CCDC137

Summary

CCDC137 (coiled-coil domain containing 137, HGNC:33451) is a protein-coding gene on chromosome 17q25.3, encoding Coiled-coil domain-containing protein 137 (Q6PK04). It is a selective cancer dependency (DepMap: 33.4% of cell lines).

Enables RNA binding activity. Located in chromosome; nucleolus; and nucleoplasm.

Source: NCBI Gene 339230 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 69 total
• Cancer dependency (DepMap): dependent in 33.4% of screened cell lines
• MANE Select transcript: NM_199287

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33451
Approved symbol	CCDC137
Name	coiled-coil domain containing 137
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC16597
Ensembl gene	ENSG00000185298
Ensembl biotype	protein_coding
OMIM	614271
Entrez	339230

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 nonsense_mediated_decay, 2 protein_coding, 1 retained_intron

ENST00000329214, ENST00000571916, ENST00000572531, ENST00000574107, ENST00000574200, ENST00000575223

RefSeq mRNA: 1 — MANE Select: NM_199287 NM_199287

CCDS: CCDS42400

Canonical transcript exons

ENST00000329214 — 6 exons

Exon	Start	End
ENSE00001302745	81672495	81673899
ENSE00001326497	81670225	81670453
ENSE00002680165	81666737	81666900
ENSE00003513242	81667729	81667862
ENSE00003539315	81671744	81671826
ENSE00003581943	81672076	81672155

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 94.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8979 / max 161.1665, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163346	23.8979	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	94.92	gold quality
esophagus mucosa	UBERON:0002469	91.19	gold quality
mucosa of transverse colon	UBERON:0004991	90.77	gold quality
skin of leg	UBERON:0001511	90.17	gold quality
skin of abdomen	UBERON:0001416	89.97	gold quality
granulocyte	CL:0000094	89.58	gold quality
zone of skin	UBERON:0000014	88.29	gold quality
spleen	UBERON:0002106	87.91	gold quality
esophagus	UBERON:0001043	87.85	gold quality
oocyte	CL:0000023	86.49	gold quality
ectocervix	UBERON:0012249	86.42	gold quality
vermiform appendix	UBERON:0001154	86.13	gold quality
vagina	UBERON:0000996	85.96	gold quality
lymph node	UBERON:0000029	85.88	gold quality
minor salivary gland	UBERON:0001830	85.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.62	gold quality
mouth mucosa	UBERON:0003729	85.44	gold quality
body of stomach	UBERON:0001161	85.39	gold quality
right adrenal gland	UBERON:0001233	85.31	gold quality
right lobe of liver	UBERON:0001114	85.30	gold quality
metanephros cortex	UBERON:0010533	85.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.23	gold quality
right uterine tube	UBERON:0001302	85.21	gold quality
transverse colon	UBERON:0001157	85.11	gold quality
left testis	UBERON:0004533	85.08	gold quality
right adrenal gland cortex	UBERON:0035827	85.06	gold quality
left adrenal gland cortex	UBERON:0035825	85.05	gold quality
right testis	UBERON:0004534	85.04	gold quality
stromal cell of endometrium	CL:0002255	84.90	gold quality
left adrenal gland	UBERON:0001234	84.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting CCDC137, 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-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-1910-3P	98.44	67.51	1695

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• These data suggest that RaRF sequesters ERRalpha in the nucleolus through a specific interaction, thereby inhibiting its transcriptional activity. (PMID:22266318)
• HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137. (PMID:32538781)
• Prognostic Significance of CCDC137 Expression and Its Association with Immune Infiltration in Hepatocellular Carcinoma. (PMID:36061359)
• CDK12 orchestrates super-enhancer-associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer. (PMID:36254394)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc137	ENSDARG00000104024
mus_musculus	Ccdc137	ENSMUSG00000049957
rattus_norvegicus	Ccdc137	ENSRNOG00000048712
drosophila_melanogaster	CG8326	FBGN0030851

Protein

Protein identifiers

Coiled-coil domain-containing protein 137 — Q6PK04 (reviewed: Q6PK04)

All UniProt accessions (4): Q6PK04, I3L0U5, I3L385, I3L4F6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Chromosome.

