CCDC85C

Summary

CCDC85C (coiled-coil domain containing 85C, HGNC:35459) is a protein-coding gene on chromosome 14q32.2, encoding Coiled-coil domain-containing protein 85C (A6NKD9). May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family.

Predicted to be involved in cerebral cortex development. Predicted to act upstream of or within several processes, including Notch signaling pathway; establishment of cell polarity; and radial glial cell differentiation. Located in adherens junction and nuclear speck.

Source: NCBI Gene 317762 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 149 total — 1 pathogenic
• MANE Select transcript: NM_001144995

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35459
Approved symbol	CCDC85C
Name	coiled-coil domain containing 85C
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205476
Ensembl biotype	protein_coding
OMIM	621283
Entrez	317762

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000380243, ENST00000554877, ENST00000554996, ENST00000555822, ENST00000556348, ENST00000557576, ENST00000557769

RefSeq mRNA: 1 — MANE Select: NM_001144995 NM_001144995

CCDS: CCDS45161

Canonical transcript exons

ENST00000380243 — 6 exons

Exon	Start	End
ENSE00001409188	99516188	99516286
ENSE00001484220	99500190	99515335
ENSE00001484231	99603167	99604207
ENSE00003540887	99536015	99536088
ENSE00003543194	99522133	99522240
ENSE00003588016	99517088	99517183

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 95.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8851 / max 99.0689, expressed in 1474 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144886	10.7690	1473
144884	0.0591	29
144885	0.0571	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.04	gold quality
cerebellar hemisphere	UBERON:0002245	94.98	gold quality
cerebellar cortex	UBERON:0002129	94.93	gold quality
buccal mucosa cell	CL:0002336	94.05	gold quality
cerebellum	UBERON:0002037	93.54	gold quality
esophagus squamous epithelium	UBERON:0006920	91.75	gold quality
apex of heart	UBERON:0002098	89.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.87	gold quality
gingival epithelium	UBERON:0001949	88.58	gold quality
caudate nucleus	UBERON:0001873	88.02	gold quality
esophagus mucosa	UBERON:0002469	87.88	gold quality
right adrenal gland	UBERON:0001233	87.77	gold quality
gingiva	UBERON:0001828	87.63	gold quality
anterior cingulate cortex	UBERON:0009835	87.42	gold quality
right adrenal gland cortex	UBERON:0035827	87.27	gold quality
cingulate cortex	UBERON:0003027	87.26	gold quality
left adrenal gland	UBERON:0001234	87.02	gold quality
left adrenal gland cortex	UBERON:0035825	86.85	gold quality
nucleus accumbens	UBERON:0001882	86.71	gold quality
transverse colon	UBERON:0001157	86.68	gold quality
putamen	UBERON:0001874	86.56	gold quality
esophagus	UBERON:0001043	86.55	gold quality
right frontal lobe	UBERON:0002810	86.37	gold quality
amygdala	UBERON:0001876	86.31	gold quality
mucosa of transverse colon	UBERON:0004991	86.20	gold quality
body of stomach	UBERON:0001161	86.09	gold quality
lower esophagus mucosa	UBERON:0035834	86.09	gold quality
adrenal cortex	UBERON:0001235	85.84	gold quality
heart left ventricle	UBERON:0002084	85.36	gold quality
lower esophagus	UBERON:0013473	85.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.89
E-MTAB-4850	no	6.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting CCDC85C, 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-4283	100.00	66.42	2097
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442

Literature-anchored findings (GeneRIF, showing 1)

• Genome-wide SNP analysis identified multiple suggestive novel loci and two of them were also significant in gene-based analysis (CCDC85C and NARS2) that survived after controlling for false-discovery rate at 0.05. (PMID:25649651)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc85ca	ENSDARG00000005232
danio_rerio	ccdc85cb	ENSDARG00000079555
mus_musculus	Ccdc85c	ENSMUSG00000084883
rattus_norvegicus	Ccdc85c	ENSRNOG00000065213
caenorhabditis_elegans		WBGENE00017931

Paralogs (2): CCDC85A (ENSG00000055813), CCDC85B (ENSG00000175602)

Protein

Protein identifiers

Coiled-coil domain-containing protein 85C — A6NKD9 (reviewed: A6NKD9)

All UniProt accessions (6): A6NKD9, G3V2D7, G3V4C8, G3V5D5, H0YJE0, H0YJY5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family. May play an important role in cortical development, especially in the maintenance of radial glia.

