CMC1

Summary

CMC1 (C-X9-C motif containing 1, HGNC:28783) is a protein-coding gene on chromosome 3p24.1, encoding COX assembly mitochondrial protein homolog (Q7Z7K0). Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.

Predicted to enable metal ion binding activity. Located in mitochondrion.

Source: NCBI Gene 152100 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_182523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28783
Approved symbol	CMC1
Name	C-X9-C motif containing 1
Location	3p24.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC61571
Ensembl gene	ENSG00000187118
Ensembl biotype	protein_coding
OMIM	615166
Entrez	152100

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000334841, ENST00000396610, ENST00000418849, ENST00000423894, ENST00000466830, ENST00000467644, ENST00000468330, ENST00000469102, ENST00000477739, ENST00000482499, ENST00000495428, ENST00000897767, ENST00000897768, ENST00000897769, ENST00000897770, ENST00000897771, ENST00000922195, ENST00000922196, ENST00000922197, ENST00000971159

RefSeq mRNA: 7 — MANE Select: NM_182523 NM_001331185, NM_001331186, NM_001331187, NM_001331189, NM_001331190, NM_001412155, NM_182523

CCDS: CCDS33722, CCDS87055

Canonical transcript exons

ENST00000466830 — 4 exons

Exon	Start	End
ENSE00001525639	28241619	28241812
ENSE00001870901	28319509	28325142
ENSE00003470605	28316333	28316423
ENSE00003486079	28263291	28263380

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4066 / max 464.8089, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35780	30.8605	1818
35785	1.3702	79
35783	0.1130	33
35784	0.0629	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.09	gold quality
left ventricle myocardium	UBERON:0006566	95.39	silver quality
mucosa of transverse colon	UBERON:0004991	94.86	gold quality
spleen	UBERON:0002106	94.54	gold quality
right atrium auricular region	UBERON:0006631	93.87	gold quality
heart left ventricle	UBERON:0002084	93.86	gold quality
cardiac ventricle	UBERON:0002082	93.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.69	gold quality
heart right ventricle	UBERON:0002080	93.65	gold quality
cardiac atrium	UBERON:0002081	93.64	gold quality
myocardium	UBERON:0002349	93.21	silver quality
heart	UBERON:0000948	93.17	gold quality
vastus lateralis	UBERON:0001379	92.74	silver quality
right lobe of liver	UBERON:0001114	92.54	gold quality
epithelial cell of pancreas	CL:0000083	92.43	silver quality
adult mammalian kidney	UBERON:0000082	92.25	gold quality
quadriceps femoris	UBERON:0001377	92.02	silver quality
right adrenal gland cortex	UBERON:0035827	91.88	gold quality
right adrenal gland	UBERON:0001233	91.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.57	gold quality
transverse colon	UBERON:0001157	91.16	gold quality
left adrenal gland	UBERON:0001234	91.07	gold quality
colonic mucosa	UBERON:0000317	91.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.95	silver quality
palpebral conjunctiva	UBERON:0001812	90.90	gold quality
left adrenal gland cortex	UBERON:0035825	90.88	gold quality
leukocyte	CL:0000738	90.79	gold quality
adenohypophysis	UBERON:0002196	90.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.75	gold quality
gastrocnemius	UBERON:0001388	90.74	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	6728.74
E-HCAD-9	yes	3439.39
E-CURD-46	yes	2895.00
E-HCAD-1	yes	2695.28
E-MTAB-7407	yes	2648.06
E-HCAD-10	yes	2141.80
E-MTAB-8207	yes	1919.97
E-CURD-122	yes	1293.57
E-CURD-85	yes	1250.40
E-MTAB-8911	yes	885.62
E-HCAD-4	yes	190.40
E-MTAB-6701	yes	148.31
E-MTAB-9467	yes	66.45
E-MTAB-10287	yes	30.99
E-CURD-88	yes	29.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting CMC1, 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-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-617	96.79	65.96	738
HSA-MIR-6816-3P	95.05	66.08	459

Literature-anchored findings (GeneRIF, showing 1)

• our data indicate that CMC1 regulates turnover of newly synthesized COX1 prior to and during COX1 maturation, without affecting the rate of COX1 synthesis. (PMID:28082314)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cmc1	ENSMUSG00000039163
rattus_norvegicus	Cmc1	ENSRNOG00000010149

Protein

Protein identifiers

COX assembly mitochondrial protein homolog — Q7Z7K0 (reviewed: Q7Z7K0)

All UniProt accessions (3): C9JES7, F8WAC1, Q7Z7K0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.

