C2CD2

Summary

C2CD2 (C2 calcium dependent domain containing 2, HGNC:1266) is a protein-coding gene on chromosome 21q22.3, encoding C2 domain-containing protein 2 (Q9Y426).

Located in cytosol and nucleus.

Source: NCBI Gene 25966 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 103 total — 1 pathogenic
• MANE Select transcript: NM_015500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1266
Approved symbol	C2CD2
Name	C2 calcium dependent domain containing 2
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	TMEM24L, DKFZP586F0422, C21orf258
Ensembl gene	ENSG00000157617
Ensembl biotype	protein_coding
OMIM	617581
Entrez	25966

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000329623, ENST00000380486, ENST00000449165, ENST00000467074, ENST00000478372, ENST00000482084, ENST00000482186, ENST00000490479, ENST00000890791

RefSeq mRNA: 2 — MANE Select: NM_015500 NM_015500, NM_199050

CCDS: CCDS13677, CCDS42933

Canonical transcript exons

ENST00000380486 — 14 exons

Exon	Start	End
ENSE00001787500	41885112	41889344
ENSE00002214448	41942147	41942245
ENSE00002277761	41953370	41954018
ENSE00003478085	41912332	41912440
ENSE00003496666	41918856	41918960
ENSE00003504516	41909459	41909523
ENSE00003550939	41905724	41905837
ENSE00003569108	41901622	41901749
ENSE00003580315	41914598	41914721
ENSE00003609495	41918105	41918227
ENSE00003616990	41906992	41907166
ENSE00003663241	41899053	41899362
ENSE00003664448	41907660	41907784
ENSE00003687664	41921972	41922085

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7630 / max 192.7964, expressed in 1719 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190571	3.3454	1455
190573	1.8586	1137
190572	1.0960	611
190570	0.4630	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.45	gold quality
adrenal cortex	UBERON:0001235	98.36	gold quality
left adrenal gland cortex	UBERON:0035825	98.28	gold quality
right adrenal gland	UBERON:0001233	98.27	gold quality
left adrenal gland	UBERON:0001234	98.16	gold quality
adrenal gland	UBERON:0002369	97.89	gold quality
adrenal tissue	UBERON:0018303	97.70	gold quality
tendon of biceps brachii	UBERON:0008188	94.02	gold quality
adipose tissue	UBERON:0001013	93.11	gold quality
spleen	UBERON:0002106	92.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.65	gold quality
coronary artery	UBERON:0001621	92.47	gold quality
connective tissue	UBERON:0002384	92.47	gold quality
right coronary artery	UBERON:0001625	92.46	gold quality
left coronary artery	UBERON:0001626	92.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.11	gold quality
upper leg skin	UBERON:0004262	91.94	gold quality
omental fat pad	UBERON:0010414	91.89	gold quality
peritoneum	UBERON:0002358	91.85	gold quality
parotid gland	UBERON:0001831	91.38	gold quality
dorsal root ganglion	UBERON:0000044	90.83	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	90.55	gold quality
ascending aorta	UBERON:0001496	90.35	gold quality
thoracic aorta	UBERON:0001515	90.28	gold quality
aorta	UBERON:0000947	89.86	gold quality
descending thoracic aorta	UBERON:0002345	89.63	gold quality
popliteal artery	UBERON:0002250	89.62	gold quality
tibial artery	UBERON:0007610	89.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting C2CD2, 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-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 3)

• The C2CD2/C21orf25 promoter is activated by Trichostatin A (TSA) treatment and by serum depletion according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
• Genotyping was accomplished on Infinium Human610-QUAD version 1. In the ilSIRENTE population, genetic variants in ZNF295 and C2CD2 (rs928874 and rs1788355) on chromosome 21q22.3, were significantly associated with the 4-meter gait speed (PMID:29158487)
• A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts. (PMID:39158698)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	c2cd2	ENSDARG00000105000
mus_musculus	C2cd2	ENSMUSG00000045975
rattus_norvegicus	C2cd2	ENSRNOG00000001621
drosophila_melanogaster	CG10737	FBGN0034420
caenorhabditis_elegans		WBGENE00020012

Paralogs (1): C2CD2L (ENSG00000172375)

Protein

Protein identifiers

C2 domain-containing protein 2 — Q9Y426 (reviewed: Q9Y426)

Alternative names: Transmembrane protein 24-like

All UniProt accessions (2): Q9Y426, H7BZB0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y426-1	1	yes
Q9Y426-2	2
Q9Y426-3	3

