CMC2

Summary

CMC2 (C-X9-C motif containing 2, HGNC:24447) is a protein-coding gene on chromosome 16q23.2, encoding COX assembly mitochondrial protein 2 homolog (Q9NRP2). May be involved in cytochrome c oxidase biogenesis.

Located in cytosol and mitochondrion.

Source: NCBI Gene 56942 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_020188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24447
Approved symbol	CMC2
Name	C-X9-C motif containing 2
Location	16q23.2
Locus type	gene with protein product
Status	Approved
Aliases	DC13, MGC45036
Ensembl gene	ENSG00000103121
Ensembl biotype	protein_coding
Entrez	56942

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 19 protein_coding, 5 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000219400, ENST00000486645, ENST00000561614, ENST00000562713, ENST00000562828, ENST00000563779, ENST00000564174, ENST00000564249, ENST00000565108, ENST00000565514, ENST00000565613, ENST00000565650, ENST00000565914, ENST00000565925, ENST00000566047, ENST00000566231, ENST00000566918, ENST00000567593, ENST00000568228, ENST00000569187, ENST00000569666, ENST00000570086, ENST00000570195, ENST00000630396, ENST00000869353, ENST00000869354, ENST00000869355, ENST00000869356, ENST00000869357, ENST00000915514, ENST00000958083, ENST00000958084

RefSeq mRNA: 5 — MANE Select: NM_020188 NM_001351967, NM_001351968, NM_001351970, NM_001351973, NM_020188

CCDS: CCDS10930

Canonical transcript exons

ENST00000219400 — 4 exons

Exon	Start	End
ENSE00001922398	81006734	81006885
ENSE00003516882	80981806	80981877
ENSE00003568768	80997314	80997429
ENSE00003620751	80966448	80976179

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.7045 / max 288.0773, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158267	33.8301	1822
158266	0.4164	178
158263	0.2027	76
158264	0.1457	63
158268	0.0860	23
158265	0.0237	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.81	gold quality
oocyte	CL:0000023	98.28	gold quality
male germ cell	CL:0000015	98.27	gold quality
ventricular zone	UBERON:0003053	97.93	gold quality
heart right ventricle	UBERON:0002080	97.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.89	gold quality
right testis	UBERON:0004534	97.76	gold quality
left testis	UBERON:0004533	97.74	gold quality
left ventricle myocardium	UBERON:0006566	97.55	gold quality
spinal cord	UBERON:0002240	97.50	gold quality
heart left ventricle	UBERON:0002084	97.40	gold quality
cardiac ventricle	UBERON:0002082	97.38	gold quality
endothelial cell	CL:0000115	97.36	gold quality
anterior cingulate cortex	UBERON:0009835	97.35	gold quality
cingulate cortex	UBERON:0003027	97.33	gold quality
right atrium auricular region	UBERON:0006631	97.27	gold quality
primary visual cortex	UBERON:0002436	97.20	gold quality
amygdala	UBERON:0001876	97.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.19	gold quality
putamen	UBERON:0001874	97.17	gold quality
prefrontal cortex	UBERON:0000451	97.16	gold quality
right frontal lobe	UBERON:0002810	97.15	gold quality
middle temporal gyrus	UBERON:0002771	97.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.11	gold quality
cardiac atrium	UBERON:0002081	97.09	gold quality
caudate nucleus	UBERON:0001873	97.07	gold quality
substantia nigra	UBERON:0002038	97.04	gold quality
testis	UBERON:0000473	96.95	gold quality
nucleus accumbens	UBERON:0001882	96.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.87
E-MTAB-6379	no	1679.47
E-HCAD-13	no	3.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting CMC2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-924	97.78	66.21	681
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-4524B-3P	95.52	64.12	964
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-139-3P	95.24	63.10	316

Literature-anchored findings (GeneRIF, showing 1)

