CCDC28A

Summary

CCDC28A (coiled-coil domain containing 28A, HGNC:21098) is a protein-coding gene on chromosome 6q24.1, encoding Coiled-coil domain-containing protein 28A (Q8IWP9).

This gene encodes a coiled-coil domain containing protein. Although the specific function of this gene has not yet been determined, this gene is a known translocation partner of nucleoporin 98 in acute leukemias. The resulting fusion gene produces a nucleoporin 98-coiled-coil domain-containing protein 28A chimeric protein which may be involved in promoting myeloproliferative neoplasms.

Source: NCBI Gene 25901 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_015439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21098
Approved symbol	CCDC28A
Name	coiled-coil domain containing 28A
Location	6q24.1
Locus type	gene with protein product
Status	Approved
Aliases	CCRL1AP, DKFZp586D0623, LTAP2A
Ensembl gene	ENSG00000024862
Ensembl biotype	protein_coding
OMIM	615353
Entrez	25901

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000617445, ENST00000864346, ENST00000864347, ENST00000864348

RefSeq mRNA: 1 — MANE Select: NM_015439 NM_015439

CCDS: CCDS5192

Canonical transcript exons

ENST00000617445 — 6 exons

Exon	Start	End
ENSE00000764737	138779822	138779985
ENSE00001002798	138788366	138788388
ENSE00001265534	138785227	138785381
ENSE00001946346	138792749	138793319
ENSE00003731348	138776079	138776278
ENSE00003749386	138773769	138773902

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 94.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0198 / max 130.8790, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70122	20.0198	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	94.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.83	gold quality
right adrenal gland	UBERON:0001233	94.76	gold quality
oocyte	CL:0000023	94.58	gold quality
pons	UBERON:0000988	94.13	gold quality
bronchial epithelial cell	CL:0002328	94.09	gold quality
left adrenal gland	UBERON:0001234	94.01	gold quality
left adrenal gland cortex	UBERON:0035825	93.75	gold quality
secondary oocyte	CL:0000655	93.70	gold quality
adrenal cortex	UBERON:0001235	93.68	gold quality
hypothalamus	UBERON:0001898	93.45	gold quality
right uterine tube	UBERON:0001302	93.42	gold quality
parotid gland	UBERON:0001831	93.41	gold quality
epithelium of bronchus	UBERON:0002031	93.16	gold quality
bronchus	UBERON:0002185	93.05	gold quality
nucleus accumbens	UBERON:0001882	93.02	gold quality
jejunal mucosa	UBERON:0000399	93.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.91	gold quality
renal medulla	UBERON:0000362	92.71	gold quality
Ammon’s horn	UBERON:0001954	92.64	gold quality
adrenal gland	UBERON:0002369	92.59	gold quality
nephron tubule	UBERON:0001231	92.58	gold quality
blood	UBERON:0000178	92.48	gold quality
body of pancreas	UBERON:0001150	92.41	gold quality
cingulate cortex	UBERON:0003027	92.38	gold quality
anterior cingulate cortex	UBERON:0009835	92.26	gold quality
right frontal lobe	UBERON:0002810	92.22	gold quality
adult mammalian kidney	UBERON:0000082	92.19	gold quality
nasal cavity mucosa	UBERON:0001826	92.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.86	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

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

92 targeting CCDC28A, 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-3064-3P	100.00	70.09	1254
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-497-5P	99.92	71.83	2674

Literature-anchored findings (GeneRIF, showing 1)

• the recurrent NUP98-CCDC28A is an oncogene that induces a rapid and transplantable myeloid neoplasm in recipient mice. They also provide additional evidence for an alternative leukemogenic mechanism for NUP98 oncogenes. (PMID:22058212)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc28a	ENSDARG00000022983
mus_musculus	Ccdc28a	ENSMUSG00000059554
rattus_norvegicus	Ccdc28a	ENSRNOG00000053347
drosophila_melanogaster	CG10874	FBGN0031395

Paralogs (1): CCDC28B (ENSG00000160050)

Protein

Protein identifiers

Coiled-coil domain-containing protein 28A — Q8IWP9 (reviewed: Q8IWP9)

Alternative names: CCRL1AP

All UniProt accessions (1): B4DUJ5

UniProt curated annotations — full annotation on UniProt →

Disease relevance. A chromosomal aberration involving CCDC28A has been identified in acute leukemias. Translocation t(6;11)(q24.1;p15.5) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 13 to CCDC28A exon 2. Ectopic expression of NUP98-CCDC28A in mouse promotes the proliferative capacity and self-renewal potential of hematopoietic progenitors and rapidly induced fatal myeloproliferative neoplasms and defects in the differentiation of the erythro-megakaryocytic lineage.

