COMMD9

Summary

COMMD9 (COMM domain containing 9, HGNC:25014) is a protein-coding gene on chromosome 11p13, encoding COMM domain-containing protein 9 (Q9P000). 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 sodium ion transport. Predicted to act upstream of or within cholesterol homeostasis. Located in Golgi apparatus; cytosol; and nucleoplasm.

Source: NCBI Gene 29099 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total — 1 likely-pathogenic
• MANE Select transcript: NM_014186

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25014
Approved symbol	COMMD9
Name	COMM domain containing 9
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	HSPC166, FLJ31106
Ensembl gene	ENSG00000110442
Ensembl biotype	protein_coding
OMIM	612299
Entrez	29099

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000263401, ENST00000355500, ENST00000452374, ENST00000526789, ENST00000528608, ENST00000532705, ENST00000533308, ENST00000533643, ENST00000877672, ENST00000877673, ENST00000877674

RefSeq mRNA: 4 — MANE Select: NM_014186 NM_001101653, NM_001307932, NM_001307937, NM_014186

CCDS: CCDS44571, CCDS76395, CCDS7900

Canonical transcript exons

ENST00000263401 — 6 exons

Exon	Start	End
ENSE00001102153	36277089	36277123
ENSE00001185319	36272292	36274772
ENSE00002173283	36289362	36289424
ENSE00003507465	36278477	36278616
ENSE00003521595	36280712	36280837
ENSE00003532019	36276137	36276240

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.2925 / max 218.1665, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119387	52.1261	1825
119386	0.1665	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.57	gold quality
prefrontal cortex	UBERON:0000451	96.17	gold quality
monocyte	CL:0000576	96.14	gold quality
leukocyte	CL:0000738	96.12	gold quality
mononuclear cell	CL:0000842	96.07	gold quality
granulocyte	CL:0000094	95.93	gold quality
cortical plate	UBERON:0005343	95.73	gold quality
islet of Langerhans	UBERON:0000006	95.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.50	gold quality
anterior cingulate cortex	UBERON:0009835	94.34	gold quality
cingulate cortex	UBERON:0003027	94.32	gold quality
right adrenal gland	UBERON:0001233	94.21	gold quality
ganglionic eminence	UBERON:0004023	94.15	gold quality
right frontal lobe	UBERON:0002810	94.04	gold quality
spinal cord	UBERON:0002240	94.03	gold quality
right adrenal gland cortex	UBERON:0035827	94.01	gold quality
left adrenal gland	UBERON:0001234	93.96	gold quality
stromal cell of endometrium	CL:0002255	93.82	gold quality
gastrocnemius	UBERON:0001388	93.82	gold quality
muscle of leg	UBERON:0001383	93.75	gold quality
metanephros cortex	UBERON:0010533	93.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.69	gold quality
left adrenal gland cortex	UBERON:0035825	93.64	gold quality
amygdala	UBERON:0001876	93.51	gold quality
adrenal gland	UBERON:0002369	93.29	gold quality
frontal cortex	UBERON:0001870	93.27	gold quality
frontal lobe	UBERON:0016525	93.27	gold quality
adrenal cortex	UBERON:0001235	93.24	gold quality
neocortex	UBERON:0001950	93.24	gold quality
nucleus accumbens	UBERON:0001882	93.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.14
E-CURD-112	no	3.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting COMMD9, 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-4533	100.00	69.48	2758
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
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-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-7154-5P	99.69	70.52	1900

Literature-anchored findings (GeneRIF, showing 1)

• COMMD9 participates in TFDP1/E2F1 activation and plays a critical role in non-small cell lung cancer. (PMID:27871936)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	commd9	ENSDARG00000094258
mus_musculus	Commd9	ENSMUSG00000027163
rattus_norvegicus	Commd9	ENSRNOG00000004755

Protein

Protein identifiers

COMM domain-containing protein 9 — Q9P000 (reviewed: Q9P000)

All UniProt accessions (3): Q9P000, E9PJ95, Q53FR9

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. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits.

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 COMMD7. Interacts with RELB and NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL1.

