COMMD4

Summary

COMMD4 (COMM domain containing 4, HGNC:26027) is a protein-coding gene on chromosome 15q24.2, encoding COMM domain-containing protein 4 (Q9H0A8). 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 signal transduction. Located in cytosol. Part of protein-containing complex.

Source: NCBI Gene 54939 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 52 total — 1 pathogenic
• GTEx eGene: eQTL in 44 tissues, sQTL in 42 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• MANE Select transcript: NM_017828
• Notable: 52 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26027
Approved symbol	COMMD4
Name	COMM domain containing 4
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20452
Ensembl gene	ENSG00000140365
Ensembl biotype	protein_coding
OMIM	616701
Entrez	54939

Gene structure

Transcript identifiers

Ensembl transcripts: 69 — 38 protein_coding, 16 nonsense_mediated_decay, 14 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000267935

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 9, TSL 3: 7, TSL 4: 2, TSL 5: 4

ENST00000267935, ENST00000338995, ENST00000480484, ENST00000561662, ENST00000562310, ENST00000562610, ENST00000562789, ENST00000563220, ENST00000564068, ENST00000564587, ENST00000564815, ENST00000565517, ENST00000565834, ENST00000566230, ENST00000566843, ENST00000567023, ENST00000567195, ENST00000567377, ENST00000567399, ENST00000567720, ENST00000567935, ENST00000568034, ENST00000568301, ENST00000568877, ENST00000569245, ENST00000869634, ENST00000869635, ENST00000869636, ENST00000869637, ENST00000869638, ENST00000869639, ENST00000869640, ENST00000869641, ENST00000928185, ENST00000928186, ENST00000928187, ENST00000928188, ENST00000928189, ENST00000928190, ENST00000928191, ENST00000928192, ENST00000928193, ENST00000928194, ENST00000928195, ENST00000944821, ENST00000944822, ENST00000985944, ENST00000985945, ENST00000985946, ENST00001053198, ENST00001053199, ENST00001053200, ENST00001064484, ENST00001064490, ENST00001092557, ENST00001092558, ENST00001092559, ENST00001092560, ENST00001092561, ENST00001092562, ENST00001092563, ENST00001092564, ENST00001092565, ENST00001092566, ENST00001092567, ENST00001092568, ENST00001092569, ENST00001092570, ENST00001136376

RefSeq mRNA: 9 — MANE Select: NM_017828 NM_001284377, NM_001284378, NM_001284379, NM_001321844, NM_001321845, NM_001321846, NM_001321847, NM_001321848, NM_017828

CCDS: CCDS10277, CCDS66834, CCDS66835, CCDS73764, CCDS81909

Canonical transcript exons

ENST00000267935 — 8 exons

Exon	Start	End
ENSE00001424829	75336063	75336092
ENSE00001842777	75339965	75340273
ENSE00003463152	75339264	75339344
ENSE00003533754	75338355	75338420
ENSE00003552441	75339702	75339878
ENSE00003574027	75338646	75338685
ENSE00003585450	75338985	75339104
ENSE00003619772	75338062	75338133

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0299 / max 69.9234, expressed in 1778 samples.

Highest expression (Bgee): testis, adrenal gland, adrenal gland cortex, adrenal cortex, granulocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COMMD4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 42 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 86 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	2.6e-34	-0.77	15:75336073:C:T
Esophagus Muscularis	eqtl	5.3e-34	-0.81	15:75336073:C:T
Cells Cultured fibroblasts	sqtl	1.1e-32	-0.72	15:75338294:A:T
Adipose Subcutaneous	eqtl	2.2e-32	-0.76	15:75336073:C:T
Artery Tibial	eqtl	1.1e-30	-0.65	15:75336073:C:T
Nerve Tibial	eqtl	3.6e-28	-0.61	15:75336073:C:T
Skin Not Sun Exposed Suprapubic	eqtl	6.8e-27	-0.69	15:75336073:C:T
Skin Sun Exposed Lower leg	eqtl	5.0e-25	-0.64	15:75336073:C:T
Muscle Skeletal	eqtl	2.6e-24	-0.57	15:75336073:C:T
Lung	eqtl	2.0e-23	-0.44	15:75336073:C:T
Artery Aorta	eqtl	2.1e-23	-0.63	15:75336073:C:T
Heart Atrial Appendage	eqtl	3.3e-20	-0.67	15:75336073:C:T
Breast Mammary Tissue	eqtl	1.8e-19	-0.62	15:75336073:C:T
Testis	sqtl	2.5e-19	-0.54	15:75316689:A:C
Brain Cortex	eqtl	7.4e-19	-0.86	15:75336073:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.6e-18	-0.79	15:75336073:C:T
Esophagus Gastroesophageal Junction	eqtl	1.4e-16	-0.61	15:75336073:C:T
Colon Sigmoid	eqtl	9.7e-16	-0.69	15:75336073:C:T
Adipose Visceral Omentum	eqtl	1.3e-15	-0.55	15:75336073:C:T
Heart Left Ventricle	eqtl	2.2e-15	-0.64	15:75336073:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
147798	9.2129	1751
147797	1.0864	763
147799	0.7307	434