• Single nucleotide polymorphisms in C16orf61 gene is associated with breast cancer. (PMID:21424380)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cmc2	ENSDARG00000043635
mus_musculus	Cmc2	ENSMUSG00000014633
drosophila_melanogaster	CG42375	FBGN0259721
caenorhabditis_elegans		WBGENE00016452

Protein

Protein identifiers

COX assembly mitochondrial protein 2 homolog — Q9NRP2 (reviewed: Q9NRP2)

All UniProt accessions (8): Q9NRP2, H3BN28, H3BNN8, H3BP68, H3BPP2, H3BQQ1, H3BRC3, H3BTB6

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cytochrome c oxidase biogenesis.

Subcellular location. Mitochondrion.

Similarity. Belongs to the CMC family.

RefSeq proteins (5): NP_001338896, NP_001338897, NP_001338899, NP_001338902, NP_064573* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013892	Cyt_c_biogenesis_Cmc1-like	Family

Pfam: PF08583

UniProt features (7 total): short sequence motif 2, disulfide bond 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRP2-F1	91.60	0.86

Functional residue map

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

Disulfide bonds (2): 14–47, 24–37

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 163 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOLDRATH_ANTIGEN_RESPONSE, WEI_MYCN_TARGETS_WITH_E_BOX, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, VANTVEER_BREAST_CANCER_POOR_PROGNOSIS, FISCHER_DREAM_TARGETS, KOBAYASHI_EGFR_SIGNALING_24HR_DN, BURTON_ADIPOGENESIS_4, CUI_TCF21_TARGETS_2_UP, YNGTTNNNATT_UNKNOWN, MARSON_BOUND_BY_E2F4_UNSTIMULATED, STEIN_ESRRA_TARGETS_UP, WEST_ADRENOCORTICAL_TUMOR_UP, MORI_LARGE_PRE_BII_LYMPHOCYTE_UP

GO Biological Process (0):

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

GO Cellular Component (2): mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMC2	PROCR	Q9UNN8	928
CMC2	NSL1	Q96IY1	875
CMC2	ICAM1	P05362	823
CMC2	CMC4	P56277	731
CMC2	AWAT2	Q6E213	666
CMC2	COA4	Q9NYJ1	615
CMC2	FAM162A	Q96A26	599
CMC2	NXT2	Q9NPJ8	591
CMC2	COX19	Q49B96	564
CMC2	CHCHD7	Q9BUK0	563
CMC2	VPS29	Q9UBQ0	549
CMC2	TMEM107	Q6UX40	506
CMC2	COX11	Q9Y6N1	504
CMC2	ZNF573	Q86YE8	476
CMC2	COA6	Q5JTJ3	474

IntAct

19 interactions, top by confidence:

A	B	Type	Score
COQ5	COQ9	psi-mi:“MI:0914”(association)	0.590
C1orf216	CMC2	psi-mi:“MI:0915”(physical association)	0.560
CMC2	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
COX5B	COX7A2L	psi-mi:“MI:0914”(association)	0.530
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
FAM136A	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
ZCCHC9	S100A10	psi-mi:“MI:0914”(association)	0.350
ISX	GAPDHS	psi-mi:“MI:0914”(association)	0.350
PLGRKT	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SCO1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SFXN1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
C1orf216	CMC2	psi-mi:“MI:0915”(physical association)	0.000
CTNNA3	CMC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): CMC2 (Affinity Capture-MS), CMC2 (Affinity Capture-RNA), CMC2 (Affinity Capture-RNA), CMC2 (Affinity Capture-MS), CMC2 (Proximity Label-MS), CMC2 (Proximity Label-MS), CMC2 (Proximity Label-MS), CMC2 (Affinity Capture-MS), C1orf216 (Two-hybrid), CTNNA3 (Two-hybrid), CMC2 (Affinity Capture-MS), CMC2 (Affinity Capture-MS), CMC2 (Affinity Capture-MS), CMC2 (Affinity Capture-MS), CMC2 (Affinity Capture-MS)

