CCDC74B

Summary

CCDC74B (coiled-coil domain containing 74B, HGNC:25267) is a protein-coding gene on chromosome 2q21.1, encoding Coiled-coil domain-containing protein 74B (Q96LY2). It is a selective cancer dependency (DepMap: 11.5% of cell lines).

At a glance

• Clinical variants (ClinVar): 111 total
• Cancer dependency (DepMap): dependent in 11.5% of screened cell lines
• MANE Select transcript: NM_001258307

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25267
Approved symbol	CCDC74B
Name	coiled-coil domain containing 74B
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434E2321
Ensembl gene	ENSG00000152076
Ensembl biotype	protein_coding
Entrez	91409

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000310463, ENST00000392984, ENST00000409128, ENST00000409234, ENST00000409943, ENST00000423263, ENST00000434929, ENST00000441670, ENST00000457413, ENST00000496704, ENST00000498526, ENST00000860852, ENST00000860853, ENST00000860854, ENST00000860855, ENST00000860856, ENST00000860857, ENST00000944366, ENST00000944367, ENST00000944368

RefSeq mRNA: 2 — MANE Select: NM_001258307 NM_001258307, NM_207310

CCDS: CCDS2155, CCDS58726

Canonical transcript exons

ENST00000409943 — 8 exons

Exon	Start	End
ENSE00001159038	130144747	130145112
ENSE00002512606	130140179	130140371
ENSE00002529714	130142133	130142183
ENSE00003548569	130141158	130141296
ENSE00003611507	130143269	130143313
ENSE00003632177	130139287	130139690
ENSE00003715929	130139891	130139947
ENSE00003737437	130140023	130140096

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 97.04.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.04	gold quality
left testis	UBERON:0004533	93.60	gold quality
right testis	UBERON:0004534	93.52	gold quality
testis	UBERON:0000473	93.00	gold quality
pituitary gland	UBERON:0000007	89.42	gold quality
adenohypophysis	UBERON:0002196	87.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.62	gold quality
endocervix	UBERON:0000458	84.93	gold quality
fallopian tube	UBERON:0003889	83.69	gold quality
stromal cell of endometrium	CL:0002255	82.95	gold quality
ventricular zone	UBERON:0003053	82.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.48	gold quality
body of uterus	UBERON:0009853	80.03	gold quality
right adrenal gland	UBERON:0001233	79.82	gold quality
hypothalamus	UBERON:0001898	79.55	gold quality
right adrenal gland cortex	UBERON:0035827	78.95	gold quality
left adrenal gland cortex	UBERON:0035825	78.77	gold quality
left adrenal gland	UBERON:0001234	78.41	gold quality
myometrium	UBERON:0001296	78.33	gold quality
prostate gland	UBERON:0002367	78.01	gold quality
right lobe of thyroid gland	UBERON:0001119	77.89	gold quality
left uterine tube	UBERON:0001303	77.84	gold quality
ectocervix	UBERON:0012249	77.58	gold quality
uterine cervix	UBERON:0000002	77.45	gold quality
thyroid gland	UBERON:0002046	77.30	gold quality
left lobe of thyroid gland	UBERON:0001120	77.21	gold quality
Ammon’s horn	UBERON:0001954	77.21	gold quality
left ovary	UBERON:0002119	76.68	gold quality
nucleus accumbens	UBERON:0001882	76.59	gold quality
adrenal gland	UBERON:0002369	76.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting CCDC74B, 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-223-3P	99.99	70.14	1140
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-890	97.47	68.67	982
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-4683	95.29	65.98	631

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• The authors characterized CCDC74A and CCDC74B as microtubule-associated proteins that localize to spindles and are important K-fiber crosslinkers required for bipolar spindle formation and chromosome alignment. (PMID:31521166)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc74a	ENSMUSG00000041617
rattus_norvegicus	Ccdc74a	ENSRNOG00000001876

Paralogs (1): CCDC74A (ENSG00000163040)

Protein

Protein identifiers

Coiled-coil domain-containing protein 74B — Q96LY2 (reviewed: Q96LY2)

All UniProt accessions (8): B8ZZB0, C9JC78, E7ESC5, E9PG54, Q96LY2, F8WB40, F8WCQ0, H7C1C8

Isoforms (2)

UniProt ID	Names	Canonical?
Q96LY2-1	1	yes
Q96LY2-2	2

RefSeq proteins (2): NP_001245236, NP_997193 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029422	CCDC74_C	Domain
IPR039496	CCDC92/74_N	Domain
IPR040370	CCDC74A/CCDC74B/CCDC92	Family

Pfam: PF14916, PF14917

UniProt features (11 total): region of interest 3, compositionally biased region 3, sequence variant 2, chain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LY2-F1	60.67	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, RFX1_02, SENGUPTA_EBNA1_ANTICORRELATED, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHYLA_CBFA2T3_TARGETS_DN, ZNF423_TARGET_GENES, MIR12131, MIR3659, BLANCO_MELO_RESPIRATORY_SYNCYTIAL_VIRUS_INFECTION_A594_CELLS_DN, VANTVEER_BREAST_CANCER_BRCA1_DN, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, GAO_LARGE_INTESTINE_ADULT_CA_ENTEROENDOCRINE_CELLS, VANTVEER_BREAST_CANCER_ESR1_UP, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC74B	LRRC63	Q05C16	668
CCDC74B	CCDC125	Q86Z20	624
CCDC74B	CCDC70	Q6NSX1	569
CCDC74B	ZNG1B	Q8IUF1	542
CCDC74B	SPATA31A1	Q5TZJ5	541
CCDC74B	CFAP184	Q2M329	531
CCDC74B	ANKRD60	Q9BZ19	528
CCDC74B	C12orf42	Q96LP6	524
CCDC74B	CCDC169	A6NNP5	476
CCDC74B	PHAF1	Q9BSU1	474
CCDC74B	FAM47C	Q5HY64	472
CCDC74B	TTLL8	A6PVC2	471
CCDC74B	CCDC190	Q86UF4	447
CCDC74B	ZNF287	Q9HBT7	447
CCDC74B	ZNF641	Q96N77	446

