CCDC59

Summary

CCDC59 (coiled-coil domain containing 59, HGNC:25005) is a protein-coding gene on chromosome 12q21.31, encoding Thyroid transcription factor 1-associated protein 26 (Q9P031). Component of the transcription complexes of the pulmonary surfactant-associated protein-B (SFTPB) and -C (SFTPC). It is a selective cancer dependency (DepMap: 84.4% of cell lines).

Enables RNA binding activity. Predicted to be located in nucleoplasm.

Source: NCBI Gene 29080 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total
• Cancer dependency (DepMap): dependent in 84.4% of screened cell lines
• MANE Select transcript: NM_014167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25005
Approved symbol	CCDC59
Name	coiled-coil domain containing 59
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Aliases	HSPC128, TAP26, BR22
Ensembl gene	ENSG00000133773
Ensembl biotype	protein_coding
OMIM	619280
Entrez	29080

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000256151, ENST00000547758, ENST00000548126, ENST00000550589, ENST00000552377, ENST00000552412, ENST00000552606, ENST00000930495, ENST00000930496

RefSeq mRNA: 1 — MANE Select: NM_014167 NM_014167

CCDS: CCDS9023

Canonical transcript exons

ENST00000256151 — 4 exons

Exon	Start	End
ENSE00000910617	82352303	82353312
ENSE00002408581	82358223	82358387
ENSE00003538009	82356960	82357269
ENSE00003634904	82354495	82354594

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.3157 / max 930.7114, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132323	42.8532	1811
132324	10.0221	1733
132325	1.4404	842

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.56	gold quality
oocyte	CL:0000023	99.50	gold quality
tendon of biceps brachii	UBERON:0008188	98.11	gold quality
tendon	UBERON:0000043	97.25	gold quality
calcaneal tendon	UBERON:0003701	97.16	gold quality
monocyte	CL:0000576	96.67	gold quality
mononuclear cell	CL:0000842	96.62	gold quality
leukocyte	CL:0000738	96.12	gold quality
cartilage tissue	UBERON:0002418	93.81	gold quality
left ovary	UBERON:0002119	93.66	gold quality
medial globus pallidus	UBERON:0002477	93.50	gold quality
peritoneum	UBERON:0002358	93.25	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.25	gold quality
omental fat pad	UBERON:0010414	93.25	gold quality
left testis	UBERON:0004533	92.92	gold quality
ovary	UBERON:0000992	92.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.89	gold quality
testis	UBERON:0000473	92.75	gold quality
bone marrow	UBERON:0002371	92.71	gold quality
bone marrow cell	CL:0002092	92.57	gold quality
right lung	UBERON:0002167	92.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.47	gold quality
right testis	UBERON:0004534	92.37	gold quality
lymph node	UBERON:0000029	92.36	gold quality
rectum	UBERON:0001052	92.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.21	gold quality
adipose tissue	UBERON:0001013	92.17	gold quality
hair follicle	UBERON:0002073	92.17	gold quality
connective tissue	UBERON:0002384	92.17	gold quality
mucosa of stomach	UBERON:0001199	92.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TTF1

miRNA regulators (miRDB)

53 targeting CCDC59, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-12122	99.56	69.33	1672

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.4% of screened cell lines.

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc59	ENSDARG00000045755
mus_musculus	Ccdc59	ENSMUSG00000019897
rattus_norvegicus	Ccdc59	ENSRNOG00000004183
caenorhabditis_elegans		WBGENE00017360

Protein

Protein identifiers

Thyroid transcription factor 1-associated protein 26 — Q9P031 (reviewed: Q9P031)

Alternative names: Coiled-coil domain-containing protein 59, TTF-1-associated protein BR2

All UniProt accessions (2): Q9P031, F8VNY5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the transcription complexes of the pulmonary surfactant-associated protein-B (SFTPB) and -C (SFTPC). Enhances homeobox protein Nkx-2.1-activated SFTPB and SFTPC promoter activities.

Subunit / interactions. Interacts with NKX2-1.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed. In lung, expression is restricted to the alveolar epithelial cells.

Similarity. Belongs to the TAP26 family.

