CCDC12

Summary

CCDC12 (coiled-coil domain containing 12, HGNC:28332) is a protein-coding gene on chromosome 3p21.31, encoding Coiled-coil domain-containing protein 12 (Q8WUD4). It is a selective cancer dependency (DepMap: 14.7% of cell lines).

Predicted to be located in nucleoplasm. Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex.

Source: NCBI Gene 151903 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 61 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 14.7% of screened cell lines
• MANE Select transcript: NM_001277074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28332
Approved symbol	CCDC12
Name	coiled-coil domain containing 12
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC23918
Ensembl gene	ENSG00000160799
Ensembl biotype	protein_coding
Entrez	151903

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 8 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000292314, ENST00000425441, ENST00000446836, ENST00000460035, ENST00000488069, ENST00000492819, ENST00000494655, ENST00000603885, ENST00000604164, ENST00000604181, ENST00000604367, ENST00000605358, ENST00000605875, ENST00000683445, ENST00000718454, ENST00000878135, ENST00000878136, ENST00000878137, ENST00000928986

RefSeq mRNA: 2 — MANE Select: NM_001277074 NM_001277074, NM_144716

CCDS: CCDS2748, CCDS63612

Canonical transcript exons

ENST00000683445 — 7 exons

Exon	Start	End
ENSE00001054558	46922236	46922312
ENSE00003459891	46940998	46941065
ENSE00003464706	46923329	46923363
ENSE00003509118	46923607	46923668
ENSE00003788319	46925456	46925535
ENSE00003918750	46921730	46922139
ENSE00003920152	46976637	46976745

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7231 / max 242.9265, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42018	19.2875	1810
42019	0.4356	238

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.24	gold quality
monocyte	CL:0000576	96.57	gold quality
leukocyte	CL:0000738	96.27	gold quality
lower esophagus mucosa	UBERON:0035834	96.19	gold quality
skin of abdomen	UBERON:0001416	95.78	gold quality
skin of leg	UBERON:0001511	95.74	gold quality
pancreatic ductal cell	CL:0002079	95.69	gold quality
esophagus mucosa	UBERON:0002469	95.67	gold quality
tendon of biceps brachii	UBERON:0008188	95.17	gold quality
kidney epithelium	UBERON:0004819	94.98	gold quality
zone of skin	UBERON:0000014	94.87	gold quality
granulocyte	CL:0000094	94.79	gold quality
islet of Langerhans	UBERON:0000006	94.78	gold quality
left adrenal gland	UBERON:0001234	94.78	gold quality
left adrenal gland cortex	UBERON:0035825	94.76	gold quality
apex of heart	UBERON:0002098	94.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.71	gold quality
mucosa of transverse colon	UBERON:0004991	94.67	gold quality
calcaneal tendon	UBERON:0003701	94.65	gold quality
adrenal cortex	UBERON:0001235	94.53	gold quality
upper arm skin	UBERON:0004263	94.51	gold quality
ileal mucosa	UBERON:0000331	94.41	gold quality
tendon	UBERON:0000043	94.28	gold quality
right adrenal gland	UBERON:0001233	94.26	gold quality
ectocervix	UBERON:0012249	94.11	gold quality
adrenal gland	UBERON:0002369	94.05	gold quality
esophagus	UBERON:0001043	94.01	gold quality
right lobe of thyroid gland	UBERON:0001119	94.01	gold quality
nasal cavity epithelium	UBERON:0005384	93.93	gold quality
lymph node	UBERON:0000029	93.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	205.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting CCDC12, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-4649-5P	93.02	63.85	141
HSA-MIR-6729-5P	93.02	62.76	138

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• CCDC12 is a new participant that promotes early erythroid differentiation. (PMID:22269669)
• It was suggested that rs1076394 served as an expression Quantitative Trait Loci (eQTL) for gene CCDC12 and NME6, while NME6’s expression was obviously higher in colorectal cancer tissues. (PMID:27120998)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc12	ENSDARG00000023003
mus_musculus	Ccdc12	ENSMUSG00000019659
rattus_norvegicus	Ccdc12	ENSRNOG00000020946
drosophila_melanogaster	CG15525	FBGN0039732
caenorhabditis_elegans		WBGENE00022092

Protein

Protein identifiers

Coiled-coil domain-containing protein 12 — Q8WUD4 (reviewed: Q8WUD4)

