CCDC34

Summary

CCDC34 (coiled-coil domain containing 34, HGNC:25079) is a protein-coding gene on chromosome 11p14.1, encoding Coiled-coil domain-containing protein 34 (Q96HJ3). Involved in spermatogenesis.

Involved in spermatogenesis. Located in sperm midpiece. Implicated in spermatogenic failure 76.

Source: NCBI Gene 91057 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 76 (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 52 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_030771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25079
Approved symbol	CCDC34
Name	coiled-coil domain containing 34
Location	11p14.1
Locus type	gene with protein product
Status	Approved
Aliases	NY-REN-41, L15, RAMA3
Ensembl gene	ENSG00000109881
Ensembl biotype	protein_coding
OMIM	612324
Entrez	91057

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000317945, ENST00000328697, ENST00000529615, ENST00000860244, ENST00000930610

RefSeq mRNA: 2 — MANE Select: NM_030771 NM_030771, NM_080654

CCDS: CCDS31448, CCDS7863

Canonical transcript exons

ENST00000328697 — 6 exons

Exon	Start	End
ENSE00001218588	27357403	27357541
ENSE00001777717	27338512	27339035
ENSE00002201063	27362836	27363215
ENSE00002249132	27350332	27350439
ENSE00003515987	27340696	27340837
ENSE00003617235	27341392	27341550

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 94.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3315 / max 450.2721, expressed in 1639 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119057	9.1498	1526
119056	2.5148	1043
119054	0.8364	355
119055	0.7772	422
119050	0.0534	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.52	gold quality
right testis	UBERON:0004534	94.01	gold quality
testis	UBERON:0000473	93.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.89	gold quality
right uterine tube	UBERON:0001302	91.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.61	gold quality
ventricular zone	UBERON:0003053	89.63	gold quality
sperm	CL:0000019	88.60	gold quality
bronchial epithelial cell	CL:0002328	86.60	gold quality
ganglionic eminence	UBERON:0004023	85.90	gold quality
rectum	UBERON:0001052	85.83	gold quality
bronchus	UBERON:0002185	85.62	gold quality
ileal mucosa	UBERON:0000331	85.58	gold quality
buccal mucosa cell	CL:0002336	85.23	gold quality
nucleus accumbens	UBERON:0001882	84.82	gold quality
anterior cingulate cortex	UBERON:0009835	84.33	gold quality
cortical plate	UBERON:0005343	84.29	gold quality
caudate nucleus	UBERON:0001873	84.07	gold quality
middle temporal gyrus	UBERON:0002771	83.92	gold quality
trabecular bone tissue	UBERON:0002483	83.30	gold quality
putamen	UBERON:0001874	83.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.97	silver quality
epithelium of nasopharynx	UBERON:0001951	82.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.79	gold quality
left ventricle myocardium	UBERON:0006566	82.68	silver quality
Brodmann (1909) area 9	UBERON:0013540	82.50	gold quality
thymus	UBERON:0002370	82.44	gold quality
mucosa of transverse colon	UBERON:0004991	82.34	gold quality
prefrontal cortex	UBERON:0000451	82.09	gold quality
neocortex	UBERON:0001950	81.98	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	37.25
E-GEOD-134144	yes	28.21
E-GEOD-125970	yes	21.99
E-HCAD-13	yes	20.13
E-CURD-114	yes	11.13
E-ANND-3	yes	7.29
E-MTAB-9388	no	8.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting CCDC34, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-7705	98.69	67.47	543
HSA-MIR-3136-5P	98.53	67.68	793

Literature-anchored findings (GeneRIF, showing 7)

• CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration. (PMID:26312564)
• the present study demonstrated increased expression of CCDC34 protein in CRC tissues was associated with reduced apoptosis and increased metastasis in CRC cell line. (PMID:29115580)
• Immunohistochemistry showed that expression levels of CCDC34 protein in pancreatic adenocarcinoma were significantly increased, compared with normal pancreas (P=0.000). Patients with pancreatic adenocarcinoma with increased expression of tissue CCDC34 had significantly reduced OS compared with patients with low expression (P=0.000). (PMID:29257799)
• CCDC34 is overexpressed in esophageal squamous cell carcinoma. (PMID:29397026)
• Immunochemical staining data showed that CCDC34 expression was dramatically higher in CC than in adjacent normal tissues (71.6 vs. 20.9%; P<0.001). High expression of CCDC34 was strongly associated with histological grade (P=0.022), lymph node metastasis (P=0.044), and FIGO stage (P=0.002). (PMID:30458457)
• Homozygous mutations in CCDC34 cause male infertility with oligoasthenoteratozoospermia in humans and mice. (PMID:34348960)
• RABL2A-CCDC34 Axis Promotes Sorafenib Resistance in Hepatocellular Carcinoma. (PMID:34767735)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc34	ENSDARG00000098911
		ENSDARG00000102725
mus_musculus	Ccdc34	ENSMUSG00000027160
rattus_norvegicus	Ccdc34	ENSRNOG00000005902
drosophila_melanogaster	CG14011	FBGN0031722
drosophila_melanogaster	CG7251	FBGN0031723
drosophila_melanogaster	CG18266	FBGN0031724

