CCDC74A

Summary

CCDC74A (coiled-coil domain containing 74A, HGNC:25197) is a protein-coding gene on chromosome 2q21.1, encoding Coiled-coil domain-containing protein 74A (Q96AQ1).

At a glance

• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_001258306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25197
Approved symbol	CCDC74A
Name	coiled-coil domain containing 74A
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40345
Ensembl gene	ENSG00000163040
Ensembl biotype	protein_coding
Entrez	90557

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 22 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000295171, ENST00000409856, ENST00000434330, ENST00000454549, ENST00000465939, ENST00000467992, ENST00000468650, ENST00000478665, ENST00000899928, ENST00000899929, ENST00000899930, ENST00000899931, ENST00000899932, ENST00000899933, ENST00000899934, ENST00000899935, ENST00000899936, ENST00000912825, ENST00000912826, ENST00000944304, ENST00000944305, ENST00000944306, ENST00000944307, ENST00000944308, ENST00000944309, ENST00000944310

RefSeq mRNA: 11 — MANE Select: NM_001258306 NM_001258304, NM_001258305, NM_001258306, NM_001349041, NM_001349042, NM_001349043, NM_001349044, NM_001349045, NM_001349046, NM_001349047, NM_138770

CCDS: CCDS2167, CCDS58732, CCDS74578

Canonical transcript exons

ENST00000409856 — 8 exons

Exon	Start	End
ENSE00001810086	131533269	131533666
ENSE00001927403	131527888	131528220
ENSE00002451716	131532589	131532781
ENSE00002462476	131530777	131530827
ENSE00002510964	131531664	131531802
ENSE00003493798	131533013	131533069
ENSE00003505117	131529647	131529691
ENSE00003526843	131532864	131532937

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.8861 / max 54.2742, expressed in 1040 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
202396	1.8861	1040

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.26	gold quality
right testis	UBERON:0004534	96.06	gold quality
left testis	UBERON:0004533	96.01	gold quality
testis	UBERON:0000473	95.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.82	gold quality
pituitary gland	UBERON:0000007	92.21	gold quality
right adrenal gland	UBERON:0001233	91.34	gold quality
left adrenal gland cortex	UBERON:0035825	91.08	gold quality
right adrenal gland cortex	UBERON:0035827	91.03	gold quality
left adrenal gland	UBERON:0001234	90.84	gold quality
adenohypophysis	UBERON:0002196	90.76	gold quality
ventricular zone	UBERON:0003053	89.29	gold quality
adrenal gland	UBERON:0002369	88.26	gold quality
stromal cell of endometrium	CL:0002255	87.79	gold quality
fallopian tube	UBERON:0003889	87.47	gold quality
nucleus accumbens	UBERON:0001882	85.31	gold quality
hypothalamus	UBERON:0001898	85.15	gold quality
endocervix	UBERON:0000458	84.69	gold quality
temporal lobe	UBERON:0001871	83.64	gold quality
amygdala	UBERON:0001876	83.64	gold quality
caudate nucleus	UBERON:0001873	83.46	gold quality
left ovary	UBERON:0002119	83.40	gold quality
Ammon’s horn	UBERON:0001954	83.18	gold quality
body of uterus	UBERON:0009853	82.88	gold quality
right ovary	UBERON:0002118	82.54	gold quality
prostate gland	UBERON:0002367	82.44	gold quality
putamen	UBERON:0001874	82.41	gold quality
ovary	UBERON:0000992	82.35	gold quality
myometrium	UBERON:0001296	81.79	gold quality
right frontal lobe	UBERON:0002810	80.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	12.11
E-ANND-3	yes	10.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting CCDC74A, 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-6508-5P	99.92	70.67	2465
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-8067	99.86	69.59	2260
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
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-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-4683	95.29	65.98	631

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): CCDC74B (ENSG00000152076)

Protein

Protein identifiers

Coiled-coil domain-containing protein 74A — Q96AQ1 (reviewed: Q96AQ1)

All UniProt accessions (5): Q96AQ1, A0A384MR57, C9IYK9, F5GZA4, F8WEI8

Isoforms (2)

UniProt ID	Names	Canonical?
Q96AQ1-1	1	yes
Q96AQ1-2	2

RefSeq proteins (11): NP_001245233, NP_001245234, NP_001245235, NP_001335970, NP_001335971, NP_001335972, NP_001335973, NP_001335974, NP_001335975, NP_001335976, NP_620125 (=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 (12 total): compositionally biased region 5, region of interest 3, chain 1, splice variant 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AQ1-F1	60.87	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, RFX1_02, CERVERA_SDHB_TARGETS_1_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, ZNF146_TARGET_GENES, ZNF407_TARGET_GENES, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2, MIR12131, BLANCO_MELO_BRONCHIAL_EPITHELIAL_CELLS_INFLUENZA_A_INFECTION_DN, MEBARKI_HCC_PROGENITOR_FZD8CRD_UP, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, GAO_LARGE_INTESTINE_ADULT_CA_ENTEROENDOCRINE_CELLS, GAO_LARGE_INTESTINE_ADULT_CH_MKI67HIGH_CELLS, MURARO_PANCREAS_MESENCHYMAL_STROMAL_CELL

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

192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC74A	OR2T35	Q8NGX2	507
CCDC74A	CFAP57	Q96MR6	459
CCDC74A	ZNF248	Q8NDW4	445
CCDC74A	ZNF417	Q8TAU3	444
CCDC74A	SDSL	Q96GA7	437
CCDC74A	TLCD4	Q96MV1	437
CCDC74A	SMTNL2	Q2TAL5	401
CCDC74A	VWCE	Q96DN2	397
CCDC74A	RBMXL2	O75526	390
CCDC74A	SLC25A21	Q9BQT8	389
CCDC74A	REEP6	Q96HR9	382
CCDC74A	NOMO2	Q5JPE7	378
CCDC74A	ERCC6L	Q2NKX8	361
CCDC74A	SMCR8	Q8TEV9	358
CCDC74A	SDS	P20132	355
CCDC74A	SEC14L2	O76054	355

