COMMD10

Summary

COMMD10 (COMM domain containing 10, HGNC:30201) is a protein-coding gene on chromosome 5q23.1, encoding COMM domain-containing protein 10 (Q9Y6G5). 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.

Located in nucleoplasm.

Source: NCBI Gene 51397 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_016144

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30201
Approved symbol	COMMD10
Name	COMM domain containing 10
Location	5q23.1
Locus type	gene with protein product
Status	Approved
Aliases	PTD002
Ensembl gene	ENSG00000145781
Ensembl biotype	protein_coding
OMIM	616704
Entrez	51397

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000274458, ENST00000503424, ENST00000506589, ENST00000507356, ENST00000508250, ENST00000515539, ENST00000632434, ENST00000908482

RefSeq mRNA: 2 — MANE Select: NM_016144 NM_001308080, NM_016144

CCDS: CCDS34215, CCDS78049

Canonical transcript exons

ENST00000274458 — 7 exons

Exon	Start	End
ENSE00000972237	116091079	116091189
ENSE00001005662	116092545	116092700
ENSE00001274247	116292451	116293287
ENSE00002029861	116085025	116085093
ENSE00003470480	116087497	116087587
ENSE00003537569	116291517	116291576
ENSE00003543802	116134068	116134178

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0947 / max 224.4737, expressed in 1801 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58075	21.4347	1801
203664	0.6448	426
58077	0.0152	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.80	gold quality
secondary oocyte	CL:0000655	98.38	gold quality
adrenal tissue	UBERON:0018303	93.66	gold quality
monocyte	CL:0000576	92.92	gold quality
mononuclear cell	CL:0000842	92.87	gold quality
leukocyte	CL:0000738	92.57	gold quality
buccal mucosa cell	CL:0002336	92.21	silver quality
ventricular zone	UBERON:0003053	92.05	gold quality
rectum	UBERON:0001052	91.08	gold quality
parotid gland	UBERON:0001831	91.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.86	gold quality
islet of Langerhans	UBERON:0000006	90.85	gold quality
right adrenal gland cortex	UBERON:0035827	90.76	gold quality
gall bladder	UBERON:0002110	90.49	gold quality
ganglionic eminence	UBERON:0004023	90.35	gold quality
heart left ventricle	UBERON:0002084	90.07	gold quality
right adrenal gland	UBERON:0001233	90.04	gold quality
right atrium auricular region	UBERON:0006631	90.03	gold quality
cardiac ventricle	UBERON:0002082	89.89	gold quality
left adrenal gland	UBERON:0001234	89.86	gold quality
heart	UBERON:0000948	89.64	gold quality
left adrenal gland cortex	UBERON:0035825	89.64	gold quality
adrenal gland	UBERON:0002369	89.62	gold quality
cardiac atrium	UBERON:0002081	89.56	gold quality
pigmented layer of retina	UBERON:0001782	89.48	gold quality
calcaneal tendon	UBERON:0003701	89.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.33	gold quality
bone marrow cell	CL:0002092	89.30	gold quality
left lobe of thyroid gland	UBERON:0001120	89.19	gold quality
embryo	UBERON:0000922	89.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting COMMD10, 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-126-5P	100.00	72.71	3180
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-132-3P	99.73	70.56	1424

Literature-anchored findings (GeneRIF, showing 5)

• Data demonstrate that the FMNL2/COMMD10/p65 NF kappaB axis acts as a critical regulator in the maintenance of metastatic phenotypes in colorectal cancer. (PMID:28817833)
• Expression profile and bioinformatics analysis of COMMD10 in BALB/C mice and human. (PMID:30787448)
• COMMD10 inhibits tumor progression and induces apoptosis by blocking NF-kappaB signal and values up BCLC staging in predicting overall survival in hepatocellular carcinoma. (PMID:34047468)
• COMMD10 inhibits HIF1alpha/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma. (PMID:35101526)
• Comprehensive analysis of COMMD10 as a novel prognostic biomarker for gastric cancer. (PMID:36919165)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Commd10	ENSMUSG00000042705
rattus_norvegicus	Commd10	ENSRNOG00000003958
drosophila_melanogaster	Vlet	FBGN0030323

Protein

Protein identifiers

COMM domain-containing protein 10 — Q9Y6G5 (reviewed: Q9Y6G5)

All UniProt accessions (4): D6RC04, D6RJ90, Q9Y6G5, H0Y9N4

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 COMMD5. Interacts with RELA, RELB, NFKB1/p105, NFKB2/p100. Interacts with CCDC22, CCDC93, SCNN1B, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL7.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the COMM domain-containing protein 10 family.

