CCDC32

Summary

CCDC32 (coiled-coil domain containing 32, HGNC:28295) is a protein-coding gene on chromosome 15q15.1, encoding Coiled-coil domain-containing protein 32 (Q9BV29). Regulates clathrin-mediated endocytsois of cargos such as transferrin probably through the association and modulation of adaptor protein complex 2 (AP-2).

Involved in head development and regulation of clathrin-dependent endocytosis. Part of clathrin-coated pit.

Source: NCBI Gene 90416 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiofacioneurodevelopmental syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 20 total — 4 pathogenic
• Phenotypes (HPO): 25
• MANE Select transcript: NM_001080792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28295
Approved symbol	CCDC32
Name	coiled-coil domain containing 32
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC20481
Ensembl gene	ENSG00000128891
Ensembl biotype	protein_coding
OMIM	618941
Entrez	90416

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000358005, ENST00000416810, ENST00000558113, ENST00000558750, ENST00000558871, ENST00000558918, ENST00000559103, ENST00000559153, ENST00000559291, ENST00000559911, ENST00000560109, ENST00000560305, ENST00000560535, ENST00000561011, ENST00000698443, ENST00000903471, ENST00000903472, ENST00000963707, ENST00000963708

RefSeq mRNA: 13 — MANE Select: NM_001080792 NM_001080791, NM_001080792, NM_001289132, NM_001382434, NM_001382435, NM_001382436, NM_001382437, NM_001382438, NM_001382439, NM_001382440, NM_001382441, NM_001382442, NM_052849

CCDS: CCDS10060, CCDS73706

Canonical transcript exons

ENST00000416810 — 4 exons

Exon	Start	End
ENSE00001933860	40553099	40554127
ENSE00002572819	40564976	40565042
ENSE00003500940	40557216	40557372
ENSE00003556820	40562772	40563027

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 93.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.3250 / max 178.9283, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149497	23.1464	1817
149498	0.1786	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	93.14	gold quality
monocyte	CL:0000576	91.82	gold quality
leukocyte	CL:0000738	91.65	gold quality
bone marrow cell	CL:0002092	90.35	gold quality
ileal mucosa	UBERON:0000331	89.31	gold quality
pancreas	UBERON:0001264	89.04	gold quality
apex of heart	UBERON:0002098	89.01	gold quality
rectum	UBERON:0001052	88.70	gold quality
right adrenal gland cortex	UBERON:0035827	88.37	gold quality
right adrenal gland	UBERON:0001233	88.29	gold quality
cortical plate	UBERON:0005343	88.25	gold quality
lymph node	UBERON:0000029	88.22	gold quality
colonic epithelium	UBERON:0000397	88.10	gold quality
gall bladder	UBERON:0002110	88.08	gold quality
descending thoracic aorta	UBERON:0002345	87.88	gold quality
vermiform appendix	UBERON:0001154	87.71	gold quality
body of pancreas	UBERON:0001150	87.52	gold quality
left adrenal gland	UBERON:0001234	87.48	gold quality
granulocyte	CL:0000094	87.27	gold quality
gastrocnemius	UBERON:0001388	87.16	gold quality
adrenal gland	UBERON:0002369	87.09	gold quality
mucosa of transverse colon	UBERON:0004991	87.05	gold quality
spleen	UBERON:0002106	86.99	gold quality
left adrenal gland cortex	UBERON:0035825	86.97	gold quality
thoracic aorta	UBERON:0001515	86.94	gold quality
left ovary	UBERON:0002119	86.93	gold quality
ascending aorta	UBERON:0001496	86.92	gold quality
smooth muscle tissue	UBERON:0001135	86.87	gold quality
right atrium auricular region	UBERON:0006631	86.84	gold quality
adrenal tissue	UBERON:0018303	86.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting CCDC32, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-640	98.44	66.93	644

Literature-anchored findings (GeneRIF, showing 1)

• Loss of function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. (PMID:32307552)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc32	ENSDARG00000073962
mus_musculus	Ccdc32	ENSMUSG00000039983
rattus_norvegicus	Ccdc32	ENSRNOG00000010472

Protein

Protein identifiers

Coiled-coil domain-containing protein 32 — Q9BV29 (reviewed: Q9BV29)

All UniProt accessions (7): Q9BV29, A0A8V8TLS2, H0YLI5, H0YLN5, H0YM19, H0YMC0, H0YN78

UniProt curated annotations — full annotation on UniProt →

Function. Regulates clathrin-mediated endocytsois of cargos such as transferrin probably through the association and modulation of adaptor protein complex 2 (AP-2). Has a role in ciliogenesis. Required for proper cephalic and left/right axis development.