RefSeq proteins (2): NP_056315, NP_950251 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR039934	C2CD2/C2CD2L	Family
IPR040885	SMP_C2CD2L	Domain

Pfam: PF00168, PF18696

UniProt features (19 total): modified residue 5, sequence conflict 3, splice variant 2, sequence variant 2, domain 2, compositionally biased region 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y426-F1	62.52	0.08

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 (5): 445, 581, 60, 435, 441

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 182 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, ELVIDGE_HYPOXIA_DN, GENTILE_RESPONSE_CLUSTER_D3, CEBPB_01, ONKEN_UVEAL_MELANOMA_UP, WTGAAAT_UNKNOWN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GENTILE_UV_HIGH_DOSE_DN, DOUGLAS_BMI1_TARGETS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, ACTTTAT_MIR1425P, chr21q22, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular membrane-bounded organelle	1
cytoplasm	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2CD2	ZBTB21	Q9ULJ3	610
C2CD2	TM2D1	Q9BX74	508
C2CD2	ZNF805	Q5CZA5	505
C2CD2	PRDM15	P57071	488
C2CD2	ENDOD1	O94919	488
C2CD2	TMEM158	Q8WZ71	469
C2CD2	NOL9	Q5SY16	452
C2CD2	DSTN	P18282	425
C2CD2	RHBDL3	P58872	422
C2CD2	UBTD2	Q8WUN7	416
C2CD2	COL8A2	P25067	412
C2CD2	TMEM266	Q2M3C6	405
C2CD2	FAM228B	P0C875	398
C2CD2	TRDMT1	O14717	397
C2CD2	RCAN3	Q9UKA8	395

IntAct

36 interactions, top by confidence:

A	B	Type	Score
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
	DENND11	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
C2CD2	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350
PIGH	ILVBL	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
RAMP3	MGST3	psi-mi:“MI:0914”(association)	0.350
AGK	RAB29	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
P2RY8	BTAF1	psi-mi:“MI:0914”(association)	0.350
SLC2A8	AGPAT2	psi-mi:“MI:0914”(association)	0.350
CACNG4	TTI1	psi-mi:“MI:0914”(association)	0.350
FLRT1	ADGRL1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
POLD3	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC11A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC22A15	C2CD2L	psi-mi:“MI:0914”(association)	0.350
SLC67A1	LTN1	psi-mi:“MI:0914”(association)	0.350
SLC2A1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC2A8	AP3D1	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): DYNC1LI2 (Affinity Capture-MS), ARHGAP10 (Affinity Capture-MS), SEC14L1 (Affinity Capture-MS), ARHGAP26 (Affinity Capture-MS), ARHGAP26 (Affinity Capture-MS), ARHGAP10 (Affinity Capture-MS), SEC14L1 (Affinity Capture-MS), DYNC1LI2 (Affinity Capture-MS), DYNC1LI1 (Affinity Capture-MS), C2CD2 (Affinity Capture-RNA), C2CD2 (Proximity Label-MS), C2CD2 (Proximity Label-MS), C2CD2 (Affinity Capture-MS), C2CD2 (Proximity Label-MS), C2CD2 (Proximity Label-MS)

ESM2 similar proteins: A6QP06, D3ZAP3, E9Q3C1, E9Q555, O00443, O14523, O54786, O60303, O94966, P15304, P59438, P59729, Q14CH0, Q29RJ0, Q3ULZ2, Q5BIR3, Q5E9L4, Q5EB20, Q5PQS0, Q5R7R7, Q5RD34, Q5SW75, Q5T5Y3, Q5U228, Q5VUB5, Q60664, Q61194, Q63HN8, Q6NU22, Q6NU51, Q6WCQ1, Q76I79, Q7TNN8, Q7TSI1, Q80X80, Q811P8, Q8BJS7, Q8BV79, Q8TB24, Q8WYL5

Diamond homologs: E9Q3C1, O14523, Q80X80, Q9Y426

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	73
Likely benign	9
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526705	GRCh37/hg19 21q11.2-22.3(chr21:15041209-48097372)	Pathogenic

SpliceAI

2867 predictions. Top by Δscore:

Variant	Effect	Δscore
21:41905719:GTTA:G	donor_loss	1.0000
21:41905720:TTA:T	donor_loss	1.0000
21:41905721:TA:T	donor_loss	1.0000
21:41905722:A:C	donor_loss	1.0000
21:41905723:C:T	donor_loss	1.0000
21:41905837:TC:T	acceptor_loss	1.0000
21:41905838:C:CA	acceptor_loss	1.0000
21:41905838:C:CC	acceptor_gain	1.0000
21:41905839:T:G	acceptor_loss	1.0000
21:41906978:T:A	donor_gain	1.0000
21:41912324:AGACT:A	donor_loss	1.0000
21:41912325:GACT:G	donor_loss	1.0000
21:41912326:AC:A	donor_loss	1.0000
21:41912327:CTCAC:C	donor_loss	1.0000
21:41912328:TC:T	donor_loss	1.0000
21:41912329:CA:C	donor_loss	1.0000
21:41912330:A:AC	donor_gain	1.0000
21:41912330:ACA:A	donor_loss	1.0000
21:41912331:C:A	donor_loss	1.0000
21:41912331:C:CT	donor_gain	1.0000
21:41912331:CA:C	donor_gain	1.0000
21:41912331:CAA:C	donor_gain	1.0000
21:41912331:CAAG:C	donor_gain	1.0000
21:41912341:T:TA	donor_gain	1.0000
21:41912348:C:A	donor_gain	1.0000
21:41912436:GTGGC:G	acceptor_gain	1.0000
21:41912439:GCC:G	acceptor_loss	1.0000
21:41912441:C:CC	acceptor_gain	1.0000
21:41914719:GTT:G	acceptor_gain	1.0000
21:41914720:TT:T	acceptor_gain	1.0000

AlphaMissense

4493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:41901638:A:T	I515K	0.997
21:41901638:A:G	I515T	0.994
21:41901707:G:T	A492D	0.994
21:41907060:A:T	V417D	0.994
21:41907165:A:G	F382S	0.994
21:41889274:A:C	S647R	0.993
21:41889274:A:T	S647R	0.993
21:41889276:T:G	S647R	0.993
21:41914648:A:G	L265P	0.993
21:41901638:A:C	I515R	0.992
21:41909497:A:G	L327S	0.992
21:41909518:A:G	L320S	0.992
21:41909507:A:G	S324P	0.991
21:41912410:A:G	L292P	0.991
21:41918915:A:G	W180R	0.991
21:41918915:A:T	W180R	0.991
21:41901695:A:G	L496P	0.990
21:41901649:G:C	S511R	0.989
21:41901649:G:T	S511R	0.989
21:41901651:T:G	S511R	0.989
21:41907051:A:T	V420D	0.989
21:41907763:A:T	V347D	0.988
21:41953420:A:G	W77R	0.988
21:41953420:A:T	W77R	0.988
21:41907670:A:T	V378D	0.986
21:41953408:A:G	W81R	0.986
21:41953408:A:T	W81R	0.986
21:41953561:C:G	G30R	0.986
21:41901644:A:T	I513N	0.985
21:41914648:A:T	L265Q	0.985

dbSNP variants (sampled 300 via entrez): RS1000035183 (21:41898116 C>G,T), RS1000103514 (21:41939572 A>C), RS1000146681 (21:41934910 C>A,T), RS1000215240 (21:41892929 C>A,T), RS1000257640 (21:41924394 T>C), RS1000321617 (21:41954934 G>A,C), RS1000364699 (21:41944533 A>AAG), RS1000373769 (21:41922147 G>A,C,T), RS1000426170 (21:41955330 T>A), RS1000474745 (21:41903543 A>C), RS1000481061 (21:41935164 A>G), RS1000520514 (21:41922899 C>A,T), RS1000596555 (21:41929240 G>C), RS1000654959 (21:41917562 A>G), RS1000687255 (21:41954158 C>A,T)

Disease associations

OMIM: gene MIM:617581 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002198_19	Tuberculosis	2.000000e-07
GCST010397_87	Gut microbiota (bacterial taxa, rank normal transformation method)	9.000000e-06
GCST90002400_497	Plateletcrit	6.000000e-12
GCST90002402_637	Platelet count	6.000000e-11
GCST90007006_7	Gut microbiota relative abundance (unclassified genus belonging to family Erysipelotrichaceae)	8.000000e-06
GCST90007011_1	Gut microbiota relative abundance (unclassified genus belonging to family Erysipelotrichaceae)	6.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	8
trichostatin A	affects cotreatment, decreases expression	3
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tamoxifen	affects cotreatment, decreases expression, affects expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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