Subcellular location. Nucleus. Cytoplasmic vesicle.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the COMM domain-containing protein 9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P000-1	1	yes
Q9P000-2	2

RefSeq proteins (4): NP_001095123, NP_001294861, NP_001294866, NP_054905* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017920	COMM	Domain
IPR037360	COMMD9	Family
IPR048676	COMMD9_N	Domain

Pfam: PF07258, PF20923

UniProt features (20 total): helix 10, strand 3, sequence conflict 2, initiator methionine 1, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4OE9	X-RAY DIFFRACTION	1.55
6BP6	X-RAY DIFFRACTION	2.17
4NKN	X-RAY DIFFRACTION	2.79
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-Q9P000-F1	85.27	0.36

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-8951664	Neddylation

MSigDB gene sets: 158 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD11B_DC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GCM_GSPT1, GOBP_STEROL_HOMEOSTASIS, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_MEDIATED_TRANSPORT, GCM_BCL2L1, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_LIPID_HOMEOSTASIS, GCM_NUMA1, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_ENDOCYTIC_RECYCLING, GCM_NF2, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (3): sodium ion transport (GO:0006814), cholesterol homeostasis (GO:0042632), monoatomic ion transport (GO:0006811)

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

GO Cellular Component (8): extracellular region (GO:0005576), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813), nucleus (GO:0005634), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
intracellular membrane-bounded organelle	2
metal ion transport	1
sterol homeostasis	1
transport	1
binding	1
nuclear lumen	1
endomembrane system	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular vesicle	1

Protein interactions and networks

STRING

1213 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD9	FJX1	Q86VR8	920
COMMD9	CCDC93	Q567U6	834
COMMD9	COMMD6	Q7Z4G1	780
COMMD9	COMMD5	Q9GZQ3	774
COMMD9	COMMD10	Q9Y6G5	774
COMMD9	COMMD4	Q9H0A8	760
COMMD9	COMMD2	Q86X83	747
COMMD9	COMMD1	Q8N668	733
COMMD9	A0A2R8Y455	A0A2R8Y455	715
COMMD9	TFDP1	Q14186	712
COMMD9	COMMD7	Q86VX2	711
COMMD9	COMMD8	Q9NX08	706
COMMD9	VPS35L	Q7Z3J2	687
COMMD9	CCDC22	O60826	677
COMMD9	COMMD3	Q9UBI1	665

IntAct

102 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
COMMD9	CCDC22	psi-mi:“MI:0914”(association)	0.940
COMMD10	CCDC22	psi-mi:“MI:0914”(association)	0.940
CCDC22	COMMD9	psi-mi:“MI:0915”(physical association)	0.940
CCDC22	COMMD6	psi-mi:“MI:0914”(association)	0.930
COMMD2	CCDC22	psi-mi:“MI:0914”(association)	0.930
COMMD5	CCDC22	psi-mi:“MI:0914”(association)	0.930
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
COMMD6	COMMD9	psi-mi:“MI:0915”(physical association)	0.840
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
VPS26C	CCDC22	psi-mi:“MI:0914”(association)	0.790
DENND10	CCDC93	psi-mi:“MI:0914”(association)	0.770
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
COMMD9	CCDC93	psi-mi:“MI:0915”(physical association)	0.740
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730

BioGRID (77): COMMD9 (Affinity Capture-RNA), COMMD9 (Affinity Capture-RNA), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD3 (Co-fractionation), COMMD6 (Co-fractionation), XPO7 (Co-fractionation), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS), COMMD9 (Affinity Capture-MS)

ESM2 similar proteins: A2A825, A4FVI0, E1C6Q1, E9PTA2, O15315, O35719, O43502, O54804, O95059, O95803, P22339, P47802, Q01134, Q19AV6, Q33DR3, Q3U129, Q3U2J5, Q3UFY7, Q3ZBL5, Q4R7M4, Q5BIM1, Q5PPH0, Q5R812, Q5RB79, Q5VYX0, Q5ZJB7, Q6DC64, Q6GV29, Q6P4H8, Q7Z624, Q80ZQ9, Q86YH6, Q8CIW5, Q8NBA8, Q8R1C6, Q8R2J9, Q91YD4, Q924H5, Q96IK5, Q96RR1

Diamond homologs: Q2TBN5, Q8K2Q0, Q9P000

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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	11.8×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
Golgi to plasma membrane transport	5	55.1×	5e-06
endocytic recycling	7	36.7×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	21
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
149701	GRCh38/hg38 11p13-12(chr11:36007377-40318124)x1	Likely pathogenic

