CCDC38

Summary

CCDC38 (coiled-coil domain containing 38, HGNC:26843) is a protein-coding gene on chromosome 12q23.1, encoding Coiled-coil domain-containing protein 38 (Q502W7). Essential for male fertility.

Predicted to enable ubiquitin-modified histone reader activity. Predicted to be involved in acrosome assembly and sperm flagellum assembly. Located in centrosome.

Source: NCBI Gene 120935 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_182496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26843
Approved symbol	CCDC38
Name	coiled-coil domain containing 38
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40089
Ensembl gene	ENSG00000165972
Ensembl biotype	protein_coding
Entrez	120935

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000344280, ENST00000546386, ENST00000546803, ENST00000546816, ENST00000546947, ENST00000548771, ENST00000549752, ENST00000549876

RefSeq mRNA: 1 — MANE Select: NM_182496 NM_182496

CCDS: CCDS9056

Canonical transcript exons

ENST00000344280 — 16 exons

Exon	Start	End
ENSE00001098534	95872255	95872460
ENSE00001098543	95881485	95881554
ENSE00001098549	95879644	95879795
ENSE00001098558	95878211	95878346
ENSE00001192670	95890832	95890930
ENSE00001192680	95898385	95898465
ENSE00001192685	95898568	95898731
ENSE00001192689	95906387	95906451
ENSE00001192691	95917129	95917294
ENSE00001192696	95867048	95867189
ENSE00001280476	95888458	95888506
ENSE00001310188	95894989	95895146
ENSE00002403811	95942431	95942614
ENSE00003462684	95869480	95869573
ENSE00003497405	95918876	95918976
ENSE00003573202	95936473	95936523

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 89.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0811 / max 49.6193, expressed in 11 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132756	0.0688	10
132755	0.0123	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	89.36	gold quality
right testis	UBERON:0004534	88.66	gold quality
testis	UBERON:0000473	86.45	gold quality
sperm	CL:0000019	84.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.56	gold quality
right lobe of liver	UBERON:0001114	75.13	gold quality
adrenal tissue	UBERON:0018303	74.59	gold quality
liver	UBERON:0002107	64.79	gold quality
epithelium of nasopharynx	UBERON:0001951	64.64	silver quality
sural nerve	UBERON:0015488	62.81	silver quality
calcaneal tendon	UBERON:0003701	62.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	62.19	gold quality
adult organism	UBERON:0007023	61.93	gold quality
germinal epithelium of ovary	UBERON:0001304	59.36	gold quality
spleen	UBERON:0002106	58.12	gold quality
lower lobe of lung	UBERON:0008949	56.21	silver quality
gingival epithelium	UBERON:0001949	55.29	gold quality
cerebellar hemisphere	UBERON:0002245	55.02	gold quality
cerebellar cortex	UBERON:0002129	54.98	gold quality
islet of Langerhans	UBERON:0000006	54.71	gold quality
adrenal gland	UBERON:0002369	54.71	gold quality
tendon	UBERON:0000043	54.31	gold quality
left adrenal gland cortex	UBERON:0035825	54.30	gold quality
right lung	UBERON:0002167	54.25	gold quality
cerebellum	UBERON:0002037	54.00	gold quality
left adrenal gland	UBERON:0001234	53.96	gold quality
bone marrow	UBERON:0002371	53.87	gold quality
right adrenal gland cortex	UBERON:0035827	53.43	gold quality
smooth muscle tissue	UBERON:0001135	53.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• strongest signal of association with smoking resistance for a non-synonymous SNP in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells (PMID:24786987)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc38	ENSMUSG00000036168
rattus_norvegicus	Ccdc38	ENSRNOG00000021892

Paralogs (3): CCDC42 (ENSG00000161973), CFAP100 (ENSG00000163885), CFAP73 (ENSG00000186710)

Protein

Protein identifiers

Coiled-coil domain-containing protein 38 — Q502W7 (reviewed: Q502W7)

All UniProt accessions (5): Q502W7, F8VRK3, F8VTU7, F8VY05, H0YHI1

UniProt curated annotations — full annotation on UniProt →

Function. Essential for male fertility. Required for sperm flagellum biogenesis. Also required for acrosome biogenesis. Required for the attachment of developing acrosomes to the nucleus during spermiogenesis and may be involved in the transport of fibrous sheath components.

Subunit / interactions. Interacts with CCDC42, CFAP53, IFT88 and ODF2. Interacts with CCDC146. Interacts with TEKT3. Interacts with ubiquitinated histone H2A.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Perinuclear region. Cell projection. Cilium. Flagellum.

RefSeq proteins (1): NP_872302* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025252	DUF4200	Domain
IPR051147	CFAP_domain-containing	Family

Pfam: PF13863

UniProt features (13 total): region of interest 3, coiled-coil region 3, compositionally biased region 3, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q502W7-F1	73.84	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): GOBP_VESICLE_ORGANIZATION, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOCC_CENTROSOME, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ACROSOME_ASSEMBLY

GO Biological Process (6): acrosome assembly (GO:0001675), intraciliary anterograde transport (GO:0035720), sperm flagellum assembly (GO:0120316), chromatin organization (GO:0006325), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (1): ubiquitin-modified histone reader activity (GO:0061649)

GO Cellular Component (10): manchette (GO:0002177), centrosome (GO:0005813), sperm flagellum (GO:0036126), perinuclear region of cytoplasm (GO:0048471), sperm head (GO:0061827), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), 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	5
developmental process involved in reproduction	3
spermatid development	2
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
intraciliary transport	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component organization	1
male gamete generation	1
cellular developmental process	1
ubiquitin-modified protein reader activity	1
histone reader activity	1
microtubule cytoskeleton	1
centriole	1
microtubule organizing center	1
9+2 motile cilium	1
cytoplasm	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC38	CCDC42	Q96M95	791
CCDC38	CFAP73	A6NFT4	632
CCDC38	SPATA9	Q9BWV2	624
CCDC38	ARMC2	Q8NEN0	605
CCDC38	CFAP184	Q2M329	591
CCDC38	SPMIP4	Q8N865	584
CCDC38	CFAP96	A7E2U8	580
CCDC38	CCDC116	Q8IYX3	541
CCDC38	LRMDA	Q9H2I8	512
CCDC38	CCDC146	Q8IYE0	509
CCDC38	SNRPF	P62306	498
CCDC38	CFDP1	Q9UEE9	485
CCDC38	ZKSCAN3	Q9BRR0	480
CCDC38	CFAP263	Q9H0I3	478
CCDC38	FAM13A	O94988	445

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CCDC38	PPIB	psi-mi:“MI:0915”(physical association)	0.400
CCDC38	GAPDH	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): CCDC38 (Affinity Capture-MS), CCDC38 (Proximity Label-MS), CCDC38 (Proximity Label-MS), EEA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GVH7, A0A4X1TZW7, A0A5F8MPE6, E1B836, E1C760, E7EXT2, F7AEX0, O74370, O95391, P21374, P51950, Q20716, Q24276, Q24740, Q28E45, Q2F5J3, Q2KI00, Q3B820, Q3KQD1, Q3TGF2, Q3ZBE5, Q45GW3, Q4R4P2, Q502W7, Q569B9, Q5EAW4, Q5RHY1, Q5U4F3, Q5XI37, Q5XIN9, Q5ZIG2, Q69ZQ2, Q6SP97, Q7L590, Q80ZG5, Q8BHJ9, Q8BRC6, Q8CDN8, Q8NCR3, Q8TC29

Diamond homologs: Q494V2, Q4R8V8, Q502W7, Q80VN0, Q8CDN8, Q95JL6, A8I4E9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2703 predictions. Top by Δscore:

Variant	Effect	Δscore
12:95867185:CCCAA:C	acceptor_gain	1.0000
12:95867186:CCAA:C	acceptor_gain	1.0000
12:95867186:CCAAC:C	acceptor_gain	1.0000
12:95867187:CAA:C	acceptor_gain	1.0000
12:95867187:CAAC:C	acceptor_gain	1.0000
12:95867188:AA:A	acceptor_gain	1.0000
12:95867188:AACTG:A	acceptor_loss	1.0000
12:95867189:ACTGA:A	acceptor_loss	1.0000
12:95867190:C:CC	acceptor_gain	1.0000
12:95867190:CTGAA:C	acceptor_loss	1.0000
12:95869475:CAAA:C	donor_loss	1.0000
12:95869476:AAACC:A	donor_loss	1.0000
12:95869477:AACC:A	donor_loss	1.0000
12:95869478:A:T	donor_loss	1.0000
12:95869571:AACC:A	acceptor_loss	1.0000
12:95869574:C:CC	acceptor_gain	1.0000
12:95869574:CTGT:C	acceptor_loss	1.0000
12:95869575:T:A	acceptor_loss	1.0000
12:95869578:C:CT	acceptor_gain	1.0000
12:95872238:AT:A	donor_gain	1.0000
12:95872253:A:AC	donor_gain	1.0000
12:95872254:C:CC	donor_gain	1.0000
12:95879642:A:AC	donor_gain	1.0000
12:95879643:C:CC	donor_gain	1.0000
12:95881495:T:TA	donor_gain	1.0000
12:95881555:C:CC	acceptor_gain	1.0000
12:95888552:G:GC	acceptor_gain	1.0000
12:95898461:CTGCC:C	acceptor_gain	1.0000
12:95898464:CC:C	acceptor_gain	1.0000
12:95898465:CC:C	acceptor_gain	1.0000

AlphaMissense

3748 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:95898578:C:G	A175P	0.997
12:95898609:G:C	F164L	0.996
12:95898609:G:T	F164L	0.996
12:95898611:A:G	F164L	0.996
12:95898421:A:G	L193P	0.994
12:95898604:C:G	R166P	0.992
12:95898607:A:G	L165P	0.992
12:95898618:A:C	F161L	0.992
12:95898618:A:T	F161L	0.992
12:95898620:A:G	F161L	0.992
12:95879779:A:G	F336S	0.991
12:95895090:A:G	L224P	0.991
12:95898439:A:G	L187P	0.991
12:95898413:C:G	A196P	0.990
12:95898464:C:G	A179P	0.990
12:95879725:A:G	L354P	0.989
12:95879740:A:G	L349P	0.989
12:95879778:G:C	F336L	0.989
12:95879778:G:T	F336L	0.989
12:95879780:A:G	F336L	0.989
12:95895120:A:G	L214P	0.989
12:95898461:C:G	A180P	0.989
12:95879761:A:G	L342S	0.988
12:95898629:C:G	A158P	0.987
12:95898640:A:G	L154P	0.984
12:95898653:C:G	A150P	0.984
12:95879731:T:G	Q352P	0.981
12:95895065:C:A	W232C	0.981
12:95895065:C:G	W232C	0.981
12:95898574:A:G	L176P	0.981

dbSNP variants (sampled 300 via entrez): RS1000005429 (12:95877887 C>A), RS1000022635 (12:95906749 A>C), RS1000034142 (12:95868257 C>T), RS1000086146 (12:95925480 C>T), RS1000098398 (12:95880733 G>A), RS1000106458 (12:95935308 A>T), RS1000156490 (12:95884828 C>A,T), RS1000161249 (12:95912577 T>A), RS1000181774 (12:95867471 C>T), RS1000182874 (12:95867720 C>G,T), RS1000291517 (12:95919444 A>T), RS1000299777 (12:95906183 G>A,T), RS1000426560 (12:95885156 G>A), RS1000428974 (12:95918486 T>C), RS1000520646 (12:95869126 A>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

8 associations (top):

Study	Trait	p-value
GCST001248_6	Pulmonary function	2.000000e-11
GCST001784_7	Pulmonary function (smoking interaction)	1.000000e-07
GCST002479_12	Lupus nephritis in systemic lupus erythematosus	2.000000e-06
GCST004185_54	Lung function (FEV1/FVC)	5.000000e-08
GCST007637_21	Diffusing capacity of carbon monoxide	2.000000e-06
GCST009240_270	Serum metabolite levels (CMS)	7.000000e-18
GCST009242_73	Serum metabolite levels	2.000000e-13
GCST010002_220	Refractive error	1.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0009369	diffusing capacity of the lung for carbon monoxide

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
pirinixic acid	affects binding, decreases expression, increases activity	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
Fonofos	increases methylation	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Parathion	increases methylation	1
Tretinoin	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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