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.71	gold quality
right testis	UBERON:0004534	97.59	gold quality
right adrenal gland	UBERON:0001233	97.45	gold quality
right adrenal gland cortex	UBERON:0035827	97.41	gold quality
left adrenal gland cortex	UBERON:0035825	97.24	gold quality
left adrenal gland	UBERON:0001234	97.13	gold quality
adrenal cortex	UBERON:0001235	96.89	gold quality
granulocyte	CL:0000094	96.66	gold quality
mucosa of transverse colon	UBERON:0004991	96.16	gold quality
metanephros cortex	UBERON:0010533	96.13	gold quality
apex of heart	UBERON:0002098	95.88	gold quality
adrenal gland	UBERON:0002369	95.73	gold quality
stromal cell of endometrium	CL:0002255	95.51	gold quality
testis	UBERON:0000473	95.47	gold quality
body of stomach	UBERON:0001161	95.40	gold quality
right lobe of thyroid gland	UBERON:0001119	95.11	gold quality
adenohypophysis	UBERON:0002196	95.07	gold quality
left lobe of thyroid gland	UBERON:0001120	95.01	gold quality
transverse colon	UBERON:0001157	94.70	gold quality
minor salivary gland	UBERON:0001830	94.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.57	gold quality
right lobe of liver	UBERON:0001114	94.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.51	gold quality
mucosa of stomach	UBERON:0001199	94.43	gold quality
endometrium epithelium	UBERON:0004811	94.42	gold quality
right uterine tube	UBERON:0001302	94.40	gold quality
ectocervix	UBERON:0012249	94.38	gold quality
lower esophagus	UBERON:0013473	94.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.36	gold quality
left coronary artery	UBERON:0001626	94.34	gold quality
pituitary gland	UBERON:0000007	94.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.24	gold quality
gall bladder	UBERON:0002110	94.23	gold quality
thyroid gland	UBERON:0002046	94.21	gold quality
body of uterus	UBERON:0009853	94.21	gold quality
ganglionic eminence	UBERON:0004023	94.19	gold quality
endocervix	UBERON:0000458	94.15	gold quality
coronary artery	UBERON:0001621	94.06	gold quality
tibial nerve	UBERON:0001323	94.01	gold quality
spleen	UBERON:0002106	94.01	gold quality
right lung	UBERON:0002167	93.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.85	gold quality
embryo	UBERON:0000922	93.84	gold quality
left uterine tube	UBERON:0001303	93.82	gold quality
skin of leg	UBERON:0001511	93.80	gold quality
mouth mucosa	UBERON:0003729	93.79	gold quality
upper lobe of left lung	UBERON:0008952	93.75	gold quality
stomach	UBERON:0000945	93.73	gold quality
putamen	UBERON:0001874	93.72	gold quality
esophagus	UBERON:0001043	93.69	gold quality
right coronary artery	UBERON:0001625	93.68	gold quality
thymus	UBERON:0002370	93.68	gold quality
skin of abdomen	UBERON:0001416	93.66	gold quality
ventricular zone	UBERON:0003053	93.64	gold quality
body of pancreas	UBERON:0001150	93.63	gold quality
spinal cord	UBERON:0002240	93.62	gold quality
small intestine	UBERON:0002108	93.57	gold quality
omental fat pad	UBERON:0010414	93.47	gold quality
peritoneum	UBERON:0002358	93.45	gold quality
upper lobe of lung	UBERON:0008948	93.42	gold quality
lower esophagus mucosa	UBERON:0035834	93.38	gold quality
rectum	UBERON:0001052	93.37	gold quality
right ovary	UBERON:0002118	93.33	gold quality
popliteal artery	UBERON:0002250	93.32	gold quality
tibial artery	UBERON:0007610	93.32	gold quality
thoracic aorta	UBERON:0001515	93.30	gold quality
esophagus mucosa	UBERON:0002469	93.30	gold quality
ascending aorta	UBERON:0001496	93.28	gold quality
aorta	UBERON:0000947	93.27	gold quality
amygdala	UBERON:0001876	93.25	gold quality
descending thoracic aorta	UBERON:0002345	93.20	gold quality
nucleus accumbens	UBERON:0001882	93.15	gold quality
lymph node	UBERON:0000029	93.13	gold quality
right frontal lobe	UBERON:0002810	93.08	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.02	gold quality
left ovary	UBERON:0002119	93.00	gold quality
right atrium auricular region	UBERON:0006631	92.86	gold quality
colon	UBERON:0001155	92.72	gold quality
smooth muscle tissue	UBERON:0001135	92.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.69	gold quality
sigmoid colon	UBERON:0001159	92.60	gold quality
large intestine	UBERON:0000059	92.57	gold quality
intestine	UBERON:0000160	92.56	gold quality
fundus of stomach	UBERON:0001160	92.55	gold quality
caudate nucleus	UBERON:0001873	92.54	gold quality
saliva-secreting gland	UBERON:0001044	92.50	gold quality
heart left ventricle	UBERON:0002084	92.45	gold quality
adult mammalian kidney	UBERON:0000082	92.29	gold quality
type B pancreatic cell	CL:0000169	92.23	silver quality
zone of skin	UBERON:0000014	92.22	gold quality
cingulate cortex	UBERON:0003027	92.22	gold quality
cardiac ventricle	UBERON:0002082	92.14	gold quality
anterior cingulate cortex	UBERON:0009835	92.08	gold quality
cardiac atrium	UBERON:0002081	92.07	gold quality
pancreas	UBERON:0001264	91.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.96	gold quality
olfactory bulb	UBERON:0002264	91.96	silver quality
vermiform appendix	UBERON:0001154	91.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	289.70
E-ANND-3	yes	8.08