SpliceAI

862 predictions. Top by Δscore:

Variant	Effect	Δscore
11:36274769:GGAT:G	acceptor_gain	1.0000
11:36274772:TCTGA:T	acceptor_loss	1.0000
11:36274773:C:CC	acceptor_gain	1.0000
11:36274773:C:CG	acceptor_loss	1.0000
11:36274774:T:G	acceptor_loss	1.0000
11:36274779:C:CT	acceptor_gain	1.0000
11:36276132:TGTAC:T	donor_loss	1.0000
11:36276133:GTAC:G	donor_loss	1.0000
11:36276134:TACCT:T	donor_loss	1.0000
11:36276135:AC:A	donor_loss	1.0000
11:36276136:C:CG	donor_loss	1.0000
11:36276237:GAGA:G	acceptor_gain	1.0000
11:36276237:GAGAC:G	acceptor_loss	1.0000
11:36276238:AGA:A	acceptor_gain	1.0000
11:36276238:AGACT:A	acceptor_loss	1.0000
11:36276239:GA:G	acceptor_gain	1.0000
11:36276240:ACTGT:A	acceptor_loss	1.0000
11:36276241:C:CC	acceptor_gain	1.0000
11:36276241:CTGT:C	acceptor_loss	1.0000
11:36276242:T:G	acceptor_loss	1.0000
11:36277087:A:AC	donor_gain	1.0000
11:36277088:C:CC	donor_gain	1.0000
11:36277088:CT:C	donor_gain	1.0000
11:36278471:ACTT:A	donor_loss	1.0000
11:36278472:CTTA:C	donor_loss	1.0000
11:36278473:TTACA:T	donor_loss	1.0000
11:36278474:T:TG	donor_loss	1.0000
11:36278475:A:AC	donor_gain	1.0000
11:36278475:A:AG	donor_loss	1.0000
11:36278476:C:CT	donor_gain	1.0000

AlphaMissense

1280 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:36276211:A:G	W128R	0.994
11:36276211:A:T	W128R	0.994
11:36280818:A:T	V24D	0.992
11:36274666:A:G	I188T	0.990
11:36274663:C:G	R189P	0.989
11:36274711:A:G	L173P	0.989
11:36278504:A:G	L97P	0.989
11:36277116:A:G	W109R	0.988
11:36277116:A:T	W109R	0.988
11:36276154:A:G	C147R	0.987
11:36274666:A:C	I188S	0.985
11:36274696:A:G	L178P	0.985
11:36274666:A:T	I188N	0.984
11:36278513:A:G	L94P	0.984
11:36274654:A:G	L192P	0.983
11:36278501:A:G	L98P	0.982
11:36280826:T:A	K21N	0.979
11:36280826:T:G	K21N	0.979
11:36274675:A:G	L185P	0.977
11:36276147:A:G	L149P	0.977
11:36280807:A:G	C28R	0.977
11:36280827:T:A	K21I	0.976
11:36276150:A:G	L148P	0.974
11:36276152:G:C	C147W	0.973
11:36274669:C:G	R187P	0.969
11:36278501:A:C	L98R	0.966
11:36274654:A:T	L192H	0.965
11:36278603:A:G	L64P	0.964
11:36274687:A:T	M181K	0.961
11:36280836:G:T	A18D	0.959

dbSNP variants (sampled 300 via entrez): RS1000030753 (11:36289991 T>G), RS1000092366 (11:36283366 T>C), RS1000383354 (11:36280332 C>T), RS1000447611 (11:36287792 A>T), RS1000552918 (11:36273761 G>A), RS1000735477 (11:36288146 C>G,T), RS1000850567 (11:36281976 A>C), RS1000948924 (11:36275403 C>T), RS1000980098 (11:36275604 C>T), RS1001105546 (11:36281634 G>A), RS1001153700 (11:36273967 T>C), RS1001278745 (11:36282829 A>T), RS1001465768 (11:36289576 A>G), RS1001647795 (11:36282629 G>A,T), RS1001667241 (11:36276002 C>A,T)

Disease associations

OMIM: gene MIM:612299 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009379_217	Type 2 diabetes	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Air Pollutants	affects expression, increases abundance, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1
Diethylstilbestrol	decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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