RefSeq proteins (2): NP_001295009, NP_057228* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017920	COMM	Domain
IPR037361	COMMD10	Family

Pfam: PF07258, PF21672

UniProt features (19 total): helix 7, strand 4, turn 2, modified residue 2, initiator methionine 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9ZMY	X-RAY DIFFRACTION	1.62
9ZN0	X-RAY DIFFRACTION	2.12
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-Q9Y6G5-F1	84.19	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 155

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 115 (showing top): YAATNRNNNYNATT_UNKNOWN, GOBP_VESICLE_MEDIATED_TRANSPORT, IRF7_01, OCT1_07, TGANTCA_AP1_C, GOBP_ENDOCYTIC_RECYCLING, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_LIVER_CANCER_UP, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, HOXA4_Q2, NKX3A_01, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, PARENT_MTOR_SIGNALING_UP

GO Biological Process (0):

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

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nucleus (GO:0005634)

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
cellular anatomical structure	2
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1129 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD10	COMMD9	Q9P000	774
COMMD10	COMMD2	Q86X83	743
COMMD10	COMMD5	Q9GZQ3	728
COMMD10	COMMD6	Q7Z4G1	718
COMMD10	A0A2R8Y455	A0A2R8Y455	714
COMMD10	COMMD1	Q8N668	714
COMMD10	COMMD7	Q86VX2	709
COMMD10	CCDC93	Q567U6	668
COMMD10	COMMD8	Q9NX08	636
COMMD10	COMMD3	Q9UBI1	626
COMMD10	CCDC22	O60826	590
COMMD10	COMMD4	Q9H0A8	571
COMMD10	VPS35L	Q7Z3J2	439
COMMD10	OR1L6	Q8NGR2	431
COMMD10	AP3S1	Q92572	426

IntAct

89 interactions, top by confidence:

A	B	Type	Score
CCDC22	COMMD1	psi-mi:“MI:0914”(association)	0.970
CCDC93	CCDC22	psi-mi:“MI:0914”(association)	0.960
CCDC22	CCDC93	psi-mi:“MI:0915”(physical association)	0.960
CCDC22	CCDC93	psi-mi:“MI:0914”(association)	0.960
COMMD6	COMMD1	psi-mi:“MI:0914”(association)	0.950
COMMD1	COMMD6	psi-mi:“MI:0915”(physical association)	0.950
COMMD9	CCDC22	psi-mi:“MI:0914”(association)	0.940
COMMD10	CCDC22	psi-mi:“MI:0914”(association)	0.940
COMMD10	CCDC22	psi-mi:“MI:0915”(physical association)	0.940
CCDC22	COMMD6	psi-mi:“MI:0914”(association)	0.930
COMMD6	CCDC22	psi-mi:“MI:0914”(association)	0.930
COMMD5	CCDC22	psi-mi:“MI:0914”(association)	0.930
COMMD5	COMMD10	psi-mi:“MI:0915”(physical association)	0.870
COMMD10	CCDC93	psi-mi:“MI:0915”(physical association)	0.850
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
COMMD1	COMMD10	psi-mi:“MI:0915”(physical association)	0.830
CCDC22	VPS26C	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
VPS35L	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730

BioGRID (105): COMMD10 (Affinity Capture-MS), COMMD10 (Affinity Capture-MS), CCDC22 (Co-fractionation), COMMD1 (Co-fractionation), COMMD10 (Co-fractionation), COMMD10 (Co-fractionation), COMMD2 (Co-fractionation), COMMD5 (Co-fractionation), COMMD10 (Affinity Capture-MS), COMMD10 (Affinity Capture-MS), COMMD10 (Affinity Capture-MS), COMMD8 (Affinity Capture-MS), COMMD10 (Affinity Capture-MS), COMMD3 (Affinity Capture-MS), COMMD2 (Affinity Capture-MS)

ESM2 similar proteins: A2AA28, A2RRH5, A2RT67, A2RUS2, B2RYG8, O09172, O75031, P0CL18, P11716, P41214, P48507, P48508, P48553, P50747, Q0IHA2, Q0PNE2, Q0V8R7, Q28CX0, Q2KHY5, Q2T9Y6, Q2TBH1, Q2TBN5, Q3SZD4, Q3T0J1, Q3TLI0, Q499N3, Q4VBE8, Q568M3, Q58CR3, Q5RA63, Q5RJL2, Q5TYQ1, Q6NYU2, Q8BK75, Q8BQX5, Q8CHQ0, Q8K2Q0, Q8VCX6, Q91W86, Q920N2

Diamond homologs: Q554G3, Q8JZY2, Q9Y6G5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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	15.8×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
Golgi to plasma membrane transport	5	72.0×	1e-06
endocytic recycling	6	41.1×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2192 predictions. Top by Δscore:

Variant	Effect	Δscore
5:116085091:CAGGT:C	donor_loss	1.0000
5:116085092:AGGTA:A	donor_loss	1.0000
5:116085106:T:G	donor_gain	1.0000
5:116085133:G:GT	donor_gain	1.0000
5:116087485:A:AG	acceptor_gain	1.0000
5:116087493:TTAGC:T	acceptor_loss	1.0000
5:116087494:TAGCA:T	acceptor_loss	1.0000
5:116087495:A:AG	acceptor_gain	1.0000
5:116087495:AGCA:A	acceptor_loss	1.0000
5:116087496:G:A	acceptor_loss	1.0000
5:116087496:G:GC	acceptor_gain	1.0000
5:116087496:GC:G	acceptor_gain	1.0000
5:116087496:GCAT:G	acceptor_gain	1.0000
5:116088598:G:GG	donor_gain	1.0000
5:116091073:TTATA:T	acceptor_loss	1.0000
5:116091074:TATA:T	acceptor_loss	1.0000
5:116091076:TAGGC:T	acceptor_loss	1.0000
5:116091077:A:AG	acceptor_gain	1.0000
5:116091077:AGGCT:A	acceptor_gain	1.0000
5:116091078:G:GA	acceptor_gain	1.0000
5:116091078:GGCT:G	acceptor_gain	1.0000
5:116091078:GGCTG:G	acceptor_gain	1.0000
5:116092540:A:AG	acceptor_gain	1.0000
5:116092540:AATAG:A	acceptor_gain	1.0000
5:116092541:A:G	acceptor_gain	1.0000
5:116092543:A:AG	acceptor_gain	1.0000
5:116092543:AG:A	acceptor_gain	1.0000
5:116092544:G:GA	acceptor_gain	1.0000
5:116092544:GG:G	acceptor_gain	1.0000
5:116092544:GGC:G	acceptor_gain	1.0000

AlphaMissense

1324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:116091116:T:C	L57P	0.993
5:116134083:T:A	W139R	0.993
5:116134083:T:C	W139R	0.993
5:116292473:T:C	L198P	0.992
5:116092638:T:A	W113R	0.991
5:116092638:T:C	W113R	0.991
5:116292452:T:C	L191P	0.989
5:116292461:T:A	I194K	0.988
5:116134096:T:C	L143P	0.987
5:116092545:G:C	A82P	0.986
5:116134090:T:C	L141P	0.985
5:116087553:T:C	L33S	0.983
5:116087562:G:C	R36P	0.983
5:116091091:T:C	F49L	0.979
5:116091093:C:A	F49L	0.979
5:116091093:C:G	F49L	0.979
5:116134141:C:A	A158D	0.979
5:116292461:T:G	I194R	0.979
5:116291557:T:C	L184S	0.977
5:116091116:T:A	L57H	0.976
5:116091092:T:C	F49S	0.975
5:116091149:T:C	L68P	0.975
5:116134147:T:C	L160S	0.973
5:116087556:T:C	L34P	0.972
5:116134140:G:C	A158P	0.972
5:116292465:A:C	Q195H	0.972
5:116292465:A:T	Q195H	0.972
5:116134153:T:C	L162P	0.971
5:116292482:T:C	L201P	0.967
5:116087520:T:A	I22K	0.961

dbSNP variants (sampled 300 via entrez): RS1000000549 (5:116268126 G>T), RS1000006695 (5:116206511 G>A), RS1000009248 (5:116239424 T>A), RS1000010141 (5:116175770 C>G), RS1000014795 (5:116118260 A>G,T), RS1000030727 (5:116195931 A>G), RS1000038822 (5:116255401 C>T), RS1000041991 (5:116207863 T>G), RS1000070742 (5:116122507 A>G), RS1000096483 (5:116113189 A>C,G), RS1000102901 (5:116134155 G>A,C,T), RS1000106158 (5:116109741 C>G), RS1000131381 (5:116140267 C>CTGTATATATGTCTATGCG), RS1000145000 (5:116151491 G>A), RS1000150521 (5:116269619 C>T)

Disease associations

OMIM: gene MIM:616704 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001371_17	Inflammatory biomarkers	7.000000e-07
GCST001567_10	Bipolar disorder and schizophrenia	8.000000e-06
GCST002119_5	Metabolite levels (X-11787)	4.000000e-06
GCST002519_2	Asthma or chronic obstructive pulmonary disease	4.000000e-06
GCST009136_1	Ankle-brachial index	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005276	hydroxy-leucine measurement
EFO:0003912	ankle brachial index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	4
sodium arsenite	decreases expression, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance, decreases reaction	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
ochratoxin A	decreases expression	1
cupric chloride	decreases expression	1
glycidamide	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	decreases expression, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Carcinogens	decreases expression	1
Coal	decreases expression, increases abundance	1
Dexamethasone	increases expression, affects cotreatment	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Mustard Gas	decreases expression	1
Mutagens	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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