ESM2 similar proteins: A1L3N6, A6ZMQ6, A9ULB4, B3LM82, B5FXK1, C8ZF59, O42921, O43715, O43920, O60200, O94581, P00429, P0CB87, P0CB88, P0CT19, P14854, P48504, P56277, P56391, Q01519, Q02379, Q0MQH3, Q0MQH4, Q0P451, Q208S3, Q28BU7, Q28CA1, Q2NKR3, Q3E7A9, Q3ZCK8, Q4R374, Q4R3M6, Q53CG4, Q5RCT0, Q5RFJ0, Q6DD38, Q6DHJ6, Q6INR6, Q6YFQ2, Q7S4H6

Diamond homologs: B5FXK1, O74347, Q28BU7, Q2NKR3, Q6DHJ6, Q8K199, Q8MNU7, Q9NRP2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3080 predictions. Top by Δscore:

Variant	Effect	Δscore
16:80981878:C:CC	acceptor_gain	1.0000
16:80997312:A:AC	donor_gain	1.0000
16:80997313:C:CC	donor_gain	1.0000
16:80997327:T:A	donor_gain	1.0000
16:81011917:T:A	acceptor_gain	1.0000
16:81011922:T:A	acceptor_gain	1.0000
16:81011925:A:AG	acceptor_gain	1.0000
16:81011926:A:AG	acceptor_gain	1.0000
16:81011926:AAAGT:A	acceptor_gain	1.0000
16:81011927:A:AG	acceptor_gain	1.0000
16:81011927:AAGT:A	acceptor_gain	1.0000
16:81011928:A:AG	acceptor_gain	1.0000
16:81011929:G:GG	acceptor_gain	1.0000
16:81011929:GT:G	acceptor_gain	1.0000
16:81011929:GTGC:G	acceptor_gain	1.0000
16:81012050:GACT:G	donor_gain	1.0000
16:81012075:G:GT	donor_gain	1.0000
16:81012082:T:TA	donor_gain	1.0000
16:81012083:A:AA	donor_gain	1.0000
16:81012109:AGGTA:A	donor_loss	1.0000
16:81012110:GGTA:G	donor_loss	1.0000
16:81012111:G:GA	donor_loss	1.0000
16:81012112:T:G	donor_loss	1.0000
16:81014179:TTT:T	donor_gain	1.0000
16:81014182:G:GG	donor_gain	1.0000
16:81014186:GT:G	donor_gain	1.0000
16:81017370:A:G	donor_gain	1.0000
16:81017748:A:AG	acceptor_gain	1.0000
16:81017748:ACTTT:A	acceptor_gain	1.0000
16:81017749:C:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017223 (16:80995754 G>A,C), RS1000021575 (16:80966837 G>A,T), RS1000069896 (16:80976983 C>T), RS1000176981 (16:81007757 A>G), RS1000212634 (16:80979214 G>A,C), RS1000264389 (16:81003806 T>A), RS1000287914 (16:80975314 T>C), RS1000309821 (16:80983248 A>C), RS1000323153 (16:80983939 C>G,T), RS1000455764 (16:81008244 T>A,C), RS1000477771 (16:80967057 T>A), RS1000495866 (16:81000513 A>G,T), RS1000567662 (16:80992614 T>C), RS1000589395 (16:80976024 G>A,C), RS1000630827 (16:80988423 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005958_20	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-06
GCST005962_30	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
sodium arsenite	increases abundance, increases expression	2
afuresertib	decreases expression	1
bisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Arsenic	increases abundance, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Daunorubicin	affects response to substance	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Selenium	decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2UJ	Abcam HEK293T CMC2 KO 1	Transformed cell line	Female
CVCL_B2UK	Abcam HEK293T CMC2 KO 2	Transformed cell line	Female

Clinical trials (associated diseases)

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