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	59.9
Caudate putamen	tissue	52.5
Adrenal gland	tissue	52.0	not detected
Bone marrow	tissue	50.3	medium
Thymus	tissue	49.8
Parathyroid gland	tissue	46.0	medium
Testis	tissue	45.9	not detected
Duodenum	tissue	45.5	medium
Pituitary gland	tissue	45.3
Lymph node	tissue	42.2	not detected
Liver	tissue	41.6	low
Salivary gland	tissue	40.9	low
Small intestine	tissue	39.8	medium
Vagina	tissue	39.5	not detected
Colon	tissue	39.1	low
Heart muscle	tissue	36.7	medium
Thyroid gland	tissue	36.3	low
Stomach 1	tissue	36.1	medium
Gallbladder	tissue	35.0	low
Tonsil	tissue	34.9	not detected
Esophagus	tissue	34.3	not detected
Kidney	tissue	34.1	medium
Skin 1	tissue	33.2	low
Fallopian tube	tissue	32.7	not detected
Pancreas	tissue	32.5	not detected
Seminal vesicle	tissue	32.1	medium
Thalamus	tissue	31.9
Rectum	tissue	31.8	medium
Appendix	tissue	31.8	low
Ovary	tissue	31.6	low
Adipose tissue	tissue	31.3	medium
Pons	tissue	31.2
Urinary bladder	tissue	31.0	not detected
Midbrain	tissue	30.9
Superior colliculi	tissue	30.7
Spleen	tissue	30.7	not detected
Substantia nigra	tissue	30.6
Medulla oblongata	tissue	30.3
Spinal cord	tissue	30.3
Breast	tissue	30.1	medium
Lung	tissue	30.1	medium
Placenta	tissue	29.4	not detected
Cervix	tissue	29.2	not detected
Corpus callosum	tissue	29.0
Epididymis	tissue	28.6	not detected
Putamen	tissue	28.2
Hippocampal formation	tissue	27.7
Entorhinal cortex	tissue	27.5
Prefrontal cortex	tissue	27.3
Cerebral cortex	tissue	27.3	low
Somatosensory cortex	tissue	27.1
Motor cortex	tissue	26.7
Occipital cortex	tissue	26.7
Hypothalamus	tissue	26.4
Prostate	tissue	26.3	not detected
Temporal cortex	tissue	26.3
Septum	tissue	25.5
Choroid plexus	tissue	25.2
Cerebellum	tissue	24.8	low
Retrosplenial and cingulate cortex	tissue	24.8