Subunit / interactions. Interacts with AP2S1; the interaction is direct and mediates association with adaptor protein complex 2 (AP-2).

Subcellular location. Membrane. Coated pit.

Disease relevance. Cardiofacioneurodevelopmental syndrome (CFNDS) [MIM:619123] An autosomal recessive disorder characterized by global developmental delay, feeding difficulties, microcephaly and dysmorphic features. Additional features include cleft lip, cleft palate, variable cardiac defects, and abdominal situs inversus with asplenia. Brain imaging reveals cerebellar hypoplasia. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BV29-1	1	yes
Q9BV29-2	2
Q9BV29-3	3

RefSeq proteins (13): NP_001074260, NP_001074261, NP_001276061, NP_001369363, NP_001369364, NP_001369365, NP_001369366, NP_001369367, NP_001369368, NP_001369369, NP_001369370, NP_001369371, NP_443081 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028039	CCDC32	Family

Pfam: PF14989

UniProt features (7 total): splice variant 3, chain 1, region of interest 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV29-F1	69.74	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GOBP_VESICLE_MEDIATED_TRANSPORT, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, CADWELL_ATG16L1_TARGETS_DN, GOBP_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_CILIUM_ORGANIZATION, TGTGTGA_MIR377, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_REGULATION_OF_ENDOCYTOSIS, GOBP_HEAD_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_TRANSPORT, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (4): cilium organization (GO:0044782), head development (GO:0060322), regulation of clathrin-dependent endocytosis (GO:2000369), cell projection organization (GO:0030030)

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

GO Cellular Component (2): clathrin-coated pit (GO:0005905), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	1
plasma membrane bounded cell projection organization	1
anatomical structure development	1
regulation of receptor-mediated endocytosis	1
clathrin-dependent endocytosis	1
cellular component organization	1
binding	1
endomembrane system	1
membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC32	CBX3	Q13185	701
CCDC32	F8VZ95	F8VZ95	582
CCDC32	WIPF2	Q8TF74	506
CCDC32	BCAS3	Q9H6U6	449
CCDC32	ARL10	Q8N8L6	447
CCDC32	SNX27	Q96L92	437
CCDC32	OR5T1	Q8NG75	431
CCDC32	PTPRN2	Q92932	428
CCDC32	FAM228A	Q86W67	419
CCDC32	ZC2HC1C	Q53FD0	397
CCDC32	CPSF4L	A6NMK7	391
CCDC32	RAD51C	O43502	387
CCDC32	HIGD2A	Q9BW72	376
CCDC32	NF1	P21359	375
CCDC32	RARA	P10276	369

IntAct

23 interactions, top by confidence:

A	B	Type	Score
AP2S1	AP2A2	psi-mi:“MI:0914”(association)	0.640
GTPBP3	CCDC32	psi-mi:“MI:0915”(physical association)	0.560
CCDC32	BDNF	psi-mi:“MI:0915”(physical association)	0.560
CCDC32	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.560
CCDC32	POT1	psi-mi:“MI:0915”(physical association)	0.510
HSPB1	CCDC32	psi-mi:“MI:0915”(physical association)	0.370
Lin7c	AMOTL2	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CCDC32	AP2A2	psi-mi:“MI:0914”(association)	0.350
AP2S1	FCHO1	psi-mi:“MI:0914”(association)	0.350
NDN	PABPC1	psi-mi:“MI:2364”(proximity)	0.270
POT1	CCDC32	psi-mi:“MI:0915”(physical association)	0.000
GTPBP3	CCDC32	psi-mi:“MI:0915”(physical association)	0.000
CCDC32	phnP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): C15orf57 (Two-hybrid), C15orf57 (Affinity Capture-MS), C15orf57 (Affinity Capture-MS), C15orf57 (Affinity Capture-MS), C15orf57 (Affinity Capture-RNA), C15orf57 (Two-hybrid), GTPBP3 (Two-hybrid), C15orf57 (Negative Genetic), C15orf57 (Affinity Capture-MS), C15orf57 (Affinity Capture-MS), AP2A2 (Affinity Capture-MS), AP2A1 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), NUDT9 (Affinity Capture-MS), AP2M1 (Affinity Capture-MS)