RefSeq proteins (1): NP_954981* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026680	CCDC137	Family

UniProt features (16 total): region of interest 4, sequence variant 4, compositionally biased region 3, modified residue 2, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PK04-F1	74.94	0.30

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 (2): 19, 233

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, WEI_MYCN_TARGETS_WITH_E_BOX, WANG_LMO4_TARGETS_DN, MARTINEZ_RB1_TARGETS_DN, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOCC_NUCLEOLUS, BILD_MYC_ONCOGENIC_SIGNATURE, ASH1L_TARGET_GENES, CAVIN1_TARGET_GENES, CEBPZ_TARGET_GENES, ELF2_TARGET_GENES, GLI4_TARGET_GENES, HHEX_TARGET_GENES, HOXC6_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
intracellular membraneless organelle	2
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC137	TMEM69	Q5SWH9	649
CCDC137	CBLN3	Q6UW01	573
CCDC137	ZC3H10	Q96K80	562
CCDC137	CLEC19A	Q6UXS0	532
CCDC137	XKR7	Q5GH72	530
CCDC137	CCDC122	Q5T0U0	508
CCDC137	PECR	Q9BY49	507
CCDC137	NIFK	Q9BYG3	474
CCDC137	C1QTNF7	Q9BXJ2	473
CCDC137	FSAF1	Q8NDD1	444
CCDC137	PLTP	P55058	439
CCDC137	PUM3	Q15397	431
CCDC137	MMAB	Q96EY8	430
CCDC137	DDX27	Q96GQ7	419
CCDC137	CLBA1	Q96F83	414

IntAct

210 interactions, top by confidence:

A	B	Type	Score
SRP68	SRP72	psi-mi:“MI:0914”(association)	0.730
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
DHX8	AHCYL1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL8	RRP8	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
RPF1	ZNF324	psi-mi:“MI:0914”(association)	0.530

BioGRID (248): CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS)

ESM2 similar proteins: A5PJN1, O57594, O75683, P0DPK0, P53352, P70279, Q05B65, Q0VCY3, Q17QR4, Q2KIV0, Q2TBX7, Q3KRF3, Q3U155, Q3ZCI6, Q58CQ0, Q5D1Z3, Q5NVE2, Q5R939, Q5RGP9, Q5XIB5, Q5XIG5, Q5ZIH9, Q5ZMG5, Q640V3, Q641W3, Q66H19, Q6NS45, Q6PK04, Q7ZWE7, Q8BG17, Q8BK35, Q8C6C7, Q8CIL4, Q8NDD1, Q8NEF9, Q8R0K4, Q8R2N0, Q8TF30, Q96J88, Q9CR02

Diamond homologs: Q17QR4, Q6PK04, Q8R0K4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Peptide chain elongation	33	33.8×	4e-41
Viral mRNA Translation	33	33.8×	4e-41
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	33	33.4×	4e-41
Selenocysteine synthesis	33	32.0×	2e-40
Eukaryotic Translation Termination	33	32.0×	2e-40
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	33	31.3×	3e-40
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	33	31.3×	3e-40
Formation of a pool of free 40S subunits	33	29.8×	2e-39