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CCDC74B	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
CCDC74B	PSMD11	psi-mi:“MI:0914”(association)	0.350
CCDC74A	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): PSMD1 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMC6 (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD14 (Affinity Capture-MS), ADRM1 (Affinity Capture-MS), PSMC2 (Affinity Capture-MS), THNSL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A6NDY2, A6NIJ5, A6NJQ4, A6NKC0, A6NNH2, A6NNJ1, A8MUA0, A8MWA6, A8MX19, A8MXJ8, A8MXZ1, A8MYA2, B1ASB6, D6RGX4, P0C7V4, P0C7W8, P0C7W9, P0C7X0, P0DV73, P0DV74, P0DV75, P0DV76, Q0VDD7, Q2KIS6, Q3UHD3, Q4R736, Q5SZB4, Q5T8A7, Q5VZ46, Q5XIK6, Q658T7, Q6A025, Q6NTE8, Q6PIX9, Q6ZMY3, Q86Y26, Q86YD7

Diamond homologs: Q96AQ1, Q96LY2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1654 predictions. Top by Δscore:

Variant	Effect	Δscore
2:130139686:GCAGG:G	acceptor_gain	1.0000
2:130139687:CAGG:C	acceptor_gain	1.0000
2:130139687:CAGGC:C	acceptor_gain	1.0000
2:130139688:AGG:A	acceptor_gain	1.0000
2:130139689:GG:G	acceptor_gain	1.0000
2:130139690:GCTG:G	acceptor_loss	1.0000
2:130139691:C:CC	acceptor_gain	1.0000
2:130139886:CTTA:C	donor_loss	1.0000
2:130139887:TTACC:T	donor_loss	1.0000
2:130139889:A:AC	donor_gain	1.0000
2:130139889:AC:A	donor_gain	1.0000
2:130139890:C:CA	donor_gain	1.0000
2:130139890:CC:C	donor_gain	1.0000
2:130139890:CCA:C	donor_gain	1.0000
2:130139890:CCAT:C	donor_gain	1.0000
2:130139890:CCATT:C	donor_gain	1.0000
2:130139944:GTCC:G	acceptor_gain	1.0000
2:130139945:TCC:T	acceptor_gain	1.0000
2:130139946:CC:C	acceptor_gain	1.0000
2:130139946:CCC:C	acceptor_gain	1.0000
2:130139947:CC:C	acceptor_gain	1.0000
2:130139948:C:A	acceptor_loss	1.0000
2:130139948:C:CC	acceptor_gain	1.0000
2:130139949:T:C	acceptor_loss	1.0000
2:130139952:G:C	acceptor_gain	1.0000
2:130140018:CTCA:C	donor_loss	1.0000
2:130140019:TCA:T	donor_loss	1.0000
2:130140020:CACC:C	donor_loss	1.0000
2:130140021:A:T	donor_loss	1.0000
2:130140022:C:CA	donor_loss	1.0000

AlphaMissense

2051 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:130144820:G:C	F59L	0.995
2:130144820:G:T	F59L	0.995
2:130144822:A:G	F59L	0.995
2:130144785:A:G	L71P	0.993
2:130144764:A:G	L78P	0.991
2:130140210:A:G	L282P	0.990
2:130144818:A:G	L60P	0.989
2:130140086:A:G	L296P	0.985
2:130144821:A:G	F59S	0.984
2:130144809:T:G	Q63P	0.983
2:130144827:A:G	L57P	0.983
2:130140095:A:G	L293P	0.982
2:130144804:A:G	S65P	0.978
2:130140219:A:G	I279T	0.977
2:130144815:T:G	Q61P	0.977
2:130144758:C:G	R80P	0.976
2:130144821:A:C	F59C	0.975
2:130144806:T:G	H64P	0.974
2:130144785:A:T	L71H	0.972
2:130144807:G:C	H64D	0.972
2:130144812:T:G	Q62P	0.970
2:130140195:A:G	L287P	0.967
2:130140189:T:G	Q289P	0.966
2:130143310:A:G	L85P	0.964
2:130144794:A:G	L68P	0.964
2:130143298:A:G	L89P	0.963
2:130144776:T:A	E74V	0.963
2:130140197:G:C	N286K	0.962
2:130140197:G:T	N286K	0.962
2:130140219:A:T	I279N	0.961

dbSNP variants (sampled 300 via entrez): RS1000626450 (2:130144417 G>A,C), RS1001733485 (2:130144752 T>G), RS1001975360 (2:130139280 A>C), RS1002034526 (2:130145590 A>G), RS1002064001 (2:130145977 A>G), RS1002238795 (2:130139985 G>T), RS1003539368 (2:130142052 T>C), RS1003697315 (2:130146935 T>C), RS1004225460 (2:130146246 C>T), RS1005379018 (2:130143557 G>A), RS1005484094 (2:130142870 C>A,T), RS1005902637 (2:130143924 G>A,T), RS1007544053 (2:130144002 G>C), RS1007616048 (2:130144201 A>G), RS1007875860 (2:130144995 A>C,G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Arsenic	decreases expression, increases abundance, affects cotreatment	3
Smoke	decreases expression, increases abundance, increases expression	2
sodium arsenate	decreases expression, increases abundance	1
terbufos	increases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
abrine	decreases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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