RefSeq proteins (1): NP_056254* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025271	CCDC28	Family

Pfam: PF13270

UniProt features (7 total): sequence variant 2, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWP9-F1	62.27	0.05

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 76–77 (breakpoint for translocation to form nup98-ccdc28a)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 167 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GGTGTGT_MIR329, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, VETTER_TARGETS_OF_PRKCA_AND_ETS1_DN, MODULE_205, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, TGAGATT_MIR216, TGCCTTA_MIR124A, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, TCCCRNNRTGC_UNKNOWN, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, SCGGAAGY_ELK1_02, STAT5A_02, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC28A	NUP98	P52948	636
CCDC28A	ECT2L	Q008S8	530
CCDC28A	ZMYND19	Q96E35	430
CCDC28A	CFAP77	Q6ZQR2	418
CCDC28A	RAP1GDS1	P52306	411
CCDC28A	LDAF1	Q96B96	400
CCDC28A	TMEM256	Q8N2U0	389
CCDC28A	KRABD2	Q6ZNG9	380
CCDC28A	TTC14	Q96N46	374
CCDC28A	TMEM168	Q9H0V1	373
CCDC28A	C5orf15	Q8NC54	370
CCDC28A	RSRC2	Q7L4I2	365
CCDC28A	UBFD1	O14562	362
CCDC28A	PRPSAP1	Q14558	360
CCDC28A	TMEM140	Q9NV12	357

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CCDC28A	MYOG	psi-mi:“MI:0915”(physical association)	0.670
CCDC28A	ICA1	psi-mi:“MI:0915”(physical association)	0.560
CCDC28A	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-2	CCDC28A	psi-mi:“MI:0915”(physical association)	0.560
CCDC28A	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
KIFC3	CCDC28A	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	CCDC28A	psi-mi:“MI:0915”(physical association)	0.560
CCDC28A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CCDC28A	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
rep	PSMD9	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100A4	VWA8	psi-mi:“MI:0914”(association)	0.350
CCDC28A	BLTP1	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
NFKBIB	CCDC28A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): CCDC28A (Two-hybrid), CCDC28A (Two-hybrid), CCDC28A (Two-hybrid), TRIM54 (Two-hybrid), KRTAP9-2 (Two-hybrid), CCDC28A (Affinity Capture-MS), CCDC28A (Affinity Capture-MS), CCDC28A (Affinity Capture-MS), CCDC28A (Affinity Capture-MS), CCDC28A (Affinity Capture-MS), CCDC28A (Affinity Capture-MS), DYNLL1 (Two-hybrid), MYOG (Two-hybrid), USHBP1 (Two-hybrid), IGFBP6 (Two-hybrid)

ESM2 similar proteins: A0A8I5KY20, A4IHR5, A7UKY7, A8IHN8, D3YYI7, G3V9M2, O43559, P39881, P49796, Q13387, Q14DQ1, Q2TAM9, Q32KV8, Q3UPL5, Q4VA45, Q5VUJ9, Q5VV17, Q5XKK7, Q62392, Q673H1, Q6NV74, Q6PJ61, Q6QHK4, Q6UXB0, Q7Z6J2, Q80TE3, Q86SH2, Q8BWU3, Q8CE64, Q8IWP9, Q8N554, Q8NFT6, Q8R4T5, Q8TC41, Q8VCC6, Q8WV24, Q96HA4, Q96IQ9, Q96SQ7, Q96T92

