CCDC174

Summary

CCDC174 (coiled-coil domain containing 174, HGNC:28033) is a protein-coding gene on chromosome 3p25.1, encoding Coiled-coil domain-containing protein 174 (Q6PII3). Probably involved in neuronal development. It is a selective cancer dependency (DepMap: 78.1% of cell lines).

The protein encoded by this gene is found in the nucleus, where it interacts with eukaryotic translation initiation factor 4A, isoform 3. The encoded protein appears to be a part of the exon junction complex, which is involved in RNA processing, translation, and nonsense-mediated mRNA decay. A mutation in this gene has been associated with infantile hypotonia with psychomotor retardation.

Source: NCBI Gene 51244 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome (Supportive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 132 total — 1 pathogenic
• Phenotypes (HPO): 18
• Cancer dependency (DepMap): dependent in 78.1% of screened cell lines
• MANE Select transcript: NM_016474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28033
Approved symbol	CCDC174
Name	coiled-coil domain containing 174
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33839, ctr1
Ensembl gene	ENSG00000154781
Ensembl biotype	protein_coding
OMIM	616735
Entrez	51244

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000303688, ENST00000383794, ENST00000463438, ENST00000465759, ENST00000476763

RefSeq mRNA: 2 — MANE Select: NM_016474 NM_001410719, NM_016474

CCDS: CCDS2620, CCDS93219

Canonical transcript exons

ENST00000383794 — 11 exons

Exon	Start	End
ENSE00001017711	14666805	14666947
ENSE00001149830	14668049	14668181
ENSE00001149831	14667424	14667518
ENSE00003486631	14669934	14670086
ENSE00003512021	14661530	14661707
ENSE00003611328	14665028	14665123
ENSE00003656102	14658871	14658929
ENSE00003669246	14654426	14654530
ENSE00003674828	14655529	14655629
ENSE00003845953	14651762	14651878
ENSE00003847614	14670896	14672655

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 92.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.5626 / max 775.8688, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35468	25.9631	1811
35466	1.6332	845
35467	1.4224	627
35469	0.5438	267

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.85	gold quality
sural nerve	UBERON:0015488	92.58	gold quality
kidney epithelium	UBERON:0004819	91.99	silver quality
parotid gland	UBERON:0001831	90.35	gold quality
tendon	UBERON:0000043	89.82	gold quality
left ovary	UBERON:0002119	89.47	gold quality
pancreatic ductal cell	CL:0002079	89.31	silver quality
rectum	UBERON:0001052	89.15	gold quality
body of uterus	UBERON:0009853	88.36	gold quality
monocyte	CL:0000576	88.14	gold quality
right lobe of thyroid gland	UBERON:0001119	88.11	gold quality
tibial nerve	UBERON:0001323	88.08	gold quality
leukocyte	CL:0000738	88.04	gold quality
left lobe of thyroid gland	UBERON:0001120	88.01	gold quality
lower esophagus mucosa	UBERON:0035834	88.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.89	gold quality
body of stomach	UBERON:0001161	87.82	gold quality
right ovary	UBERON:0002118	87.74	gold quality
metanephros cortex	UBERON:0010533	87.72	gold quality
body of pancreas	UBERON:0001150	87.53	gold quality
thyroid gland	UBERON:0002046	87.45	gold quality
left ventricle myocardium	UBERON:0006566	87.43	gold quality
granulocyte	CL:0000094	87.42	gold quality
ileal mucosa	UBERON:0000331	87.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.28	gold quality
endocervix	UBERON:0000458	87.26	gold quality
right lobe of liver	UBERON:0001114	87.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.10	gold quality
mucosa of stomach	UBERON:0001199	87.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.01	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting CCDC174, 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-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-223-5P	99.24	68.82	1206

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• We showed that CCDC174 is ubiquitous, restricted to the cell nucleus and co-localized with EIF4A3, the CCDC174 mutation caused depletion of RYR1 and marked myopathic changes in skeletal muscle of affected individuals (PMID:26358778)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc174	ENSDARG00000023858
mus_musculus	Ccdc174	ENSMUSG00000034083
rattus_norvegicus	Ccdc174	ENSRNOG00000010090
drosophila_melanogaster	CG7183	FBGN0038583
caenorhabditis_elegans	C37A2.8	WBGENE00016494

Protein

Protein identifiers

Coiled-coil domain-containing protein 174 — Q6PII3 (reviewed: Q6PII3)

All UniProt accessions (2): Q6PII3, A0A0B4J1R8

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in neuronal development.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Disease relevance. Hypotonia, infantile, with psychomotor retardation (IHPMR) [MIM:616816] An autosomal recessive disorder characterized by congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001397648, NP_057558* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025066	CCDC174-like	Family
IPR057464	CCDC174_GRSR	Domain