RefSeq proteins (1): NP_054886* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013730	Fyv7/TAP26	Family

Pfam: PF08524

UniProt features (6 total): region of interest 2, sequence conflict 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P031-F1	74.09	0.38

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5683826	Surfactant metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 143 (showing top): WANG_CLIM2_TARGETS_UP, WEI_MYCN_TARGETS_WITH_E_BOX, BLALOCK_ALZHEIMERS_DISEASE_UP, chr12q21, GNF2_FBL, DODD_NASOPHARYNGEAL_CARCINOMA_UP, HAMAI_APOPTOSIS_VIA_TRAIL_UP, ERBB2_UP.V1_DN, CSR_EARLY_UP.V1_UP, REACTOME_SURFACTANT_METABOLISM, ESC_J1_UP_EARLY.V1_DN, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_UP, CEBPZ_TARGET_GENES, CHAF1B_TARGET_GENES, CIITA_TARGET_GENES

GO Biological Process (0):

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

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC59	ZNF75D	P51815	459
CCDC59	CXCL11	O14625	446
CCDC59	MRPL55	Q7Z7F7	438
CCDC59	RBM42	Q9BTD8	430
CCDC59	ZNF630	Q2M218	418
CCDC59	ZNF296	Q8WUU4	406
CCDC59	URAD	A6NGE7	379
CCDC59	ZNF615	Q8N8J6	358
CCDC59	CCDC85B	Q15834	346
CCDC59	ZNF404	Q494X3	327
CCDC59	ARHGEF26	Q96DR7	327
CCDC59	TNFRSF13C	Q96RJ3	323
CCDC59	ADCY9	O60503	318
CCDC59	NOL10	Q9BSC4	300
CCDC59	ZNF33A	P17013	296
CCDC59	ZNF415	Q09FC8	296

IntAct

76 interactions, top by confidence:

A	B	Type	Score
NKX2-1	CCDC59	psi-mi:“MI:0915”(physical association)	0.580
CCDC59	NKX2-1	psi-mi:“MI:0915”(physical association)	0.580
MAGEA8	CCDC59	psi-mi:“MI:0915”(physical association)	0.560
CCDC59	GAPDHS	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
CCDC59		psi-mi:“MI:0915”(physical association)	0.370
FOXL2	RTCA	psi-mi:“MI:0914”(association)	0.350
k8	RGL2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CCDC59	IPO5	psi-mi:“MI:0914”(association)	0.350
RPS14	RRP8	psi-mi:“MI:0914”(association)	0.350
KLF8		psi-mi:“MI:0914”(association)	0.350
IPO5	C11orf98	psi-mi:“MI:0914”(association)	0.350
NPM1	RPS3A	psi-mi:“MI:0914”(association)	0.350
NPM3	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPL15	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
	LAMA5	psi-mi:“MI:0914”(association)	0.350
	PES1	psi-mi:“MI:0914”(association)	0.350
	POLR3A	psi-mi:“MI:0914”(association)	0.350
	RTCA	psi-mi:“MI:0914”(association)	0.350
SERF2	WDR46	psi-mi:“MI:0914”(association)	0.350
IFI27L1	KIF1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (144): CCDC59 (Affinity Capture-MS), CCDC59 (Reconstituted Complex), CCDC59 (Proximity Label-MS), CCDC59 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), HAUS4 (Affinity Capture-MS), HAUS1 (Affinity Capture-MS), CENPB (Affinity Capture-MS), URB1 (Affinity Capture-MS), EDC3 (Affinity Capture-MS), LRP2 (Affinity Capture-MS), COG4 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS), LENG8 (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: A5PJN1, Q5RGP9, Q8R2N0, Q9P031

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Eukaryotic Translation Initiation	5	27.6×	1e-05
Cap-dependent Translation Initiation	5	27.6×	1e-05
SARS-CoV-1 modulates host translation machinery	5	27.6×	1e-05
Peptide chain elongation	11	24.9×	5e-11
Viral mRNA Translation	11	24.9×	5e-11
Eukaryotic Translation Elongation	5	24.9×	2e-05
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	11	24.6×	5e-11
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	24.3×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	12	29.6×	3e-12
ribosomal small subunit biogenesis	8	24.3×	2e-07
translation	11	15.1×	4e-08
rRNA processing	6	11.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

668 predictions. Top by Δscore:

Variant	Effect	Δscore
12:82354488:AACTT:A	donor_loss	1.0000
12:82354489:ACTT:A	donor_loss	1.0000
12:82354490:CTTAC:C	donor_loss	1.0000
12:82354491:TTAC:T	donor_loss	1.0000
12:82354493:A:AC	donor_gain	1.0000
12:82354494:C:A	donor_loss	1.0000
12:82354494:C:CC	donor_gain	1.0000
12:82354494:CT:C	donor_gain	1.0000
12:82354494:CTT:C	donor_gain	1.0000
12:82354494:CTTG:C	donor_gain	1.0000
12:82354494:CTTGT:C	donor_gain	1.0000
12:82354595:C:CC	acceptor_gain	1.0000
12:82354596:T:C	acceptor_gain	1.0000
12:82354598:T:C	acceptor_gain	1.0000
12:82354598:T:TC	acceptor_gain	1.0000
12:82354602:T:C	acceptor_gain	1.0000
12:82354602:T:TC	acceptor_gain	1.0000
12:82356955:CATA:C	donor_gain	1.0000
12:82356956:ATACT:A	donor_loss	1.0000
12:82356957:TA:T	donor_loss	1.0000
12:82356958:A:AC	donor_gain	1.0000
12:82356958:ACT:A	donor_loss	1.0000
12:82356959:C:CT	donor_gain	1.0000
12:82356959:CTT:C	donor_gain	1.0000
12:82356959:CTTT:C	donor_gain	1.0000
12:82356959:CTTTA:C	donor_gain	1.0000
12:82356963:A:AC	donor_gain	1.0000
12:82356964:C:CC	donor_gain	1.0000
12:82358754:G:GT	donor_gain	1.0000
12:82353310:TTCC:T	acceptor_loss	0.9900

AlphaMissense

1599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:82357259:A:C	F55L	0.987
12:82357259:A:T	F55L	0.987
12:82357261:A:G	F55L	0.987
12:82353179:A:G	L233P	0.983
12:82353279:C:G	A200P	0.979
12:82353176:A:G	L234P	0.975
12:82353221:G:A	T219I	0.972
12:82353200:A:G	L226S	0.970
12:82354511:C:G	R183P	0.967
12:82353167:A:G	I237T	0.966
12:82353253:T:A	K208N	0.965
12:82353253:T:G	K208N	0.965
12:82357264:C:G	G54R	0.964
12:82353241:A:C	F212L	0.963
12:82353241:A:T	F212L	0.963
12:82353243:A:G	F212L	0.963
12:82353212:C:T	G222D	0.962
12:82353207:G:A	P224S	0.960
12:82353233:A:G	L215P	0.960
12:82358223:C:G	G52R	0.960
12:82358223:C:T	G52R	0.960
12:82353213:C:G	G222R	0.955
12:82357257:G:T	A56D	0.954
12:82353208:T:A	Q223H	0.953
12:82353208:T:G	Q223H	0.953
12:82357260:A:G	F55S	0.950
12:82357247:T:A	R59S	0.949
12:82357247:T:G	R59S	0.949
12:82354545:C:G	A172P	0.945
12:82353212:C:A	G222V	0.943

dbSNP variants (sampled 300 via entrez): RS1000030681 (12:82352199 A>G), RS1000094447 (12:82352790 G>C), RS1000132815 (12:82355622 C>T), RS1000484862 (12:82355484 A>G,T), RS1000695433 (12:82360717 G>T), RS1000780656 (12:82356603 T>C), RS1000811419 (12:82356904 G>A), RS1001132222 (12:82360457 T>C), RS1001516869 (12:82360015 A>T), RS1001599868 (12:82355053 G>A,C,T), RS1001628412 (12:82356237 T>G), RS1003159371 (12:82358961 G>A,C,T), RS1003666006 (12:82353791 A>C,G), RS1003757925 (12:82352625 T>C), RS1004625094 (12:82353374 G>A,T)

Disease associations

OMIM: gene MIM:619280 | 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
GCST002563_22	Hypospadias	6.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
(+)-JQ1 compound	decreases expression	2
Arsenic	increases expression, affects expression, affects cotreatment, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Disulfiram	affects binding, decreases expression	1

Clinical trials (associated diseases)

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