Subunit / interactions. May interact with ARVCF, CTNND1, CTNND2 and PKP4.

Subcellular location. Cell junction. Tight junction. Adherens junction.

Similarity. Belongs to the CCDC85 family.

RefSeq proteins (1): NP_001138467* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019359	CCDC85	Family

Pfam: PF10226

UniProt features (14 total): compositionally biased region 5, modified residue 3, region of interest 2, coiled-coil region 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKD9-F1	70.38	0.35

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): 2, 178, 246

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, MODULE_255, MODULE_317, GOBP_NEUROGENESIS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_CEREBRAL_CORTEX_DEVELOPMENT, GOBP_PALLIUM_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT, GOBP_GLIAL_CELL_DIFFERENTIATION, GOCC_CELL_CELL_JUNCTION, GOBP_TELENCEPHALON_DEVELOPMENT, chr14q32, SENESE_HDAC3_TARGETS_DN

GO Biological Process (6): Notch signaling pathway (GO:0007219), cell population proliferation (GO:0008283), cerebral cortex development (GO:0021987), establishment of cell polarity (GO:0030010), establishment of protein localization (GO:0045184), radial glial cell differentiation (GO:0060019)

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

GO Cellular Component (6): adherens junction (GO:0005912), bicellular tight junction (GO:0005923), nuclear speck (GO:0016607), cell junction (GO:0030054), apical junction complex (GO:0043296), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell junction	2
cell surface receptor signaling pathway	1
cellular process	1
pallium development	1
anatomical structure development	1
establishment or maintenance of cell polarity	1
establishment of localization	1
glial cell differentiation	1
binding	1
apical junction complex	1
tight junction	1
nuclear ribonucleoprotein granule	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC85C	ARHGAP23	Q9P227	605
CCDC85C	DTWD1	Q8N5C7	529
CCDC85C	ARHGAP21	Q5T5U3	506
CCDC85C	MPHOSPH10	O00566	476
CCDC85C	NIFK	Q9BYG3	460
CCDC85C	EBNA1BP2	Q99848	449
CCDC85C	SETD3	Q86TU7	447
CCDC85C	WWC1	Q8IX03	442
CCDC85C	MEAK7	Q6P9B6	421
CCDC85C	YAP1	P46937	418
CCDC85C	DHX35	Q9H5Z1	404
CCDC85C	PRR20A	P86496	400
CCDC85C	CCDC85A	Q96PX6	398
CCDC85C	AGFG2	O95081	397
CCDC85C	ZNF688	P0C7X2	371

IntAct

147 interactions, top by confidence:

A	B	Type	Score
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
GGPS1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CD4	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PSG9	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SCRN1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LDLRAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SKA3	CCDC85C	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.530

BioGRID (182): CCDC85C (Two-hybrid), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCDC85C (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

Diamond homologs: A2CEM9, A6NKD9, E9Q6B2, H2KYP0, Q0P485, Q0V989, Q15834, Q4V872, Q5SP85, Q6DHL7, Q6PDY0, Q96PX6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Activation of BAD and translocation to mitochondria	5	61.4×	3e-07
Activation of BH3-only proteins	7	56.1×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	54.2×	6e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	54.2×	6e-07
Intrinsic Pathway for Apoptosis	7	33.1×	6e-08
RHO GTPases activate PKNs	6	30.7×	8e-07
Loss of Nlp from mitotic centrosomes	10	25.6×	4e-10
Loss of proteins required for interphase microtubule organization from the centrosome	10	25.6×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	38.2×	6e-05
protein targeting	5	19.1×	1e-03
cilium assembly	11	8.4×	5e-05
intracellular protein localization	7	7.6×	4e-03
cell division	11	5.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	119
Likely benign	17
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
980622	GRCh37/hg19 14q32.2(chr14:99538014-100082239)x1	Pathogenic

SpliceAI

3175 predictions. Top by Δscore:

Variant	Effect	Δscore
14:99500760:TTTTA:T	acceptor_loss	1.0000
14:99500761:TTTAG:T	acceptor_loss	1.0000
14:99500763:TAG:T	acceptor_loss	1.0000
14:99500764:A:AT	acceptor_loss	1.0000
14:99502205:A:AG	acceptor_gain	1.0000
14:99502206:G:GT	acceptor_gain	1.0000
14:99502374:A:T	donor_gain	1.0000
14:99503609:A:AG	acceptor_gain	1.0000
14:99503610:G:GG	acceptor_gain	1.0000
14:99503642:CAG:C	donor_loss	1.0000
14:99503645:GT:G	donor_loss	1.0000
14:99503646:T:A	donor_loss	1.0000
14:99507070:TTGTA:T	acceptor_loss	1.0000
14:99507071:TGTAG:T	acceptor_loss	1.0000
14:99507072:GTAG:G	acceptor_loss	1.0000
14:99507073:TA:T	acceptor_loss	1.0000
14:99507074:A:AG	acceptor_gain	1.0000
14:99507074:AGAA:A	acceptor_loss	1.0000
14:99507075:G:A	acceptor_loss	1.0000
14:99507075:G:GA	acceptor_gain	1.0000
14:99507075:GA:G	acceptor_gain	1.0000
14:99507075:GAA:G	acceptor_gain	1.0000
14:99507075:GAAC:G	acceptor_gain	1.0000
14:99507075:GAACC:G	acceptor_gain	1.0000
14:99515332:CCAC:C	acceptor_gain	1.0000
14:99515333:CACC:C	acceptor_gain	1.0000
14:99515334:ACCT:A	acceptor_loss	1.0000
14:99515335:CCTGT:C	acceptor_loss	1.0000
14:99515336:C:A	acceptor_loss	1.0000
14:99515337:T:G	acceptor_loss	1.0000

AlphaMissense

2693 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:99515319:A:G	L396P	1.000
14:99515321:C:A	K395N	1.000
14:99515321:C:G	K395N	1.000
14:99515324:T:A	R394S	1.000
14:99515324:T:G	R394S	1.000
14:99515325:C:A	R394I	1.000
14:99515325:C:G	R394T	1.000
14:99515327:C:A	W393C	1.000
14:99515327:C:G	W393C	1.000
14:99515328:C:G	W393S	1.000
14:99515329:A:G	W393R	1.000
14:99515329:A:T	W393R	1.000
14:99515331:A:T	V392D	1.000
14:99516191:G:C	C389W	1.000
14:99516192:C:A	C389F	1.000
14:99516192:C:G	C389S	1.000
14:99516192:C:T	C389Y	1.000
14:99516193:A:G	C389R	1.000
14:99516193:A:T	C389S	1.000
14:99516194:C:A	M388I	1.000
14:99516194:C:G	M388I	1.000
14:99516194:C:T	M388I	1.000
14:99516195:A:C	M388R	1.000
14:99516195:A:G	M388T	1.000
14:99516195:A:T	M388K	1.000
14:99516201:C:G	R386P	1.000
14:99516204:A:T	V385D	1.000
14:99516207:A:C	I384S	1.000
14:99516207:A:T	I384N	1.000
14:99516211:C:G	A383P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002771 (14:99508730 G>C), RS1000006783 (14:99536100 C>A,G,T), RS1000007808 (14:99560733 C>G), RS1000051674 (14:99508549 A>G), RS1000101774 (14:99571189 C>T), RS1000116326 (14:99540891 C>G,T), RS1000130863 (14:99597845 C>T), RS1000137056 (14:99580473 A>C,G), RS1000163775 (14:99580823 C>T), RS1000175936 (14:99563289 C>A,T), RS1000222151 (14:99583793 G>A), RS1000285563 (14:99575097 G>A), RS1000318344 (14:99504745 C>T), RS1000352896 (14:99533997 G>A), RS1000363355 (14:99580651 C>T)

Disease associations

OMIM: gene MIM:621283 | disease phenotypes: MIM:618147

GenCC curated gene-disease

Mondo (1): intellectual developmental disorder with hypertelorism and distinctive facies (MONDO:0029143)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002775_3	Alzheimer’s disease (survival time)	2.000000e-06
GCST003474_8	Scalp hair shape	1.000000e-07
GCST004744_30	Lung adenocarcinoma	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Cadmium Chloride	decreases reaction, increases localization, affects binding, increases reaction, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
manganese chloride	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetylcysteine	decreases reaction, increases localization	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Plant Extracts	decreases expression, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, affects cotreatment	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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