CCDC138

Summary

CCDC138 (coiled-coil domain containing 138, HGNC:26531) is a protein-coding gene on chromosome 2q13, encoding Coiled-coil domain-containing protein 138 (Q96M89).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 151 total — 2 pathogenic, 4 likely-pathogenic
• MANE Select transcript: NM_144978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26531
Approved symbol	CCDC138
Name	coiled-coil domain containing 138
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32745
Ensembl gene	ENSG00000163006
Ensembl biotype	protein_coding
Entrez	165055

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000295124, ENST00000409529, ENST00000412964, ENST00000447782, ENST00000456512, ENST00000470608, ENST00000608781, ENST00000609740, ENST00000870672, ENST00000870673, ENST00000870674, ENST00000870675, ENST00000925777, ENST00000925778, ENST00000925779, ENST00000925780, ENST00000925781, ENST00000925782, ENST00000925783, ENST00000925784, ENST00000925785, ENST00000958376

RefSeq mRNA: 15 — MANE Select: NM_144978 NM_001303105, NM_001303106, NM_001351544, NM_001351545, NM_001351548, NM_001351549, NM_001351551, NM_001351553, NM_001351554, NM_001351555, NM_001351557, NM_001351559, NM_001351561, NM_001351565, NM_144978

CCDS: CCDS2080, CCDS77447

Canonical transcript exons

ENST00000295124 — 15 exons

Exon	Start	End
ENSE00001070580	108873451	108873589
ENSE00001129264	108786771	108786915
ENSE00001330218	108791675	108791802
ENSE00003492507	108812820	108812927
ENSE00003515085	108846738	108846930
ENSE00003530868	108876088	108876578
ENSE00003571732	108798428	108798586
ENSE00003580273	108815941	108816105
ENSE00003595343	108856794	108856970
ENSE00003595908	108839185	108839301
ENSE00003603031	108788032	108788089
ENSE00003653512	108788852	108788966
ENSE00003661113	108812631	108812708
ENSE00003690591	108794540	108794721
ENSE00003692204	108804889	108805008

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 91.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2256 / max 279.7789, expressed in 1498 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21918	9.2256	1498

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.75	gold quality
sperm	CL:0000019	90.61	gold quality
ventricular zone	UBERON:0003053	85.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.95	gold quality
ganglionic eminence	UBERON:0004023	82.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.32	gold quality
secondary oocyte	CL:0000655	81.77	gold quality
right uterine tube	UBERON:0001302	80.41	gold quality
cortical plate	UBERON:0005343	79.14	gold quality
calcaneal tendon	UBERON:0003701	78.55	gold quality
testis	UBERON:0000473	77.17	gold quality
bronchial epithelial cell	CL:0002328	77.12	gold quality
right testis	UBERON:0004534	76.04	gold quality
left testis	UBERON:0004533	76.02	gold quality
endothelial cell	CL:0000115	75.51	gold quality
bronchus	UBERON:0002185	75.47	gold quality
oviduct epithelium	UBERON:0004804	75.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.32	silver quality
adrenal tissue	UBERON:0018303	74.52	gold quality
cerebellar hemisphere	UBERON:0002245	73.76	gold quality
cerebellar cortex	UBERON:0002129	73.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.47	gold quality
stromal cell of endometrium	CL:0002255	72.39	gold quality
islet of Langerhans	UBERON:0000006	72.11	gold quality
cerebellum	UBERON:0002037	71.92	gold quality
rectum	UBERON:0001052	71.71	gold quality
fallopian tube	UBERON:0003889	70.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.45	gold quality
vermiform appendix	UBERON:0001154	70.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting CCDC138, 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-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-643	97.35	67.91	805

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc138	ENSMUSG00000038010
rattus_norvegicus	Ccdc138	ENSRNOG00000028581

Protein

Protein identifiers

Coiled-coil domain-containing protein 138 — Q96M89 (reviewed: Q96M89)

All UniProt accessions (5): Q96M89, F8WF51, H7BZ08, H7C005, V9GZ19

Isoforms (2)

UniProt ID	Names	Canonical?
Q96M89-1	1	yes
Q96M89-2	2

RefSeq proteins (15): NP_001290034, NP_001290035, NP_001338473, NP_001338474, NP_001338477, NP_001338478, NP_001338480, NP_001338482, NP_001338483, NP_001338484, NP_001338486, NP_001338488, NP_001338490, NP_001338494, NP_659415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038798	CCDC138	Family
IPR048750	CCDC138_C	Domain
IPR048751	CCDC138_CC	Domain

Pfam: PF21035, PF21037

UniProt features (9 total): modified residue 3, splice variant 2, sequence variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96M89-F1	73.25	0.52

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 (3): 48, 49, 469

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): CAGCTG_AP4_Q5, WEI_MYCN_TARGETS_WITH_E_BOX, TGACATY_UNKNOWN, ATCATGA_MIR433, GATA4_Q3, NUYTTEN_EZH2_TARGETS_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, JOHNSTONE_PARVB_TARGETS_3_DN, NFE2L2.V2, HMGA1_TARGET_GENES, NCOA6_TARGET_GENES, PCGF1_TARGET_GENES, RBM34_TARGET_GENES, SNRNP70_TARGET_GENES, TASOR_TARGET_GENES

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

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC138	TBC1D31	Q96DN5	602
CCDC138	CCDC61	Q9Y6R9	591
CCDC138	PIBF1	Q8WXW3	590
CCDC138	TTLL5	Q6EMB2	572
CCDC138	TTLL10	Q6ZVT0	566
CCDC138	CCDC22	O60826	559
CCDC138	CCDC186	Q7Z3E2	526
CCDC138	CEP20	Q96NB1	523
CCDC138	VPS50	Q96JG6	518
CCDC138	RABL6	Q3YEC7	489
CCDC138	ANKRD55	Q3KP44	477
CCDC138	VPS54	Q9P1Q0	466
CCDC138	VPS33A	Q96AX1	458
CCDC138	VPS51	Q9UID3	458
CCDC138	VPS33B	Q9H267	456

IntAct

83 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
FAM9B	GEMIN2	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
CEP162	CCP110	psi-mi:“MI:2364”(proximity)	0.420
AHI1	OFD1	psi-mi:“MI:2364”(proximity)	0.420
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
CCDC138	HYOU1	psi-mi:“MI:0915”(physical association)	0.400
UBAC1	CCDC138	psi-mi:“MI:0915”(physical association)	0.370
CEP290	SUPT5H	psi-mi:“MI:0914”(association)	0.350
PCM1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CEP162	IPO5	psi-mi:“MI:0914”(association)	0.350
SSX2IP	IPO7	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
SPZ1	OFD1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350

BioGRID (162): CCDC138 (Affinity Capture-MS), CCDC138 (Affinity Capture-MS), CCDC138 (Proximity Label-MS), CCDC138 (Proximity Label-MS), CCDC138 (Proximity Label-MS), CCDC138 (Proximity Label-MS), CCDC138 (Proximity Label-MS), CCDC138 (Affinity Capture-MS), CCDC138 (Affinity Capture-MS), CCDC138 (Affinity Capture-MS), CCDC138 (Affinity Capture-MS), CCDC138 (Affinity Capture-MS), CCDC138 (Proximity Label-MS), CCDC138 (Proximity Label-MS), CCDC138 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4I9Y1, A0A0R4IBK5, A2ARZ3, A5WUT8, A6NKT7, A7S7F2, E9Q3L2, E9Q555, F1QB81, F5H4B4, H2QII6, O08662, O14715, O15050, O43310, P0DJD0, P0DJD1, P13864, P42356, P49792, Q06190, Q0V9S3, Q0VF22, Q16533, Q1LVQ2, Q24K09, Q2T9I9, Q4R6W9, Q4V847, Q5U228, Q63HN8, Q65Z40, Q6NU22, Q6NU51, Q7TPV2, Q7Z3J3, Q80TA9, Q811D2, Q86Y13, Q921I6

Diamond homologs: Q0VF22, Q95JJ5, Q96M89

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Anchoring of the basal body to the plasma membrane	19	31.6×	2e-21
Loss of Nlp from mitotic centrosomes	13	30.3×	3e-14
Loss of proteins required for interphase microtubule organization from the centrosome	13	30.3×	3e-14
AURKA Activation by TPX2	13	29.1×	4e-14
Recruitment of mitotic centrosome proteins and complexes	13	26.0×	1e-13
Regulation of PLK1 Activity at G2/M Transition	13	24.3×	3e-13
Recruitment of NuMA to mitotic centrosomes	13	22.3×	8e-13
Cilium Assembly	9	14.4×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	57.0×	1e-08
non-motile cilium assembly	7	22.6×	5e-06
cilium assembly	13	10.6×	7e-08
intracellular protein localization	7	8.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	121
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1526886	GRCh37/hg19 2q12.3-13(chr2:108446955-110504318)	Pathogenic
57544	GRCh38/hg38 2q12.3-13(chr2:108579001-109736559)x1	Pathogenic
1340973	GRCh37/hg19 2q12.2-12.3(chr2:107020782-110068385)x1	Likely pathogenic
562663	GRCh37/hg19 2q12.2-13(chr2:107020782-111365996)x1	Likely pathogenic
625546	GRCh37/hg19 2q12.3-13(chr2:109301074-110482930)	Likely pathogenic
814292	GRCh37/hg19 2q12.3-13(chr2:108499809-110504318)x1	Likely pathogenic

SpliceAI

2680 predictions. Top by Δscore:

Variant	Effect	Δscore
2:108788030:A:AG	acceptor_gain	1.0000
2:108788030:AGTAT:A	acceptor_gain	1.0000
2:108788031:G:GG	acceptor_gain	1.0000
2:108788031:GT:G	acceptor_gain	1.0000
2:108788031:GTAT:G	acceptor_gain	1.0000
2:108788031:GTATG:G	acceptor_gain	1.0000
2:108788949:GCAC:G	donor_gain	1.0000
2:108791754:G:GG	donor_gain	1.0000
2:108794536:GCA:G	acceptor_loss	1.0000
2:108794537:CA:C	acceptor_loss	1.0000
2:108794538:A:AG	acceptor_gain	1.0000
2:108794538:AG:A	acceptor_loss	1.0000
2:108794538:AGTT:A	acceptor_gain	1.0000
2:108794539:G:GT	acceptor_gain	1.0000
2:108794539:GT:G	acceptor_gain	1.0000
2:108794539:GTT:G	acceptor_gain	1.0000
2:108794539:GTTG:G	acceptor_gain	1.0000
2:108794539:GTTGC:G	acceptor_gain	1.0000
2:108794718:GCAG:G	donor_gain	1.0000
2:108794720:AGG:A	donor_loss	1.0000
2:108794721:GGT:G	donor_loss	1.0000
2:108794722:GTA:G	donor_loss	1.0000
2:108794723:T:G	donor_loss	1.0000
2:108798426:A:AG	acceptor_gain	1.0000
2:108798427:G:GG	acceptor_gain	1.0000
2:108798427:GT:G	acceptor_gain	1.0000
2:108798427:GTGT:G	acceptor_gain	1.0000
2:108804883:TCCTA:T	acceptor_loss	1.0000
2:108804884:CCTAG:C	acceptor_loss	1.0000
2:108804885:CTAGC:C	acceptor_loss	1.0000

AlphaMissense

4409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:108873558:A:C	S601R	0.999
2:108873560:T:A	S601R	0.999
2:108873560:T:G	S601R	0.999
2:108876170:T:C	F639L	0.999
2:108876172:T:A	F639L	0.999
2:108876172:T:G	F639L	0.999
2:108876186:T:C	L644P	0.998
2:108873577:T:C	L607P	0.997
2:108876171:T:G	F639C	0.997
2:108876132:T:C	L626P	0.996
2:108876171:T:C	F639S	0.996
2:108873580:C:T	S608F	0.995
2:108876184:T:A	N643K	0.995
2:108876184:T:G	N643K	0.995
2:108812691:C:A	R306S	0.994
2:108812692:G:C	R306P	0.994
2:108873556:T:C	L600P	0.994
2:108876191:T:C	S646P	0.994
2:108876207:T:C	L651P	0.994
2:108846910:T:A	V499D	0.993
2:108873579:T:C	S608P	0.993
2:108873580:C:A	S608Y	0.993
2:108846764:G:C	R450S	0.992
2:108846764:G:T	R450S	0.992
2:108856824:T:C	L516P	0.992
2:108876104:T:C	F617L	0.992
2:108876106:T:A	F617L	0.992
2:108876106:T:G	F617L	0.992
2:108876148:G:C	R631S	0.992
2:108876148:G:T	R631S	0.992

dbSNP variants (sampled 300 via entrez): RS1000014844 (2:108840757 T>C,G), RS1000028371 (2:108833257 A>T), RS1000029304 (2:108815569 G>A), RS1000059657 (2:108840998 T>A,C), RS1000083705 (2:108805789 T>C), RS1000089282 (2:108790555 A>G), RS1000142442 (2:108805368 A>G), RS1000180889 (2:108804830 T>C), RS1000201814 (2:108853178 C>A,T), RS1000271486 (2:108790739 A>G,T), RS1000282764 (2:108834476 A>G), RS1000289746 (2:108847001 T>G), RS1000358597 (2:108860496 A>G), RS1000427737 (2:108818128 A>G), RS1000469509 (2:108797411 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:608033, MIM:129490, MIM:158580, MIM:617143, MIM:224900

GenCC curated gene-disease

Mondo (6): familial acute necrotizing encephalopathy (MONDO:0011953), ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (MONDO:0007509), autosomal recessive hypohidrotic ectodermal dysplasia (MONDO:0016619), neuronopathy, distal hereditary motor, type 7A (MONDO:0008024), congenital myasthenic syndrome 20 (MONDO:0014939), ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (MONDO:0009147)

Orphanet (5): Familial acute necrotizing encephalopathy (Orphanet:88619), Autosomal dominant hypohidrotic ectodermal dysplasia (Orphanet:1810), Hypohidrotic ectodermal dysplasia (Orphanet:238468), Autosomal recessive hypohidrotic ectodermal dysplasia (Orphanet:248), Distal hereditary motor neuropathy type 7 (Orphanet:139589)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003474_7	Scalp hair shape	3.000000e-119
GCST003475_4	Beard thickness	1.000000e-15
GCST003477_5	Monobrow thickness	1.000000e-07

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D053360	Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive	C16.131.077.350.348; C16.131.831.350.348; C16.320.850.250.348; C17.800.804.350.348; C17.800.827.250.348
C563562	Neuropathy, Distal Hereditary Motor, Type VIIA (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
Quercetin	increases phosphorylation, decreases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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