Pfam: PF13300, PF25449

UniProt features (17 total): compositionally biased region 7, region of interest 4, coiled-coil region 2, chain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PII3-F1	72.79	0.26

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): 197

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): AAAYRNCTG_UNKNOWN, YY1_Q6, AFP1_Q6, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, FREAC7_01, CETS1P54_01, GCCATNTTG_YY1_Q6, SCGGAAGY_ELK1_02, POS_RESPONSE_TO_HISTAMINE_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, ELK1_02, MARTENS_BOUND_BY_PML_RARA_FUSION, EIF4E_DN, ARID5B_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1087 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC174	TATDN2	Q93075	595
CCDC174	NOM1	Q5C9Z4	514
CCDC174	ALPK3	Q96L96	505
CCDC174	GPR22	Q99680	487
CCDC174	NRDE2	Q9H7Z3	481
CCDC174	TMCO2	Q7Z6W1	479
CCDC174	MRPL50	Q8N5N7	389
CCDC174	DNM1L	O00429	385
CCDC174	PRPF18	Q99633	376
CCDC174	ZNF814	B7Z6K7	372
CCDC174	GPBP1	Q86WP2	371
CCDC174	IQCE	Q6IPM2	370
CCDC174	GGNBP2	Q9H3C7	366
CCDC174	CRBN	Q96SW2	356
CCDC174	ANKRD11	Q6UB99	354

IntAct

34 interactions, top by confidence:

A	B	Type	Score
EIF4A3	CASC3	psi-mi:“MI:0914”(association)	0.980
EIF4A3	CCDC174	psi-mi:“MI:0915”(physical association)	0.740
FLII	TMOD1	psi-mi:“MI:0914”(association)	0.640
ALOX5	CCDC174	psi-mi:“MI:0915”(physical association)	0.560
NAA10	CCDC174	psi-mi:“MI:0915”(physical association)	0.560
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
GSK3A	CCDC174	psi-mi:“MI:0915”(physical association)	0.370
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
SMC6	IFT88	psi-mi:“MI:0914”(association)	0.350
ZWINT	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Bach1	SYNM	psi-mi:“MI:0914”(association)	0.350
Eloc	SF3B2	psi-mi:“MI:0914”(association)	0.350
Setdb1	INPP5B	psi-mi:“MI:0914”(association)	0.350
RNF168	PSMD11	psi-mi:“MI:0914”(association)	0.350
CERK	WDR46	psi-mi:“MI:0914”(association)	0.350
KLC3	KLC1	psi-mi:“MI:0914”(association)	0.350
MYH13	C1orf226	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
FLII	STRN	psi-mi:“MI:0914”(association)	0.350
CCDC174	AMY1A	psi-mi:“MI:0914”(association)	0.350
IFNA21	OASL	psi-mi:“MI:0914”(association)	0.350
KLF16	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
EIF4A3	CCDC174	psi-mi:“MI:0915”(physical association)	0.000
ALOX5	CCDC174	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): CCDC174 (Two-hybrid), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-MS), CCDC174 (Affinity Capture-RNA), CCDC174 (Proximity Label-MS), CCDC174 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WRI3, A2BFC9, A2RRW4, A4QMS7, A6NJV1, A6NL82, A6QPC0, A6QQ68, A8E4X8, A8E5W8, A8QW39, A9JS51, D6REC4, F1P3Y5, G3X6E2, P0C875, Q0VB26, Q1MSJ5, Q2IA00, Q2T9Q3, Q2TA11, Q3UY96, Q494V2, Q497Q6, Q4KKZ1, Q4QR77, Q4R5Y0, Q4R8V8, Q5NC57, Q5ZIH9, Q6J272, Q6PII3, Q6ZQR2, Q6ZVS7, Q7Z4T9, Q8CFW7, Q8N1D5, Q8N6G2, Q8WW14, Q95LR0

Diamond homologs: Q3U155, Q5PQS7, Q5ZIH9, Q6PII3, Q8GWI5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	80
Likely benign	22
Benign	18

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
222080	NM_016474.5(CCDC174):c.1404A>G (p.Ter468Trp)	Pathogenic

SpliceAI

1403 predictions. Top by Δscore:

Variant	Effect	Δscore
3:14654419:A:AG	acceptor_gain	1.0000
3:14654420:T:G	acceptor_gain	1.0000
3:14654424:A:AG	acceptor_gain	1.0000
3:14654424:AGTT:A	acceptor_gain	1.0000
3:14654424:AGTTG:A	acceptor_gain	1.0000
3:14654425:G:GC	acceptor_gain	1.0000
3:14654425:GT:G	acceptor_gain	1.0000
3:14654425:GTT:G	acceptor_gain	1.0000
3:14654425:GTTG:G	acceptor_gain	1.0000
3:14654425:GTTGG:G	acceptor_gain	1.0000
3:14654528:AAGGT:A	donor_loss	1.0000
3:14654532:T:G	donor_loss	1.0000
3:14655514:A:AG	acceptor_gain	1.0000
3:14655515:A:AG	acceptor_gain	1.0000
3:14655516:A:AG	acceptor_gain	1.0000
3:14655517:A:G	acceptor_gain	1.0000
3:14655518:T:G	acceptor_gain	1.0000
3:14655520:A:AG	acceptor_gain	1.0000
3:14655521:T:G	acceptor_gain	1.0000
3:14655527:A:AG	acceptor_gain	1.0000
3:14655527:A:T	acceptor_loss	1.0000
3:14655528:G:GG	acceptor_gain	1.0000
3:14655528:GA:G	acceptor_gain	1.0000
3:14655528:GAA:G	acceptor_gain	1.0000
3:14655528:GAAA:G	acceptor_gain	1.0000
3:14655625:GCAAG:G	donor_gain	1.0000
3:14655629:GGT:G	donor_loss	1.0000
3:14655629:GGTA:G	donor_gain	1.0000
3:14655630:GTA:G	donor_gain	1.0000
3:14655631:T:A	donor_gain	1.0000

AlphaMissense

3096 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:14654436:T:C	L18P	0.999
3:14654448:T:C	L22P	0.999
3:14654436:T:A	L18H	0.998
3:14654441:G:C	A20P	0.998
3:14654454:G:C	R24P	0.998
3:14658890:G:C	A90P	0.998
3:14661562:T:C	F114L	0.998
3:14661564:C:A	F114L	0.998
3:14661564:C:G	F114L	0.998
3:14665053:C:A	R171S	0.998
3:14665054:G:C	R171P	0.998
3:14665060:G:C	R173P	0.998
3:14667508:T:C	L270P	0.998
3:14667511:G:C	R271P	0.998
3:14670071:T:A	W364R	0.998
3:14670071:T:C	W364R	0.998
3:14661706:T:A	W162R	0.997
3:14661706:T:C	W162R	0.997
3:14665041:G:C	D167H	0.997
3:14666867:G:C	R215P	0.997
3:14667457:T:C	F253S	0.997
3:14670073:G:C	W364C	0.997
3:14670073:G:T	W364C	0.997
3:14658889:A:C	K89N	0.996
3:14658889:A:T	K89N	0.996
3:14661563:T:C	F114S	0.996
3:14665043:C:A	D167E	0.996
3:14665043:C:G	D167E	0.996
3:14666877:G:C	W218C	0.996
3:14666877:G:T	W218C	0.996

dbSNP variants (sampled 300 via entrez): RS1000129873 (3:14652396 G>C), RS1000172495 (3:14658503 G>A), RS1000188976 (3:14652069 T>C), RS1000595741 (3:14664031 T>G), RS1000767526 (3:14670627 A>G,T), RS1000990539 (3:14670743 T>C), RS1001158688 (3:14666250 T>C), RS1001234817 (3:14667827 C>T), RS1001260678 (3:14661339 A>G), RS1001666385 (3:14653462 AG>A), RS1001786861 (3:14672605 G>A), RS1001837485 (3:14656953 A>G), RS1002000717 (3:14651241 G>A,C), RS1002036756 (3:14656652 A>T), RS1002134312 (3:14655227 C>G)

Disease associations

OMIM: gene MIM:616735 | disease phenotypes: MIM:616816

GenCC curated gene-disease

Disease	Classification	Inheritance
severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome	Supportive	Autosomal recessive

Mondo (1): severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome (MONDO:0014784)

Orphanet (1): Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome (Orphanet:467176)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000194	Open mouth
HP:0000276	Long face
HP:0000486	Strabismus
HP:0000750	Delayed speech and language development
HP:0001263	Global developmental delay
HP:0001319	Neonatal hypotonia
HP:0001558	Decreased fetal movement
HP:0001629	Ventricular septal defect
HP:0002058	Myopathic facies
HP:0002079	Hypoplasia of the corpus callosum
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0003198	Myopathy
HP:0003557	Increased variability in muscle fiber diameter
HP:0006829	Severe muscular hypotonia
HP:0006897	Abducens palsy
HP:0006956	Lateral ventricle dilatation

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012796_2	Sjögren’s syndrome	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	increases expression, increases abundance	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Phthalic Acids	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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