All UniProt accessions (4): Q8WUD4, C9JUN5, J3KR35, S4R331

RefSeq proteins (2): NP_001264003, NP_653317 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013169	mRNA_splic_Cwf18-like	Family

Pfam: PF08315

UniProt features (12 total): modified residue 4, region of interest 2, coiled-coil region 2, chain 1, cross-link 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9FMD	ELECTRON MICROSCOPY	3.3
8RO2	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUD4-F1	76.01	0.28

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 (5): 94, 1, 53, 149, 165

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 98 (showing top): REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, REACTOME_MRNA_SPLICING, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, DODD_NASOPHARYNGEAL_CARCINOMA_DN, KEGG_SPLICEOSOME, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_17, GOCC_POST_MRNA_RELEASE_SPLICEOSOMAL_COMPLEX, chr3p21, NRF1_Q6, ARID5B_TARGET_GENES, CEBPZ_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (3): nucleoplasm (GO:0005654), U2-type spliceosomal complex (GO:0005684), post-mRNA release spliceosomal complex (GO:0071014)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
spliceosomal complex	2
binding	1
nuclear lumen	1
cellular anatomical structure	1
U5 snRNP	1

Protein interactions and networks

STRING

966 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC12	FAM76A	Q8TAV0	685
CCDC12	KIF9	Q9HAQ2	544
CCDC12	NBEAL2	Q6ZNJ1	524
CCDC12	KLHL18	O94889	513
CCDC12	CCDC18	Q5T9S5	476
CCDC12	WDR83	Q9BRX9	471
CCDC12	POLR1F	Q3B726	458
CCDC12	NGLY1	Q96IV0	458
CCDC12	LSM8	O95777	457
CCDC12	CCDC13	Q8IYE1	448
CCDC12	CEP126	Q9P2H0	434
CCDC12	PPIH	O43447	433
CCDC12	POLR2E	P19388	425
CCDC12	CEP131	Q9UPN4	398
CCDC12	CXorf65	A6NEN9	398

IntAct

116 interactions, top by confidence:

A	B	Type	Score
ATG5	ATG12	psi-mi:“MI:0914”(association)	0.800
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
CCDC12	ATG5	psi-mi:“MI:0915”(physical association)	0.740
SYF2	AQR	psi-mi:“MI:0914”(association)	0.730
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
DHX8	AHCYL1	psi-mi:“MI:0914”(association)	0.640
LRRC46	TFPT	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
CRNKL1	CCDC12	psi-mi:“MI:0915”(physical association)	0.630
CCDC12	CRNKL1	psi-mi:“MI:0915”(physical association)	0.630
EFTUD2	SART1	psi-mi:“MI:0914”(association)	0.610
DVL3	DVL2	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
PRPF19	STRN	psi-mi:“MI:0914”(association)	0.530
KIAA1143	AQR	psi-mi:“MI:0914”(association)	0.530
RALYL	CDC40	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530

BioGRID (162): CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS)

ESM2 similar proteins: A7SD85, B0W6N3, O08837, O57476, O88346, P02641, P02642, P02646, P06398, P08057, P09741, P12620, P13789, P13805, P19351, P19429, P23693, P27672, P27673, P45378, P45379, P48787, P50751, P50752, P50753, P50754, P68246, P68247, P92948, Q16543, Q173M7, Q27371, Q2KJC1, Q39604, Q5EAC6, Q5PYI0, Q61081, Q63692, Q6A068, Q75NG9

Diamond homologs: P0CV38, Q8R344, Q8WUD4, Q9UU80

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
Metabolism of non-coding RNA	5	36.9×	5e-06
mRNA Splicing	26	33.2×	2e-31
mRNA Splicing - Major Pathway	43	27.3×	2e-50
Processing of Capped Intron-Containing Pre-mRNA	28	26.8×	3e-31
RNA Polymerase II Transcription Termination	9	23.0×	7e-09
mRNA Polyadenylation	22	22.5×	1e-22
mRNA Splicing - Minor Pathway	8	20.8×	1e-07
mRNA 3’-end processing	8	18.3×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	10	57.8×	1e-13
spliceosomal snRNP assembly	9	48.4×	2e-11
RNA splicing, via transesterification reactions	7	40.5×	3e-08
spliceosomal complex assembly	6	33.4×	2e-06
mRNA splicing, via spliceosome	39	33.1×	5e-47
RNA splicing	23	18.8×	9e-21
RNA processing	6	12.2×	5e-04
mRNA processing	11	8.0×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
154800	GRCh38/hg38 3p21.31(chr3:46726614-46968315)x1	Pathogenic