Protein

Protein identifiers

Coiled-coil domain-containing protein 34 — Q96HJ3 (reviewed: Q96HJ3)

Alternative names: Renal carcinoma antigen NY-REN-41

All UniProt accessions (1): Q96HJ3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in spermatogenesis. Has a probable role in anterograde intraflagellar transport which is essential for the formation of sperm flagella.

Subcellular location. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in sperm.

Disease relevance. Spermatogenic failure 76 (SPGF76) [MIM:620084] An autosomal recessive male infertility disorder characterized by oligoasthenoteratozoospermia, and abnormally shaped spermatozoa in the semen of affected individuals. Sperm flagella have multiple morphological abnormalities, including short, absent, and irregular caliber flagella. The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving CCDC34 is found in a patient with hamartoma of the retinal pigment epithelium and retina. Translocation t(11;18) (p13;p11.2).

Miscellaneous. Antigen recognized by autologous antibody in patients with renal-cell carcinoma.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96HJ3-1	1	yes
Q96HJ3-2	2

RefSeq proteins (2): NP_110398, NP_542385 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025259	CCDC34/181	Domain
IPR045323	CCDC34	Family

Pfam: PF13904

UniProt features (16 total): sequence variant 4, region of interest 3, compositionally biased region 3, splice variant 2, chain 1, sequence conflict 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HJ3-F1	70.46	0.39

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): 52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MALE_GAMETE_GENERATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, FISCHER_DREAM_TARGETS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, GOCC_MOTILE_CILIUM, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_SPERM_MIDPIECE, MILI_PSEUDOPODIA, GOCC_CILIUM, chr11p14, DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP

GO Biological Process (1): spermatogenesis (GO:0007283)

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

GO Cellular Component (4): sperm midpiece (GO:0097225), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
binding	1
sperm flagellum	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC34	LIN7C	Q9NUP9	618
CCDC34	CCDC106	Q9BWC9	604
CCDC34	LGR4	Q9BXB1	582
CCDC34	CCDC150	Q8NCX0	530
CCDC34	CCDC77	Q9BR77	500
CCDC34	FAM216A	Q8WUB2	497
CCDC34	CCDC192	P0DO97	479
CCDC34	NEMP1	O14524	475
CCDC34	CEP85	Q6P2H3	471
CCDC34	CCDC8	Q9H0W5	471
CCDC34	DEPDC1B	Q8WUY9	460
CCDC34	REEP4	Q9H6H4	458
CCDC34	CCDC178	Q5BJE1	453
CCDC34	GSTCD	Q8NEC7	452
CCDC34	CCDC43	Q96MW1	440

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CCDC34	ACTBL2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): RABL2A (Affinity Capture-MS), RABL2A (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), CCDC34 (Affinity Capture-RNA), ADCK3 (Two-hybrid), TMEM86B (Two-hybrid), FAM76B (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), RABL2A (Affinity Capture-MS), CCDC34 (Affinity Capture-MS), CCDC34 (Positive Genetic), CCDC34 (Affinity Capture-RNA), CCDC34 (Proximity Label-MS), CCDC34 (Cross-Linking-MS (XL-MS)), DYNC1H1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A6H8Z2, A8T6P4, B0S4Q5, D3Z6S9, F1N4E5, F6QRE9, O35181, P0DJG4, P56950, P56975, Q05C16, Q13772, Q2KJH5, Q5FWP7, Q5JTV8, Q5PQN4, Q5PQR6, Q5PQX1, Q5R7A3, Q5RC32, Q5RD75, Q5U4H9, Q5W0A0, Q5XHX8, Q5XI03, Q5XX13, Q62187, Q66H34, Q66HD8, Q68D51, Q6A098, Q6ZPR1, Q7L0X2, Q7Z7G1, Q802X2, Q80VH0, Q8BVV7, Q8C627, Q8NDB2, Q96GE4

Diamond homologs: Q3UI66, Q96HJ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1710909	NM_030771.2(CCDC34):c.731dup (p.Asn244fs)	Pathogenic
1710910	NM_030771.2(CCDC34):c.799_817del (p.Glu267fs)	Pathogenic
4849401	NM_030771.2(CCDC34):c.615_619delAGAAA	Likely pathogenic

SpliceAI

391 predictions. Top by Δscore:

Variant	Effect	Δscore
11:27362859:T:A	donor_gain	1.0000
11:27362914:T:TA	donor_gain	1.0000
11:27350449:T:C	acceptor_gain	0.9900
11:27350449:T:TC	acceptor_gain	0.9900
11:27357397:TTTTA:T	donor_loss	0.9900
11:27357398:TTTA:T	donor_loss	0.9900
11:27357399:TTAC:T	donor_loss	0.9900
11:27357400:TA:T	donor_loss	0.9900
11:27357401:A:T	donor_loss	0.9900
11:27357402:C:A	donor_loss	0.9900
11:27362832:TTAC:T	donor_loss	0.9900
11:27362833:TACC:T	donor_loss	0.9900
11:27362855:C:CA	donor_gain	0.9900
11:27357402:CCT:C	donor_gain	0.9800
11:27362780:A:C	donor_gain	0.9800
11:27350437:TTCC:T	acceptor_loss	0.9700
11:27350438:TCCTG:T	acceptor_loss	0.9700
11:27350439:CCTGT:C	acceptor_loss	0.9700
11:27350440:C:CG	acceptor_loss	0.9700
11:27350441:T:G	acceptor_loss	0.9700
11:27350447:T:TC	acceptor_gain	0.9700
11:27350453:T:C	acceptor_gain	0.9700
11:27357537:GAGTG:G	acceptor_gain	0.9700
11:27362779:A:AC	donor_gain	0.9700
11:27362843:ACC:A	donor_gain	0.9700
11:27362844:CCC:C	donor_gain	0.9700
11:27350447:T:C	acceptor_gain	0.9600
11:27357541:GC:G	acceptor_loss	0.9600
11:27357542:CTACA:C	acceptor_loss	0.9600
11:27350453:T:TC	acceptor_gain	0.9500

AlphaMissense

2470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:27338982:A:G	W321R	0.998
11:27338982:A:T	W321R	0.998
11:27340768:A:G	W279R	0.996
11:27340768:A:T	W279R	0.996
11:27350353:C:A	W195C	0.996
11:27350353:C:G	W195C	0.996
11:27340766:C:A	W279C	0.995
11:27340766:C:G	W279C	0.995
11:27350355:A:G	W195R	0.995
11:27350355:A:T	W195R	0.995
11:27341442:A:G	W239R	0.994
11:27341442:A:T	W239R	0.994
11:27357466:C:A	W145C	0.994
11:27357466:C:G	W145C	0.994
11:27357468:A:G	W145R	0.994
11:27357468:A:T	W145R	0.994
11:27338980:C:A	W321C	0.993
11:27338980:C:G	W321C	0.993
11:27340775:A:C	F276L	0.993
11:27340775:A:T	F276L	0.993
11:27340777:A:G	F276L	0.993
11:27341440:C:A	W239C	0.993
11:27341440:C:G	W239C	0.993
11:27357459:A:G	W148R	0.993
11:27357459:A:T	W148R	0.993
11:27338998:A:C	F315L	0.992
11:27338998:A:T	F315L	0.992
11:27339000:A:G	F315L	0.992
11:27357445:T:A	K152N	0.991
11:27357445:T:G	K152N	0.991

dbSNP variants (sampled 300 via entrez): RS1000147449 (11:27344175 TA>T,TAA), RS1000159123 (11:27341332 T>C,G), RS1000276507 (11:27341063 A>G), RS1000439990 (11:27343597 G>A), RS1000497902 (11:27339593 T>C), RS1000550183 (11:27338382 CT>C), RS1000613895 (11:27339218 A>T), RS1000861542 (11:27353362 T>A), RS1000895809 (11:27364194 A>C,G), RS1001063652 (11:27363109 G>A), RS1001197493 (11:27346095 T>A), RS1001306729 (11:27363753 G>T), RS1001403863 (11:27340575 T>G), RS1001440034 (11:27360118 C>T), RS1001467393 (11:27358406 A>G)

Disease associations

OMIM: gene MIM:612324 | disease phenotypes: MIM:620084

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 76	Limited	Unknown

Mondo (1): spermatogenic failure 76 (MONDO:0031077)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000798	Oligozoospermia
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0033393	Irregularly shaped sperm tail

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002493_1	Bone mineral density (paediatric, skull)	8.000000e-06
GCST006979_782	Heel bone mineral density	6.000000e-15
GCST006979_783	Heel bone mineral density	1.000000e-25
GCST008128_3	Body mass index	2.000000e-07
GCST008151_117	Waist circumference	3.000000e-06
GCST008160_69	Waist circumference	3.000000e-06
GCST009267_13	Dental caries (decayed, missing and filled teeth)	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
cinnamaldehyde	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
belinostat	increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
NSC 689534	affects binding, decreases expression	1

Clinical trials (associated diseases)

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