COMMD9-COMMD5-COMMD10 tetramer	X-RAY DIFFRACTION	3.33
8F2U	Human CCC complex	ELECTRON MICROSCOPY	3.53

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IF approved

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: 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 (4): DNA-templated transcription (GO:0006351), endocytic recycling (GO:0032456), 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 (4): endosome membrane (GO:0010008), protein-containing complex (GO:0032991), endoplasmic reticulum membrane (GO:0005789), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

2 top-level categories:

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

GO top-level categories

20 GO namespaces:

Category	Terms
gene expression	1
RNA biosynthetic process	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
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
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular_component	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of DNA-templated transcription	BP	direct assay
tumor necrosis factor-mediated signaling pathway	BP	direct assay
protein-containing complex	CC	direct assay
NF-kappaB binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 782 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD7	IARS1	P41252	846
COMMD7	PNRC2	Q9NPJ4	830
COMMD7	COMMD9	Q9P000	767
COMMD7	COMMD10	Q9Y6G5	732
COMMD7	DCP1A	Q9NPI6	722
COMMD7	COMMD2	Q86X83	701
COMMD7	COMMD6	Q7Z4G1	663
COMMD7	UPF1	Q92900	661
COMMD7	COMMD5	Q9GZQ3	659
COMMD7	COMMD8	Q9NX08	643
COMMD7	COMMD1	Q8N668	635
COMMD7	COMMD3	Q9UBI1	634
COMMD7	COMMD4	Q9H0A8	630
COMMD7	CCDC93	Q567U6	540
COMMD7	CCDC22	O60826	506

IntAct

Human interaction partners of COMMD7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
CCDC22	physical association	0.890	1
COMMD1	physical association	0.770	1
COMMD5	physical association	0.680	2
CCDC93	physical association	0.670	1
COMMD10	association	0.530	1
VPS26C	association	0.530	1
CHRM3	physical association	0.370	1
NFKB1	association	0.350	1

BioGRID (57 interactions; top human partners by supporting records): COMMD1 (Co-fractionation; 6 records), CCDC22 (Affinity Capture-MS; 5 records), COMMD4 (Affinity Capture-MS; 5 records), COMMD3 (Affinity Capture-MS; 4 records), COMMD6 (Affinity Capture-Western; 4 records), CCDC93 (Affinity Capture-MS; 3 records), COMMD10 (Affinity Capture-MS; 3 records), COMMD2 (Affinity Capture-MS; 3 records), COMMD8 (Affinity Capture-MS; 3 records), VPS29 (Affinity Capture-MS; 3 records), FAM45A (Affinity Capture-MS; 2 records), C15orf59 (Affinity Capture-MS), CCDC114 (Affinity Capture-MS), CHRM3 (Two-hybrid), CHUK (Affinity Capture-Western)

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 COMMD7: 53 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 976):

Position(s)	Effect	Δscore	Sites
20:32704075	acceptor_gain	1.0000
20:32704812–32704813	donor_loss	1.0000	5
20:32704905–32704906	acceptor_loss	1.0000	6
20:32704912	acceptor_gain	1.0000
20:32727891–32727892	donor_loss	1.0000	4
20:32727996–32727997	acceptor_loss	1.0000	5
20:32728087–32728088	donor_loss	1.0000	3
20:32728143–32728144	acceptor_loss	1.0000	6
20:32743319	donor_gain	1.0000
20:32704021–32704022	donor_loss	0.9900	5

AlphaMissense

348 missense substitutions predicted likely pathogenic (of 1,319 scored), across 98 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
F182	8	0.938	0.992
F141	8	0.928	0.988
F185	8	0.866	0.981
D95	8	0.789	0.910
W139	7	0.984	0.998
W113	7	0.925	0.992
F157	7	0.896	0.985
E176	7	0.850	0.925
D136	7	0.805	0.935
M189	6	0.888	0.962
V143	6	0.820	0.964
E190	6	0.808	0.887
E188	6	0.782	0.898
M137	6	0.755	0.954
H187	6	0.682	0.851
F57	5	0.909	0.931
F30	5	0.903	0.952
G146	5	0.889	0.949
G142	5	0.858	0.967
G154	5	0.841	0.915

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.55e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000144

Disease associations

OMIM: gene MIM:616703 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST008362_22	Birth weight	1e-24
GCST010703_58	Brain morphology (MOSTest)	8e-11
GCST008839_60	Height	6e-9
GCST005976_25	White blood cell count (basophil)	4e-8
GCST010135_22	Oily fish consumption	4e-8
GCST010140_49	Pork consumption	4e-8
GCST009391_151	Metabolite levels	7e-7
GCST008403_14	Arterial stiffness index	3e-6
GCST002806_15	Type 2 diabetes	9e-6

EFO canonical traits (from GWAS)

6 canonical traits:

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 (CPIC guideline: no)

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	decreases expression, affects expression	3
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cupric chloride	decreases expression	1
CGP 52608	increases reaction, affects binding	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)

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