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	34	36.2×	4e-42
maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	26.9×	6e-05
ribosomal large subunit biogenesis	10	25.5×	5e-10
maturation of SSU-rRNA	5	22.0×	2e-04
ribosomal small subunit biogenesis	16	20.9×	5e-15
translation	35	20.7×	6e-34
rRNA processing	20	16.3×	1e-16
RNA processing	9	11.3×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1168 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81667725:CCA:C	acceptor_loss	1.0000
17:81667727:A:AG	acceptor_gain	1.0000
17:81667728:G:GC	acceptor_gain	1.0000
17:81667728:GC:G	acceptor_gain	1.0000
17:81667728:GCA:G	acceptor_gain	1.0000
17:81667728:GCAA:G	acceptor_gain	1.0000
17:81667728:GCAAA:G	acceptor_gain	1.0000
17:81667730:A:AG	acceptor_gain	1.0000
17:81667852:G:GT	donor_gain	1.0000
17:81667859:GCAG:G	donor_gain	1.0000
17:81667860:CAGGT:C	donor_loss	1.0000
17:81667861:AGGTG:A	donor_loss	1.0000
17:81667862:GG:G	donor_loss	1.0000
17:81667863:G:C	donor_loss	1.0000
17:81670223:A:AG	acceptor_gain	1.0000
17:81670224:G:GT	acceptor_gain	1.0000
17:81670224:GC:G	acceptor_gain	1.0000
17:81670224:GCC:G	acceptor_gain	1.0000
17:81670224:GCCC:G	acceptor_gain	1.0000
17:81670224:GCCCA:G	acceptor_gain	1.0000
17:81670449:AAAGC:A	donor_gain	1.0000
17:81670450:AAGC:A	donor_gain	1.0000
17:81670451:AGC:A	donor_gain	1.0000
17:81670452:GC:G	donor_gain	1.0000
17:81670452:GCG:G	donor_gain	1.0000
17:81670453:CG:C	donor_loss	1.0000
17:81670454:G:GG	donor_gain	1.0000
17:81670455:T:G	donor_loss	1.0000
17:81670456:GAGTG:G	donor_loss	1.0000
17:81671742:A:AG	acceptor_gain	1.0000

AlphaMissense

1873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81672087:T:C	F198L	0.985
17:81672089:T:A	F198L	0.985
17:81672089:T:G	F198L	0.985
17:81667803:T:C	I70T	0.976
17:81667787:T:C	F65L	0.973
17:81667789:C:A	F65L	0.973
17:81667789:C:G	F65L	0.973
17:81670296:T:C	F114L	0.972
17:81670298:C:A	F114L	0.972
17:81670298:C:G	F114L	0.972
17:81670297:T:C	F114S	0.970
17:81667782:T:C	I63T	0.966
17:81670368:T:C	F138L	0.966
17:81670370:C:A	F138L	0.966
17:81670370:C:G	F138L	0.966
17:81667803:T:G	I70S	0.965
17:81667794:T:C	L67P	0.953
17:81670339:G:C	R128P	0.952
17:81667794:T:A	L67H	0.947
17:81670338:C:A	R128S	0.942
17:81670342:T:C	M129T	0.932
17:81667782:T:G	I63S	0.926
17:81670297:T:G	F114C	0.925
17:81672088:T:G	F198C	0.918
17:81667785:C:G	P64R	0.915
17:81667797:G:C	R68P	0.913
17:81672091:G:T	G199V	0.913
17:81670329:T:G	Y125D	0.912
17:81667806:T:C	M71T	0.911
17:81670353:G:C	A133P	0.911

dbSNP variants (sampled 300 via entrez): RS1000030742 (17:81667578 C>A,T), RS1000064904 (17:81672896 T>A), RS1000267608 (17:81670057 C>T), RS1000448346 (17:81673783 C>T), RS1000631619 (17:81668653 G>A), RS1000701660 (17:81669868 C>A), RS1000728610 (17:81673557 T>G), RS1000896416 (17:81669311 C>T), RS1000993262 (17:81674122 C>T), RS1001528172 (17:81670602 G>A,T), RS1001726229 (17:81670397 G>A), RS1001800344 (17:81666015 C>T), RS1002408854 (17:81674162 G>A), RS1002527638 (17:81674192 C>T), RS1002535882 (17:81671764 A>G)

Disease associations

OMIM: gene MIM:614271 | 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
GCST010002_133	Refractive error	2.000000e-50

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases expression, increases methylation, affects cotreatment	3
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	decreases expression, increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	decreases expression, increases abundance	1
Nickel	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1MF	Abcam HeLa CCDC137 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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