Diamond homologs: Q8CEG5, Q8IWP9, Q9BUN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
6:138773900:CAGGT:C	donor_loss	1.0000
6:138773901:AGGT:A	donor_loss	1.0000
6:138773902:GGT:G	donor_loss	1.0000
6:138773903:G:GA	donor_loss	1.0000
6:138779816:TTACA:T	acceptor_loss	1.0000
6:138779817:TACA:T	acceptor_loss	1.0000
6:138779819:CAGAG:C	acceptor_loss	1.0000
6:138779820:A:AG	acceptor_gain	1.0000
6:138779820:AGAG:A	acceptor_loss	1.0000
6:138779820:AGAGT:A	acceptor_gain	1.0000
6:138779821:G:GG	acceptor_gain	1.0000
6:138779821:G:T	acceptor_loss	1.0000
6:138779821:GA:G	acceptor_gain	1.0000
6:138779821:GAGT:G	acceptor_gain	1.0000
6:138779821:GAGTG:G	acceptor_gain	1.0000
6:138779982:TTTG:T	donor_gain	1.0000
6:138779982:TTTGG:T	donor_loss	1.0000
6:138779984:TGG:T	donor_loss	1.0000
6:138779986:G:GC	donor_loss	1.0000
6:138779986:G:GG	donor_gain	1.0000
6:138779987:T:A	donor_loss	1.0000
6:138785225:A:G	acceptor_gain	1.0000
6:138785378:AGAT:A	donor_gain	1.0000
6:138785378:AGATG:A	donor_loss	1.0000
6:138785379:GAT:G	donor_gain	1.0000
6:138785379:GATG:G	donor_gain	1.0000
6:138785380:AT:A	donor_gain	1.0000
6:138785380:ATGTA:A	donor_loss	1.0000
6:138785381:TGTA:T	donor_loss	1.0000
6:138785382:G:GG	donor_gain	1.0000

AlphaMissense

1206 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:138779958:T:C	F189L	1.000
6:138779960:C:A	F189L	1.000
6:138779960:C:G	F189L	1.000
6:138779982:T:C	F197L	1.000
6:138779984:T:A	F197L	1.000
6:138779984:T:G	F197L	1.000
6:138779895:T:C	F168L	0.999
6:138779897:C:A	F168L	0.999
6:138779897:C:G	F168L	0.999
6:138779938:T:C	L182P	0.999
6:138779947:T:C	L185P	0.999
6:138779959:T:C	F189S	0.999
6:138779959:T:G	F189C	0.999
6:138779974:T:A	L194H	0.999
6:138779974:T:C	L194P	0.999
6:138779983:T:G	F197C	0.999
6:138779938:T:A	L182Q	0.998
6:138779950:T:C	L186S	0.998
6:138779968:G:T	G192V	0.998
6:138779983:T:C	F197S	0.998
6:138785260:T:A	V209D	0.998
6:138785273:G:C	Q213H	0.998
6:138785273:G:T	Q213H	0.998
6:138788376:T:C	L253S	0.998
6:138779896:T:C	F168S	0.997
6:138779896:T:G	F168C	0.997
6:138779927:G:A	M178I	0.997
6:138779927:G:C	M178I	0.997
6:138779927:G:T	M178I	0.997
6:138779929:A:T	E179V	0.997

dbSNP variants (sampled 300 via entrez): RS1000283009 (6:138777739 A>C), RS1000366099 (6:138790131 C>T), RS1000374264 (6:138791428 G>A), RS1000833812 (6:138790259 T>C), RS1001061347 (6:138771880 AG>A), RS1001140740 (6:138790763 A>G), RS1001141879 (6:138784438 C>T), RS1001421938 (6:138790476 T>G), RS1001441389 (6:138774128 C>A,G,T), RS1001698607 (6:138783742 A>G), RS1001866291 (6:138779603 C>G), RS1001897352 (6:138772347 A>T), RS1001955373 (6:138793406 A>G), RS1002019705 (6:138786517 T>C), RS1002064125 (6:138778301 T>A,C)

Disease associations

OMIM: gene MIM:615353 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
graphene oxide	increases expression	2
sodium arsenite	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	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
Acetaminophen	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis