CCDC136

Summary

CCDC136 (coiled-coil domain containing 136, HGNC:22225) is a protein-coding gene on chromosome 7q32.1, encoding Coiled-coil domain-containing protein 136 (Q96JN2). May play a role in acrosome formation in spermatogenesis and in fertilization.

Predicted to be involved in acrosome assembly and single fertilization. Predicted to be located in cytoplasmic vesicle and membrane. Predicted to be active in acrosomal membrane.

Source: NCBI Gene 64753 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 188 total
• MANE Select transcript: NM_022742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22225
Approved symbol	CCDC136
Name	coiled-coil domain containing 136
Location	7q32.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1793, NAG6, DKFZP434G156
Ensembl gene	ENSG00000128596
Ensembl biotype	protein_coding
OMIM	611902
Entrez	64753

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 27 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297788, ENST00000378685, ENST00000459946, ENST00000460941, ENST00000464672, ENST00000464832, ENST00000471729, ENST00000472049, ENST00000480137, ENST00000485832, ENST00000485998, ENST00000487361, ENST00000488925, ENST00000494552, ENST00000528772, ENST00000864234, ENST00000864235, ENST00000864236, ENST00000864237, ENST00000864238, ENST00000864239, ENST00000864240, ENST00000864241, ENST00000864242, ENST00000864243, ENST00000864244, ENST00000961325, ENST00000961326, ENST00000961327, ENST00000961328, ENST00000961329, ENST00000961330

RefSeq mRNA: 10 — MANE Select: NM_022742 NM_001201372, NM_001363423, NM_001363424, NM_001367761, NM_001367762, NM_001367763, NM_001367764, NM_001367765, NM_001367766, NM_022742

CCDS: CCDS47704, CCDS56510, CCDS94193

Canonical transcript exons

ENST00000297788 — 18 exons

Exon	Start	End
ENSE00001602312	128817758	128817864
ENSE00001627946	128806237	128806395
ENSE00001656401	128794348	128794602
ENSE00001673031	128791968	128792427
ENSE00001689246	128806688	128806858
ENSE00001717682	128794694	128794768
ENSE00001822854	128821799	128822130
ENSE00003473736	128809450	128809644
ENSE00003483496	128814638	128814919
ENSE00003532909	128815614	128815931
ENSE00003570634	128804650	128804761
ENSE00003593677	128810139	128810366
ENSE00003600146	128805761	128805901
ENSE00003625111	128805359	128805524
ENSE00003644533	128811800	128812312
ENSE00003666102	128801186	128801509
ENSE00003669838	128812708	128812929
ENSE00003673236	128807360	128807545

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6800 / max 314.6359, expressed in 1372 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80965	10.0568	1370
80966	0.3306	132
80964	0.2594	119
204686	0.0333	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.12	gold quality
left testis	UBERON:0004533	99.06	gold quality
right testis	UBERON:0004534	98.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.97	gold quality
cerebellar hemisphere	UBERON:0002245	97.95	gold quality
cerebellar cortex	UBERON:0002129	97.93	gold quality
cerebellum	UBERON:0002037	97.50	gold quality
testis	UBERON:0000473	96.62	gold quality
right frontal lobe	UBERON:0002810	96.07	gold quality
cortical plate	UBERON:0005343	95.91	gold quality
prefrontal cortex	UBERON:0000451	95.76	gold quality
cerebellar vermis	UBERON:0004720	95.45	gold quality
hypothalamus	UBERON:0001898	95.13	gold quality
primary visual cortex	UBERON:0002436	94.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.83	gold quality
anterior cingulate cortex	UBERON:0009835	94.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.40	gold quality
frontal cortex	UBERON:0001870	94.22	gold quality
neocortex	UBERON:0001950	94.22	gold quality
occipital lobe	UBERON:0002021	94.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.54	gold quality
cerebral cortex	UBERON:0000956	92.41	gold quality
spinal cord	UBERON:0002240	92.31	gold quality
middle temporal gyrus	UBERON:0002771	92.02	gold quality
amygdala	UBERON:0001876	91.60	gold quality
brain	UBERON:0000955	91.43	gold quality
ganglionic eminence	UBERON:0004023	91.40	gold quality
substantia nigra	UBERON:0002038	91.19	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1131.08
E-MTAB-7316	yes	42.17
E-GEOD-134144	yes	28.80
E-GEOD-84465	yes	6.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting CCDC136, 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-6825-5P	99.96	69.81	3431
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-6857-3P	96.70	65.43	915

Literature-anchored findings (GeneRIF, showing 3)

• Data suggest that NAG6 may represent a candidate tumor suppressor gene at 7q31-32 loci associated with gastric carcinoma. (PMID:15112360)
• CCDC136 locus showed association with a comparable reading/language measure. (PMID:25065397)
• Missense variant in CCDC136 gene is associated with reading disability. (PMID:28866788)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc136b	ENSDARG00000057921
danio_rerio	ccdc136a	ENSDARG00000075513
mus_musculus	Ccdc136	ENSMUSG00000029769
rattus_norvegicus	Ccdc136	ENSRNOG00000007100
drosophila_melanogaster	Slmap	FBGN0040011
caenorhabditis_elegans		WBGENE00019766

Paralogs (2): TRAF3IP3 (ENSG00000009790), SLMAP (ENSG00000163681)

Protein

Protein identifiers

Coiled-coil domain-containing protein 136 — Q96JN2 (reviewed: Q96JN2)

Alternative names: Nasopharyngeal carcinoma-associated gene 6 protein

All UniProt accessions (8): Q96JN2, C9IYI5, C9J884, C9JAD8, C9JE17, C9JU31, H0Y876, H7C4R2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in acrosome formation in spermatogenesis and in fertilization.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane.

Tissue specificity. Expressed in gastric tissues. Down-regulated in gastric cancer.

Miscellaneous. Restriction fragment length polymorphisms (RFLPs) in gastric cancer showed loss of 5 kb fragment in comparison with the corresponding normal tissue.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96JN2-1	1	yes
Q96JN2-2	2
Q96JN2-3	3
Q96JN2-4	4

RefSeq proteins (10): NP_001188301, NP_001350352, NP_001350353, NP_001354690, NP_001354691, NP_001354692, NP_001354693, NP_001354694, NP_001354695, NP_073579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051176	Cent_Immune-Sig_Mod	Family

UniProt features (20 total): splice variant 6, compositionally biased region 3, sequence variant 2, sequence conflict 2, region of interest 2, coiled-coil region 2, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JN2-F1	69.24	0.25

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: 99 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, AP2_Q3, GOBP_MALE_GAMETE_GENERATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, chr7q32, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, PU1_Q6, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_FERTILIZATION

GO Biological Process (4): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283), single fertilization (GO:0007338), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (3): acrosomal membrane (GO:0002080), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
male gamete generation	1
fertilization	1
cellular developmental process	1
acrosomal vesicle	1
secretory granule membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1493 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC136	MEGF10	Q96KG7	825
CCDC136	TMEM8B	A6NDV4	671
CCDC136	MEGF11	A6BM72	609
CCDC136	MEGF6	O75095	588
CCDC136	ZNF385D	Q9H6B1	577
CCDC136	FAM90A7	A6NKC0	570
CCDC136	BRD7	Q9NPI1	536
CCDC136	TSPAN4	O14817	507
CCDC136	KIAA0319	Q5VV43	506
CCDC136	DNAAF4	Q8WXU2	506
CCDC136	AP2M1	P20172	468
CCDC136	RBFOX2	O43251	438
CCDC136	SPEM3	A0A1B0GUW6	432
CCDC136	SPATA31F1	Q6ZU69	432
CCDC136	DCDC2	Q9UHG0	427

IntAct

41 interactions, top by confidence:

A	B	Type	Score
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
ASB7	POLR3A	psi-mi:“MI:0914”(association)	0.530
COG5	BSG	psi-mi:“MI:0914”(association)	0.530
ATG14	CETN2	psi-mi:“MI:0914”(association)	0.530
CCDC136	ZNF581	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	ZNF490	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	LENG1	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	NEBL	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	PDLIM5	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	FAM107A	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	PSMD9	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	TXLNA	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	CCHCR1	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	MBD1	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	SMARCA2	psi-mi:“MI:0915”(physical association)	0.370
CCDC136	WT1	psi-mi:“MI:0915”(physical association)	0.370
PKN2	CCDC136	psi-mi:“MI:0915”(physical association)	0.370
STK11	H2AX	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CFAP184	TARS3	psi-mi:“MI:0914”(association)	0.350
PDE3A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ANGPT4	POTEF	psi-mi:“MI:0914”(association)	0.350
CCDC136	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SYCE1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
SYNC	NDC80	psi-mi:“MI:0914”(association)	0.350

BioGRID (226): CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid), CCDC136 (Two-hybrid)

ESM2 similar proteins: A0A1W2P884, A2AM05, A2AUM9, A3KNA5, A6PWD2, A9QT41, B1AJZ9, B8JK76, B9V5F5, E9Q1U1, O35550, O88522, P0CB05, Q05D60, Q0KK56, Q3TVA9, Q3UPP8, Q4L180, Q4R703, Q5R829, Q5SZL2, Q5U3Z6, Q6DD09, Q6P132, Q6P2H3, Q6P6L0, Q6TMG5, Q70FJ1, Q7M6Y5, Q7Z7B0, Q86SQ7, Q8BMK0, Q8BVC4, Q8K3K8, Q8K4T4, Q8R5M4, Q8TBY8, Q90Z16, Q95JK1, Q95KU9

Diamond homologs: Q14BN4, Q3TVA9, Q3URD3, Q96JN2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	156
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3312 predictions. Top by Δscore:

Variant	Effect	Δscore
7:128792423:GGAGG:G	donor_gain	1.0000
7:128792424:GAGG:G	donor_gain	1.0000
7:128792424:GAGGG:G	donor_gain	1.0000
7:128792425:AGGGT:A	donor_loss	1.0000
7:128792426:GG:G	donor_gain	1.0000
7:128792426:GGGT:G	donor_loss	1.0000
7:128792427:GG:G	donor_gain	1.0000
7:128792427:GGTG:G	donor_loss	1.0000
7:128792428:GTG:G	donor_loss	1.0000
7:128792429:T:A	donor_loss	1.0000
7:128794347:GGGGA:G	acceptor_gain	1.0000
7:128794599:CAGGG:C	donor_loss	1.0000
7:128794601:GG:G	donor_gain	1.0000
7:128794602:GG:G	donor_gain	1.0000
7:128794603:G:GG	donor_gain	1.0000
7:128794688:CTGCA:C	acceptor_loss	1.0000
7:128794690:GCA:G	acceptor_loss	1.0000
7:128794691:CA:C	acceptor_loss	1.0000
7:128794692:A:AG	acceptor_gain	1.0000
7:128794692:A:C	acceptor_loss	1.0000
7:128794692:AG:A	acceptor_gain	1.0000
7:128794692:AGG:A	acceptor_gain	1.0000
7:128794693:G:GC	acceptor_loss	1.0000
7:128794693:G:GT	acceptor_gain	1.0000
7:128794693:GG:G	acceptor_gain	1.0000
7:128794693:GGG:G	acceptor_gain	1.0000
7:128794764:CCAAG:C	donor_loss	1.0000
7:128794767:AGG:A	donor_loss	1.0000
7:128794768:GGT:G	donor_loss	1.0000
7:128794769:G:C	donor_loss	1.0000

AlphaMissense

7712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:128794513:T:C	L61P	0.999
7:128794534:T:C	L68P	0.999
7:128794546:T:C	L72P	0.999
7:128794597:T:C	L89P	0.999
7:128794697:T:C	L92P	0.999
7:128794700:T:C	L93P	0.999
7:128794558:G:C	R76P	0.998
7:128794712:G:C	R97P	0.998
7:128794732:G:C	A104P	0.998
7:128794763:T:C	L114P	0.998
7:128801192:T:C	L118P	0.998
7:128794723:G:C	A101P	0.997
7:128794741:T:C	F107L	0.997
7:128794743:C:A	F107L	0.997
7:128794743:C:G	F107L	0.997
7:128801435:T:C	L199P	0.997
7:128794715:T:C	L98P	0.996
7:128801201:T:C	L121P	0.996
7:128804707:T:C	L243P	0.996
7:128805846:T:C	L345P	0.996
7:128794564:T:C	L78P	0.995
7:128794587:T:C	S86P	0.995
7:128794754:T:C	I111T	0.995
7:128804740:T:C	L254P	0.995
7:128794504:T:C	L58P	0.994
7:128794516:G:C	R62P	0.994
7:128804728:T:C	L250P	0.994
7:128805834:T:C	L341P	0.994
7:128817830:T:A	W1146R	0.994
7:128817830:T:C	W1146R	0.994

dbSNP variants (sampled 300 via entrez): RS1000023248 (7:128788975 G>A), RS1000054363 (7:128789266 G>A), RS1000369486 (7:128795155 G>A,C), RS1000440963 (7:128821812 T>A), RS1000443412 (7:128814426 G>A), RS1000512189 (7:128807230 T>C), RS1000586971 (7:128793610 T>C), RS1000771702 (7:128816048 C>A,G,T), RS1000792276 (7:128821330 C>G), RS1000825418 (7:128816295 T>G), RS1000884961 (7:128797992 A>C), RS1000905171 (7:128819742 C>G), RS1000920956 (7:128820046 A>T), RS1001157145 (7:128818166 C>T), RS1001185980 (7:128794938 C>T)

Disease associations

OMIM: gene MIM:611902 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004401_3	Reading disability or specific language impairment (pleiotropy)	4.000000e-07
GCST004402_3	Reading disability or specific language impairment adjusted for intelligence quotient (pleiotropy)	3.000000e-07
GCST010796_1430	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_1431	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1432	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-11
GCST010796_1433	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_1434	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST011205_15	Hypertrophic cardiomyopathy (MTAG)	2.000000e-09
GCST011211_10	Hypertrophic cardiomyopathy	9.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	7
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cisplatin	affects expression	1

Clinical trials (associated diseases)

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