ESM2 similar proteins: A0MD28, A6YQT5, O36367, O56045, P03209, P03210, P03264, P04498, P05858, P05859, P06500, P0DJY0, P0DJZ9, P11806, P11807, P11823, P11824, P19811, P20867, P20886, P22745, P25247, P26627, P36714, P36856, Q00167, Q04561, Q05323, Q06502, Q1HVF8, Q1HVG0, Q2HR85, Q3KSS7, Q561K4, Q5XX03, Q65652, Q65956, Q68772, Q6UDG8, Q77DJ5

Diamond homologs: Q561K4, Q8BS39, Q9BV29, X1WGV5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	4
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1690313	NC_000015.10:g.40529942_40562524del	Pathogenic
2431643	NC_000015.10:g.(40529939_40562522)del	Pathogenic
988600	NM_001080792.4(CCDC32):c.27dup (p.Thr10fs)	Pathogenic
988601	NM_001080792.4(CCDC32):c.162_163dup (p.Glu55fs)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40557298:C:G	A107P	0.994
15:40554080:A:T	V150D	0.993
15:40557363:A:G	L85P	0.993
15:40554113:A:G	F139S	0.990
15:40562774:A:G	L81P	0.990
15:40557306:A:G	L104P	0.989
15:40554101:A:G	L143P	0.988
15:40554105:A:G	W142R	0.986
15:40554105:A:T	W142R	0.986
15:40557327:G:A	S97F	0.985
15:40557276:C:G	R114P	0.984
15:40554065:A:T	V155D	0.982
15:40554083:G:T	A149D	0.982
15:40562959:C:A	W19C	0.982
15:40562959:C:G	W19C	0.982
15:40554056:A:G	L158P	0.981
15:40554106:C:A	R141S	0.981
15:40554106:C:G	R141S	0.981
15:40562787:A:C	Y77D	0.981
15:40562961:A:G	W19R	0.981
15:40562961:A:T	W19R	0.981
15:40557306:A:T	L104Q	0.980
15:40557315:A:G	L101P	0.978
15:40554103:C:A	W142C	0.976
15:40554103:C:G	W142C	0.976
15:40557304:C:G	A105P	0.974
15:40562783:A:G	L78S	0.974
15:40557270:A:G	L116P	0.973
15:40557273:A:G	F115S	0.973
15:40557293:C:A	K108N	0.973

dbSNP variants (sampled 300 via entrez): RS1000006147 (15:40544734 T>A), RS1000087107 (15:40527725 G>A), RS1000091456 (15:40558673 G>A), RS1000262942 (15:40520905 A>G), RS1000308421 (15:40539337 G>C), RS1000318213 (15:40534063 A>G,T), RS1000380380 (15:40526908 A>AAAT), RS1000394426 (15:40539902 C>A,G), RS1000425517 (15:40540381 T>C,G), RS1000501075 (15:40553642 A>C,G), RS1000573308 (15:40553879 G>A,T), RS1000576064 (15:40564221 T>TA), RS1000610316 (15:40546339 G>A), RS1000647664 (15:40533781 G>A,T), RS1000749915 (15:40546842 C>T)

Disease associations

OMIM: gene MIM:618941 | disease phenotypes: MIM:619123

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiofacioneurodevelopmental syndrome	Strong	Autosomal recessive
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
cardiofacioneurodevelopmental syndrome	Moderate	AR

Mondo (2): cardiofacioneurodevelopmental syndrome (MONDO:0030873), syndromic intellectual disability (MONDO:0000508)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000411	Protruding ear
HP:0000582	Upslanted palpebral fissure
HP:0000601	Hypotelorism
HP:0001156	Brachydactyly
HP:0001263	Global developmental delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001629	Ventricular septal defect
HP:0001642	Pulmonic stenosis
HP:0001746	Asplenia
HP:0002808	Kyphosis
HP:0003363	Abdominal situs inversus
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0006695	Atrioventricular canal defect
HP:0007477	Abnormal dermatoglyphics
HP:0008386	Aplasia/Hypoplasia of the nails
HP:0008872	Feeding difficulties in infancy
HP:0012385	Camptodactyly
HP:0410030	Cleft lip

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression, increases abundance	2
Valproic Acid	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
NSC 689534	affects binding, increases expression	1
Bortezomib	increases expression	1
Copper	affects binding, increases expression	1
Methyl Methanesulfonate	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Vincristine	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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