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (41.6), Ventral spinal cord (30.3), Dorsal spinal cord (29.6), White matter (29.0), Dorsal hippocampus (27.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COMMD4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

9 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-2278	97.30	66.19	1130

Functional genomics

gnomAD constraint: pLI 9.61e-05, LOEUF 0.982, missense Z 0.12 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000267935 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 2)

• Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer. (PMID:32439936)
• COMMD4 functions with the histone H2A-H2B dimer for the timely repair of DNA double-strand breaks. (PMID:33875784)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	commd4	ENSDARG00000061946
mus_musculus	Commd4	ENSMUSG00000032299
rattus_norvegicus	Commd4	ENSRNOG00000018671
drosophila_melanogaster	CG34039	FBGN0054039
caenorhabditis_elegans	T28F2.2	WBGENE00020901

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	Q5E9V6	89.9%	Diamond
Dictyostelium discoideum	Q550I8	40.0%	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
SIN3A	protein-coding	25942
MAN2C1	protein-coding	4123
PTPN9	protein-coding	5780
MIR631	ncRNA	693216
NEIL1	protein-coding	79661
GOLGA6D	protein-coding	653643
GOLGA6C	protein-coding	653641

Protein

Protein identifiers

COMM domain-containing protein 4 — Q9H0A8 (reviewed: Q9H0A8)

All UniProt accessions (7): A0A0B4J287, Q9H0A8, H3BM91, H3BPG2, H3BQF2, H3BRX0, H3BTV9

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. Down-regulates 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 COMMD8. Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL2, CUL3, CUL4A, CUL5, CUL7.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the COMM domain-containing protein 4 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H0A8-1	1	yes
Q9H0A8-2	2
Q9H0A8-3	3

RefSeq proteins (9): NP_001271306, NP_001271307, NP_001271308, NP_001308773, NP_001308774, NP_001308775, NP_001308776, NP_001308777, NP_060298* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017920	COMM	Domain
IPR037356	COMMD4	Family
IPR047155	COMMD4/6/7/8	Family

Pfam: PF07258, PF21672

UniProt features (17 total): helix 9, strand 3, splice variant 2, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
9ZMZ	Crystal structure of the human Commd4 HN domain in a domain swapped conformation	X-RAY DIFFRACTION	2.12
8P0W	Structure of the human Commander complex COMMD ring	ELECTRON MICROSCOPY	2.9
8F2R	Human CCC complex	ELECTRON MICROSCOPY	3.12
8F2U	Human CCC complex	ELECTRON MICROSCOPY	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0A8-F1	80.85	0.08

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane; vesicles

Antibody reliability (HPA): IH uncertain · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-8951664	Neddylation	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 141 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ENDOCYTIC_RECYCLING, BASAKI_YBX1_TARGETS_UP, GOBP_LOCALIZATION_WITHIN_MEMBRANE, NUYTTEN_EZH2_TARGETS_DN, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, GOCC_MEMBRANE_PROTEIN_COMPLEX, MORF_RAN, MULLIGHAN_MLL_SIGNATURE_1_UP, MORF_CSNK2B, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, MORF_PSMC1, MORF_G22P1, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (3): DNA-templated transcription (GO:0006351), signal transduction (GO:0007165), endocytic recycling (GO:0032456)

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

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), endosome membrane (GO:0010008), protein-containing complex (GO:0032991), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

2 top-level categories:

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

GO top-level categories

21 GO namespaces:

Category	Terms
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	direct assay
cytosol	CC	direct assay
protein-containing complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,620 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMMD4	COMMD2	Q86X83	814
COMMD4	COMMD5	Q9GZQ3	803
COMMD4	COMMD8	Q9NX08	773
COMMD4	COMMD3	Q9UBI1	771
COMMD4	COMMD9	Q9P000	760
COMMD4	COMMD6	Q7Z4G1	713
COMMD4	CCDC22	O60826	678
COMMD4	COMMD1	Q8N668	678
COMMD4	COMMD10	Q9Y6G5	672
COMMD4	CCDC93	Q567U6	668
COMMD4	A0A2R8Y455	A0A2R8Y455	632
COMMD4	COMMD7	Q86VX2	630
COMMD4	DENND10	Q8TCE6	630
COMMD4	VPS35L	Q7Z3J2	626
COMMD4	VPS26C	O14972	545

IntAct

Human interaction partners of COMMD4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
CCDC22	physical association	0.920	1
COMMD1	physical association	0.920	1
COMMD8	physical association	0.880	9
COMMD2	physical association	0.820	1
CCDC93	physical association	0.800	1
VPS26C	association	0.730	3
PDE4DIP	physical association	0.540	4
BUB1B	physical association	0.370	1
BACH1	association	0.350	1
NFKB1	association	0.350	1
RPSA2	association	0.350	1

BioGRID (200 interactions; top human partners by supporting records): CCDC22 (Affinity Capture-MS; 7 records), COMMD1 (Affinity Capture-MS; 7 records), COMMD6 (Affinity Capture-MS; 7 records), CCDC93 (Affinity Capture-MS; 6 records), COMMD2 (Affinity Capture-MS; 6 records), COMMD10 (Affinity Capture-MS; 5 records), COMMD5 (Affinity Capture-MS; 5 records), COMMD7 (Affinity Capture-MS; 5 records), COMMD8 (Affinity Capture-MS; 5 records), DSCR3 (Affinity Capture-MS; 5 records), VPS29 (Affinity Capture-MS; 5 records), C16orf62 (Affinity Capture-MS; 4 records), COMMD3 (Affinity Capture-MS; 4 records), COMMD9 (Affinity Capture-MS; 4 records), E2F6 (Affinity Capture-MS; 4 records)

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 COMMD4: 52 ClinVar records (1 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
58080	GRCh38/hg38 15q24.2(chr15:75336215-75658670)x3	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore COMMD4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 812):

Position(s)	Effect	Δscore	Sites
15:75338135	donor_gain	1.0000
15:75339345–75339346	donor_loss	1.0000	5
15:75338060–75338061	acceptor_loss	0.9900	6
15:75338131	donor_gain	0.9900
15:75338148	donor_gain	0.9900
15:75338686–75338687	donor_loss	0.9900	5
15:75338974	acceptor_gain	0.9900
15:75339105–75339106	donor_loss	0.9900	5
15:75339201	acceptor_gain	0.9900
15:75338421–75338422	donor_loss	0.9800	4

AlphaMissense

451 missense substitutions predicted likely pathogenic (of 1,283 scored), across 129 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
F3	8	0.979	0.999
D10	8	0.972	0.989
F5	8	0.957	0.995
D13	8	0.937	0.983
W14	7	0.994	0.999
E92	7	0.977	0.992
C11	7	0.968	0.995
C6	7	0.937	0.982
Q95	7	0.924	0.987
F74	7	0.910	0.979
W136	7	0.881	0.988
E101	7	0.874	0.960
E18	7	0.850	0.978
G97	6	0.985	0.995
G7	6	0.967	0.993
P12	6	0.953	0.987
R2	6	0.952	0.976
K29	6	0.928	0.975
P99	6	0.881	0.947
H102	6	0.839	0.926

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	8.69e-05

Disease associations

OMIM: gene MIM:616701 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST008790_51	Urinary albumin-to-creatinine ratio	4e-16
GCST008972_115	Urate levels	3e-12
GCST007725_28	Serum uric acid levels	1e-8
GCST008791_25	Microalbuminuria	2e-7
GCST008971_6	Urate levels	2e-7
GCST008972_243	Urate levels	3e-7

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
cobaltous chloride	decreases expression	2
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
lasiocarpine	increases expression	1
bisphenol A	affects expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cypermethrin	increases expression	1
tetrabromobisphenol A	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Arsenic	increases abundance, increases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1

Clinical trials (associated diseases)

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