SpliceAI

1313 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46922234:A:AC	donor_gain	1.0000
3:46922235:C:CA	donor_gain	1.0000
3:46922235:CGG:C	donor_gain	1.0000
3:46922235:CGGA:C	donor_gain	1.0000
3:46922235:CGGAT:C	donor_gain	1.0000
3:46922308:GGTCC:G	acceptor_gain	1.0000
3:46922309:GTCC:G	acceptor_gain	1.0000
3:46922310:TCC:T	acceptor_gain	1.0000
3:46922311:CC:C	acceptor_gain	1.0000
3:46922311:CCC:C	acceptor_gain	1.0000
3:46922312:CC:C	acceptor_gain	1.0000
3:46922313:C:CC	acceptor_gain	1.0000
3:46922319:C:CT	acceptor_gain	1.0000
3:46922320:A:T	acceptor_gain	1.0000
3:46923324:CTCA:C	donor_loss	1.0000
3:46923326:CA:C	donor_loss	1.0000
3:46923327:A:AC	donor_gain	1.0000
3:46923328:C:CC	donor_gain	1.0000
3:46923362:TC:T	acceptor_gain	1.0000
3:46923363:CC:C	acceptor_gain	1.0000
3:46923364:C:CC	acceptor_gain	1.0000
3:46923364:C:CG	acceptor_loss	1.0000
3:46923365:T:A	acceptor_loss	1.0000
3:46923603:TCACC:T	donor_loss	1.0000
3:46923606:CCA:C	donor_gain	1.0000
3:46923611:T:TA	donor_gain	1.0000
3:46923667:CA:C	acceptor_gain	1.0000
3:46923667:CACT:C	acceptor_loss	1.0000
3:46923668:ACT:A	acceptor_loss	1.0000
3:46923669:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046086 (3:46962451 A>G), RS1000052304 (3:46926324 G>A), RS1000104913 (3:46956142 C>T), RS1000112733 (3:46927644 A>T), RS1000231189 (3:46970427 G>A), RS1000242537 (3:46983512 G>A), RS1000266128 (3:46938641 A>C,G), RS1000320741 (3:46932107 C>A,G), RS1000347731 (3:46976434 G>A,T), RS1000474094 (3:46957677 C>T), RS1000500687 (3:46964354 A>G), RS1000597339 (3:46950751 G>A), RS1000606892 (3:46924508 G>A), RS1000637676 (3:46938358 G>A), RS1000675521 (3:46926077 C>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:139090

GenCC curated gene-disease

Mondo (1): gray platelet syndrome (MONDO:0007686)

Orphanet (1): Gray platelet syndrome (Orphanet:721)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004691_3	Huntington’s disease progression	2.000000e-06
GCST005973_25	White blood cell count	1.000000e-09
GCST007576_323	Chronotype	3.000000e-11
GCST008839_41	Height	2.000000e-21
GCST009597_206	Multiple sclerosis	4.000000e-07
GCST010002_422	Refractive error	4.000000e-14
GCST90002383_365	Hematocrit	1.000000e-10
GCST90002384_205	Hemoglobin	8.000000e-10
GCST90016667_3	Spleen volume	2.000000e-08
GCST90020024_1141	A body shape index	3.000000e-10
GCST90020025_1942	Waist-to-hip ratio adjusted for BMI	2.000000e-16
GCST90020025_1943	Waist-to-hip ratio adjusted for BMI	1.000000e-13
GCST90020026_193	Hip index	2.000000e-11
GCST90020027_173	Waist-hip index	7.000000e-17
GCST90020027_174	Waist-hip index	1.000000e-13

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0008328	chronotype measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D055652	Gray Platelet Syndrome	C15.378.140.427; C16.320.099.417

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4682844	CCDC12		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, decreases reaction, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
ginger extract	increases abundance, decreases expression, decreases reaction	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
trichostatin A	affects expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
Resveratrol	affects cotreatment, increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Cisplatin	decreases expression	1
Dietary Carbohydrates	decreases expression	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Oils, Volatile	increases abundance, decreases expression, decreases reaction	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Vincristine	decreases expression	1
Copper Sulfate	increases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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