Subunit / interactions. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14.

Subcellular location. Mitochondrion.

Similarity. Belongs to the CMC family.

RefSeq proteins (7): NP_001318114, NP_001318115, NP_001318116, NP_001318118, NP_001318119, NP_001399084, NP_872329* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013892	Cyt_c_biogenesis_Cmc1-like	Family

Pfam: PF08583

UniProt features (9 total): short sequence motif 2, disulfide bond 2, initiator methionine 1, chain 1, domain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7K0-F1	87.18	0.77

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

Disulfide bonds (2): 31–63, 41–53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 92 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_FOLDING, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, ACEVEDO_LIVER_CANCER_UP, NUYTTEN_EZH2_TARGETS_DN, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_ENVELOPE_LUMEN, GOCC_ORGANELLE_ENVELOPE, BRUINS_UVC_RESPONSE_LATE

GO Biological Process (0):

GO Molecular Function (1): metal ion binding (GO:0046872)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMC1	COX14	Q96I36	656
CMC1	COA3	Q9Y2R0	618
CMC1	AZI2	Q9H6S1	499
CMC1	PET117	Q6UWS5	488
CMC1	COX16	Q9P0S2	485
CMC1	ZFC3H1	O60293	480
CMC1	TMC5	Q6UXY8	455
CMC1	COA6	Q5JTJ3	443
CMC1	COA5	Q86WW8	400
CMC1	CMC2	Q9NRP2	395
CMC1	COX11	Q9Y6N1	390
CMC1	CMC4	P56277	380
CMC1	SCO1	O75880	378
CMC1	COA1	Q9GZY4	370
CMC1	CHCHD7	Q9BUK0	366
CMC1	PET100	P0DJ07	366

IntAct

13 interactions, top by confidence:

A	B	Type	Score
COA3	MT-CO1	psi-mi:“MI:0915”(physical association)	0.610
CMC1	H2BC14	psi-mi:“MI:0915”(physical association)	0.400
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CCL3L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
EDDM3A	PLXNA2	psi-mi:“MI:0914”(association)	0.350
COA3	COX5B	psi-mi:“MI:0914”(association)	0.350
COA3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMC1	MT-CO1	psi-mi:“MI:0914”(association)	0.350
SLC25A5	TMEM223	psi-mi:“MI:0914”(association)	0.350
PARL	HAX1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (14): CMC1 (Affinity Capture-RNA), HIST1H2BM (Proximity Label-MS), CMC1 (Proximity Label-MS), CMC1 (Affinity Capture-MS), CMC1 (Affinity Capture-MS), CMC1 (Affinity Capture-MS), CMC1 (Affinity Capture-MS), CMC1 (Affinity Capture-MS), CMC1 (Affinity Capture-MS), CMC1 (Proximity Label-MS), CMC1 (Affinity Capture-MS), CMC1 (Proximity Label-MS), CMC1 (Proximity Label-MS), CMC1 (Affinity Capture-MS)

ESM2 similar proteins: A8E4L1, D2K759, F1QH17, O46404, O70133, P0DI19, P35614, P35615, P62495, P62496, P62497, P62498, P83870, P83871, Q0VCX5, Q0WMV8, Q0WWE3, Q15691, Q3ZBD9, Q49B96, Q5R4C7, Q5R7Z5, Q5U2Q7, Q5XIT1, Q5ZKU1, Q5ZLC7, Q61166, Q61187, Q64143, Q66HR2, Q66T82, Q68FK8, Q6IRE4, Q6PER3, Q6V291, Q76EZ2, Q7RTV0, Q7Z7K0, Q7ZYA7, Q8BWY3

Diamond homologs: Q3SZM6, Q7Z7K0, Q9CPZ8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CMC1	“form complex”	“MITRAC complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1758 predictions. Top by Δscore:

Variant	Effect	Δscore
3:28294527:GTA:G	donor_gain	1.0000
3:28316419:GCTTA:G	donor_gain	1.0000
3:28316420:CTTA:C	donor_gain	1.0000
3:28316421:TTA:T	donor_gain	1.0000
3:28316422:TA:T	donor_gain	1.0000
3:28316423:AG:A	donor_loss	1.0000
3:28316424:G:C	donor_loss	1.0000
3:28316424:G:GG	donor_gain	1.0000
3:28316425:TAA:T	donor_loss	1.0000
3:28316426:AA:A	donor_loss	1.0000
3:28319622:GCAT:G	donor_gain	1.0000
3:28319626:G:GG	donor_gain	1.0000
3:28319653:G:GT	donor_gain	1.0000
3:28319654:A:T	donor_gain	1.0000
3:28319670:G:GT	donor_gain	1.0000
3:28319670:G:T	donor_gain	1.0000
3:28324451:CAGG:C	acceptor_gain	1.0000
3:28324455:C:CC	acceptor_gain	1.0000
3:28241808:CGCAG:C	donor_loss	0.9900
3:28241809:GCAGG:G	donor_loss	0.9900
3:28241810:CAGG:C	donor_loss	0.9900
3:28241811:AGGT:A	donor_loss	0.9900
3:28241812:GGTAC:G	donor_loss	0.9900
3:28241813:G:GA	donor_loss	0.9900
3:28241814:T:G	donor_loss	0.9900
3:28263289:A:AG	acceptor_gain	0.9900
3:28263290:G:GG	acceptor_gain	0.9900
3:28263290:GACCA:G	acceptor_gain	0.9900
3:28294525:TAGTA:T	donor_gain	0.9900
3:28294529:AGTG:A	donor_gain	0.9900

AlphaMissense

707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:28263350:G:C	A27P	0.994
3:28316380:T:A	C53S	0.994
3:28316380:T:C	C53R	0.994
3:28316381:G:C	C53S	0.994
3:28263362:T:A	C31S	0.992
3:28263363:G:C	C31S	0.992
3:28316336:T:C	F38S	0.992
3:28263351:C:A	A27D	0.991
3:28263362:T:C	C31R	0.991
3:28316335:T:C	F38L	0.991
3:28316337:T:A	F38L	0.991
3:28316337:T:G	F38L	0.991
3:28316414:T:C	L64P	0.991
3:28263327:T:A	I19N	0.990
3:28263313:A:C	E14D	0.989
3:28263313:A:T	E14D	0.989
3:28263364:T:G	C31W	0.989
3:28316336:T:G	F38C	0.989
3:28263327:T:G	I19S	0.987
3:28263363:G:A	C31Y	0.987
3:28316344:T:C	C41R	0.987
3:28263309:T:A	V13D	0.986
3:28263312:A:T	E14V	0.985
3:28263321:T:A	V17D	0.985
3:28263343:A:C	R24S	0.985
3:28263343:A:T	R24S	0.985
3:28316344:T:A	C41S	0.985
3:28316345:G:C	C41S	0.985
3:28319549:T:G	Y81D	0.984
3:28319570:T:C	F88L	0.984

dbSNP variants (sampled 300 via entrez): RS1000025137 (3:28240768 G>C), RS1000036405 (3:28241079 A>T), RS1000052229 (3:28242232 T>C,G), RS1000056636 (3:28305325 T>C), RS1000056974 (3:28260602 A>G), RS1000076939 (3:28262359 C>T), RS1000087449 (3:28304964 A>G), RS1000128842 (3:28272862 T>G), RS1000138204 (3:28283268 C>T), RS1000159358 (3:28280624 G>T), RS1000168826 (3:28264078 A>G,T), RS1000270345 (3:28245101 A>G), RS1000311757 (3:28287419 C>T), RS1000338961 (3:28313870 A>T), RS1000371374 (3:28314174 C>T)

Disease associations

OMIM: gene MIM:615166 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003622_23	Systemic lupus erythematosus	5.000000e-06
GCST004627_94	Lymphocyte count	2.000000e-14
GCST004632_140	Lymphocyte percentage of white cells	4.000000e-12
GCST005537_12	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-07
GCST005859_2	Liver transplant-free survival in primary sclerosing cholangitis (time to event)	9.000000e-07
GCST005997_9	Lymphocyte count	2.000000e-08
GCST007124_3	Multiple sclerosis and HDL levels (pleiotropy)	3.000000e-07
GCST010002_418	Refractive error	1.000000e-08
GCST011096_21	Systemic lupus erythematosus	1.000000e-08
GCST011956_74	Systemic lupus erythematosus	8.000000e-09
GCST90002388_189	Lymphocyte count	1.000000e-20
GCST90002389_13	Lymphocyte percentage of white cells	2.000000e-28
GCST90002394_230	Monocyte percentage of white cells	1.000000e-09
GCST90011866_12	Systemic lupus erythematosus	6.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
sodium arsenite	affects expression, increases abundance, increases expression	2
urushiol	increases expression	1
arsenite	increases reaction, affects binding	1
ICG 001	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Rotenone	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects expression	1

Clinical trials (associated diseases)

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