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CCDC74A	CEP19	psi-mi:“MI:0915”(physical association)	0.560
ZNF655	CCDC74A	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	CCDC74A	psi-mi:“MI:0915”(physical association)	0.370
KDM1A	CCDC74A	psi-mi:“MI:0915”(physical association)	0.370
CCDC74A	PSMD11	psi-mi:“MI:0914”(association)	0.350
CEP19	CCDC74A	psi-mi:“MI:0915”(physical association)	0.000
CCDC74A	ZNF655	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): CCDC74A (Two-hybrid), CEP19 (Two-hybrid), ZNF655 (Two-hybrid), MAN2B2 (Affinity Capture-MS), THNSL1 (Affinity Capture-MS), CEP76 (Affinity Capture-MS), LIN9 (Affinity Capture-MS), CCDC74B (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), LIN54 (Affinity Capture-MS), PSMC2 (Affinity Capture-MS), UCHL5 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), PSMC6 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	16
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1607 predictions. Top by Δscore:

Variant	Effect	Δscore
2:131528219:GG:G	donor_gain	1.0000
2:131528220:GG:G	donor_gain	1.0000
2:131531799:CCAG:C	donor_loss	1.0000
2:131531800:CAGG:C	donor_loss	1.0000
2:131531801:AGG:A	donor_loss	1.0000
2:131531802:GG:G	donor_loss	1.0000
2:131531804:T:A	donor_loss	1.0000
2:131532863:GCTGC:G	acceptor_gain	1.0000
2:131532921:G:GT	donor_gain	1.0000
2:131532934:CCAGG:C	donor_loss	1.0000
2:131532936:AGGTG:A	donor_loss	1.0000
2:131532939:T:G	donor_loss	1.0000
2:131533008:C:G	acceptor_gain	1.0000
2:131533008:CCCA:C	acceptor_loss	1.0000
2:131533011:A:AG	acceptor_gain	1.0000
2:131533011:AG:A	acceptor_gain	1.0000
2:131533011:AGG:A	acceptor_gain	1.0000
2:131533012:G:GG	acceptor_gain	1.0000
2:131533012:GG:G	acceptor_gain	1.0000
2:131533012:GGG:G	acceptor_gain	1.0000
2:131533065:AAATG:A	donor_gain	1.0000
2:131533066:AATG:A	donor_gain	1.0000
2:131533067:ATG:A	donor_gain	1.0000
2:131533067:ATGG:A	donor_loss	1.0000
2:131533068:TG:T	donor_gain	1.0000
2:131533069:GG:G	donor_gain	1.0000
2:131533070:G:GA	donor_loss	1.0000
2:131533070:G:GG	donor_gain	1.0000
2:131533265:CCAGC:C	acceptor_loss	1.0000
2:131533266:CAGCC:C	acceptor_loss	1.0000

AlphaMissense

2042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:131528145:T:C	F59L	0.996
2:131528147:C:A	F59L	0.996
2:131528147:C:G	F59L	0.996
2:131528149:T:C	L60P	0.995
2:131528182:T:C	L71P	0.995
2:131528203:T:C	L78P	0.995
2:131528140:T:C	L57P	0.991
2:131528158:A:C	Q63P	0.991
2:131528146:T:C	F59S	0.989
2:131528209:G:C	R80P	0.989
2:131532750:T:C	L282P	0.989
2:131528152:A:C	Q61P	0.986
2:131528163:T:C	S65P	0.986
2:131528161:A:C	H64P	0.985
2:131529662:T:C	L89P	0.985
2:131528207:G:C	K79N	0.984
2:131528207:G:T	K79N	0.984
2:131529650:T:C	L85P	0.984
2:131528160:C:G	H64D	0.983
2:131532874:T:C	L296P	0.983
2:131528146:T:G	F59C	0.981
2:131528191:A:T	E74V	0.981
2:131532741:T:C	I279T	0.981
2:131532865:T:C	L293P	0.979
2:131528182:T:A	L71H	0.978
2:131528155:A:C	Q62P	0.975
2:131528128:T:C	L53P	0.973
2:131528173:T:C	L68P	0.969
2:131532741:T:G	I279S	0.965
2:131532741:T:A	I279N	0.964

dbSNP variants (sampled 300 via entrez): RS1000093579 (2:131528753 G>A), RS1000327009 (2:131523228 T>C), RS1001467411 (2:131523834 A>G), RS1001527348 (2:131529327 A>C,G), RS1001641853 (2:131529136 T>G), RS1001980464 (2:131527888 A>G), RS1002161026 (2:131533195 G>C), RS1002451070 (2:131533289 A>G,T), RS1002530375 (2:131530184 T>A,C), RS1003993792 (2:131525497 C>T), RS1005044555 (2:131520975 A>G), RS1005715829 (2:131523055 C>A), RS1006142831 (2:131521978 A>G), RS1006222492 (2:131527186 T>C), RS1006223582 (2:131522840 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:192350

GenCC curated gene-disease

Mondo (1): VACTERL/vater association (MONDO:0008642)

Orphanet (1): VACTERL/VATER association (Orphanet:887)

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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, affects expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
beta-lapachone	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
aflatoxin B2	increases methylation	1
abrine	decreases expression	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Phenylmercuric Acetate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
p-Chloromercuribenzoic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03799705	Not specified	COMPLETED	Genetic Variants in Nicotinamide Adenine Dinucleotide (NAD) Synthesis Pathway