C2CD4C

Summary

C2CD4C (C2 calcium dependent domain containing 4C, HGNC:29417) is a protein-coding gene on chromosome 19p13.3, encoding C2 calcium-dependent domain-containing protein 4C (Q8TF44).

Predicted to be active in cytosol.

Source: NCBI Gene 126567 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_001136263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29417
Approved symbol	C2CD4C
Name	C2 calcium dependent domain containing 4C
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	NLF3
Ensembl gene	ENSG00000183186
Ensembl biotype	protein_coding
OMIM	610336
Entrez	126567

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000332235, ENST00000920287

RefSeq mRNA: 1 — MANE Select: NM_001136263 NM_001136263

CCDS: CCDS45890

Canonical transcript exons

ENST00000332235 — 2 exons

Exon	Start	End
ENSE00001290344	405445	408401
ENSE00001322986	409006	409147

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 86.11.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9457 / max 64.1136, expressed in 541 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177888	1.2894	475
177887	0.3905	223
177889	0.2658	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
anterior cingulate cortex	UBERON:0009835	86.11	gold quality
right frontal lobe	UBERON:0002810	85.66	gold quality
amygdala	UBERON:0001876	84.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.94	gold quality
hypothalamus	UBERON:0001898	82.03	gold quality
neocortex	UBERON:0001950	81.14	gold quality
frontal cortex	UBERON:0001870	80.73	gold quality
prefrontal cortex	UBERON:0000451	80.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.68	gold quality
cerebral cortex	UBERON:0000956	79.61	gold quality
temporal lobe	UBERON:0001871	79.48	gold quality
parotid gland	UBERON:0001831	78.16	gold quality
cerebellar vermis	UBERON:0004720	78.00	gold quality
apex of heart	UBERON:0002098	77.72	gold quality
gingival epithelium	UBERON:0001949	77.46	gold quality
nasal cavity epithelium	UBERON:0005384	76.30	gold quality
cortical plate	UBERON:0005343	75.97	gold quality
forebrain	UBERON:0001890	75.66	gold quality
superior frontal gyrus	UBERON:0002661	75.35	gold quality
Ammon’s horn	UBERON:0001954	74.21	gold quality
germinal epithelium of ovary	UBERON:0001304	73.91	gold quality
vena cava	UBERON:0004087	73.42	gold quality
gingiva	UBERON:0001828	73.41	gold quality
substantia nigra	UBERON:0002038	73.00	gold quality
brain	UBERON:0000955	72.96	gold quality
pons	UBERON:0000988	72.70	gold quality
midbrain	UBERON:0001891	72.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	72.42	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting C2CD4C, 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-5193	100.00	67.26	1744
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-4292	99.16	65.57	1767

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C2CD4C	ENSDARG00000079876
mus_musculus	C2cd4c	ENSMUSG00000045912
rattus_norvegicus	C2cd4c	ENSRNOG00000073081

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

C2 calcium-dependent domain-containing protein 4C — Q8TF44 (reviewed: Q8TF44)

Alternative names: Nuclear-localized factor 3, Protein FAM148C

All UniProt accessions (1): Q8TF44

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the C2CD4 family.

RefSeq proteins (1): NP_001129735* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR043549	C2C4C/C2C4D	Family

Pfam: PF00168

UniProt features (10 total): region of interest 4, modified residue 3, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF44-F1	65.88	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 (3): 262, 264, 273

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): chr19p13, MODULE_495, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, MARTENS_TRETINOIN_RESPONSE_UP, MIR7154_5P, MIR3928_3P, MIR6810_3P, MIR6801_3P, MIR331_3P, GSE13306_RA_VS_UNTREATED_TREG_DN, MANNO_MIDBRAIN_NEUROTYPES_HNBML1, MANNO_MIDBRAIN_NEUROTYPES_HDA, MANNO_MIDBRAIN_NEUROTYPES_HDA1, ZHONG_PFC_C3_ASTROCYTE

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2CD4C	RND1	Q92730	549
C2CD4C	R3HDM4	Q96D70	431
C2CD4C	CIMAP1D	Q3SX64	413
C2CD4C	IL1B	P01584	387
C2CD4C	SPMAP2	Q9P2T0	381
C2CD4C	FAM222A	Q5U5X8	358
C2CD4C	ZC3H15	Q8WU90	358
C2CD4C	FAM174C	Q9BVV8	358
C2CD4C	NFKB1	P19838	354
C2CD4C	SLC35A1	P78382	354
C2CD4C	ARHGAP45	Q92619	351
C2CD4C	BTF3L4	Q96K17	351
C2CD4C	ZNF594	Q96JF6	349
C2CD4C	TRIM23	P36406	343
C2CD4C	ZNF286A	Q9HBT8	335

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CTDSPL	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNJ2	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (29): C2CD4C (Proximity Label-MS), C2CD4C (Affinity Capture-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Proximity Label-MS), C2CD4C (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A2R8YCJ5, A2A699, A2AEV7, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NL88, A8MVW0, A9JSM3, B2RU40, B8ZZ34, C9JH25, D4A9R4, J3QNX5, P0CG09, P98077, Q0VD38, Q14761, Q17QH7, Q29RK8, Q2KJ18, Q2M3V2, Q3SX20, Q5BJT1, Q5HZJ5, Q5RKR3, Q5T442, Q64697, Q69YZ2, Q6PB97, Q6PCT2, Q6UXK2, Q6ZMQ8, Q6ZVH7, Q6ZW31, Q80XF7, Q8BLS7

Diamond homologs: A6NLJ0, B7Z1M9, P0CG09, Q2KJ18, Q5HZI2, Q8NCU7, Q8TF44, Q17RD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

321 predictions. Top by Δscore:

Variant	Effect	Δscore
19:409001:CTTA:C	donor_loss	1.0000
19:409002:TTA:T	donor_loss	1.0000
19:409003:TA:T	donor_loss	1.0000
19:409004:A:AC	donor_gain	1.0000
19:409004:A:AT	donor_loss	1.0000
19:409004:ACCTG:A	donor_gain	1.0000
19:409005:C:CT	donor_gain	1.0000
19:409005:CCTG:C	donor_gain	1.0000
19:409005:CCTGC:C	donor_gain	1.0000
19:409004:AC:A	donor_gain	0.9900
19:409005:CC:C	donor_gain	0.9900
19:409005:CCT:C	donor_gain	0.9900
19:408402:C:CC	acceptor_gain	0.9800
19:407179:C:CT	donor_gain	0.9700
19:407180:C:CT	donor_gain	0.9700
19:408198:T:C	acceptor_gain	0.9700
19:409008:G:A	donor_gain	0.9700
19:408399:CGT:C	acceptor_gain	0.9600
19:408401:TCT:T	acceptor_loss	0.9500
19:408402:C:T	acceptor_loss	0.9500
19:408403:T:G	acceptor_loss	0.9500
19:408398:GCGT:G	acceptor_gain	0.9400
19:408399:CGTC:C	acceptor_gain	0.9400
19:408198:T:TC	acceptor_gain	0.9300
19:408400:GT:G	acceptor_gain	0.9300
19:409000:ACTT:A	donor_loss	0.9100
19:407178:A:AC	donor_gain	0.8900
19:408397:AGCGT:A	acceptor_gain	0.8800
19:408398:GCGTC:G	acceptor_gain	0.8800
19:407668:G:GT	acceptor_gain	0.8600

AlphaMissense

2697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:408222:A:G	I47T	1.000
19:408207:A:T	I52N	0.999
19:408212:A:C	F50L	0.999
19:408212:A:T	F50L	0.999
19:408214:A:G	F50L	0.999
19:408222:A:C	I47S	0.999
19:408222:A:T	I47N	0.999
19:407193:A:T	L390H	0.998
19:407250:A:G	F371S	0.998
19:408207:A:G	I52T	0.998
19:408213:A:G	F50S	0.998
19:408219:G:T	P48H	0.998
19:408237:A:G	L42S	0.998
19:407232:A:G	F377S	0.997
19:407282:G:C	S360R	0.997
19:407282:G:T	S360R	0.997
19:407284:T:G	S360R	0.997
19:408207:A:C	I52S	0.997
19:408220:G:A	P48S	0.997
19:407249:G:C	F371L	0.996
19:407249:G:T	F371L	0.996
19:407251:A:G	F371L	0.996
19:407193:A:G	L390P	0.995
19:407237:G:C	F375L	0.995
19:407237:G:T	F375L	0.995
19:407238:A:G	F375S	0.995
19:407239:A:G	F375L	0.995
19:407250:A:C	F371C	0.995
19:407397:A:G	L322P	0.995
19:408204:G:T	P53H	0.995

dbSNP variants (sampled 300 via entrez): RS1000253997 (19:408392 G>A,T), RS1000410633 (19:405268 G>C), RS1000637195 (19:409118 G>A), RS1000752322 (19:405690 G>A), RS1000800469 (19:408565 AGGC>A), RS1000852490 (19:405175 G>A,C,T), RS1000854580 (19:405975 T>C), RS1000927672 (19:406168 G>A,T), RS1001205985 (19:405810 C>G), RS1001257488 (19:410268 G>A,T), RS1001731414 (19:410423 G>A), RS1002418320 (19:406480 C>A,G), RS1003097979 (19:408230 G>A,C,T), RS1003462864 (19:407083 G>A), RS1003527449 (19:410055 T>C)

Disease associations

OMIM: gene MIM:610336 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_109	Obesity-related traits	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004697	estradiol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
bisphenol F	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	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
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Estradiol	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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