CSDC2

Summary

CSDC2 (cold shock domain containing C2, HGNC:30359) is a protein-coding gene on chromosome 22q13.2, encoding Cold shock domain-containing protein C2 (Q9Y534). RNA-binding factor which binds specifically to the very 3’-UTR ends of both histone H1 and H3.3 mRNAs, encompassing the polyadenylation signal.

Predicted to enable mRNA 3’-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 27254 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 25 total — 1 pathogenic
• MANE Select transcript: NM_014460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30359
Approved symbol	CSDC2
Name	cold shock domain containing C2
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PIPPin
Ensembl gene	ENSG00000172346
Ensembl biotype	protein_coding
OMIM	617689
Entrez	27254

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000306149, ENST00000460790, ENST00000901850, ENST00000901851, ENST00000901852, ENST00000901853, ENST00000949647, ENST00000949648, ENST00000949649, ENST00000949650, ENST00000949651

RefSeq mRNA: 1 — MANE Select: NM_014460 NM_014460

CCDS: CCDS14019

Canonical transcript exons

ENST00000306149 — 4 exons

Exon	Start	End
ENSE00003993421	41574733	41576666
ENSE00003993422	41573655	41573777
ENSE00003993423	41561010	41561183
ENSE00003993426	41571843	41572141

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 98.79.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6677 / max 385.3783, expressed in 821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192486	3.4046	583
192484	2.8790	679
192485	0.1549	74
192482	0.1011	54
192483	0.0950	60
192487	0.0331	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.79	gold quality
right atrium auricular region	UBERON:0006631	98.35	gold quality
heart left ventricle	UBERON:0002084	98.14	gold quality
cardiac atrium	UBERON:0002081	98.10	gold quality
cardiac ventricle	UBERON:0002082	97.99	gold quality
right coronary artery	UBERON:0001625	97.80	gold quality
left adrenal gland cortex	UBERON:0035825	97.70	gold quality
right adrenal gland	UBERON:0001233	97.69	gold quality
left ovary	UBERON:0002119	97.56	gold quality
left adrenal gland	UBERON:0001234	97.55	gold quality
adrenal cortex	UBERON:0001235	97.47	gold quality
right adrenal gland cortex	UBERON:0035827	97.43	gold quality
right ovary	UBERON:0002118	97.34	gold quality
popliteal artery	UBERON:0002250	96.20	gold quality
tibial artery	UBERON:0007610	96.18	gold quality
heart	UBERON:0000948	96.07	gold quality
aorta	UBERON:0000947	95.60	gold quality
body of uterus	UBERON:0009853	95.58	gold quality
coronary artery	UBERON:0001621	95.42	gold quality
left coronary artery	UBERON:0001626	95.37	gold quality
cranial nerve II	UBERON:0000941	95.32	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.32	gold quality
descending thoracic aorta	UBERON:0002345	95.31	gold quality
endocervix	UBERON:0000458	95.27	gold quality
left ventricle myocardium	UBERON:0006566	95.14	gold quality
thoracic aorta	UBERON:0001515	94.98	gold quality
ascending aorta	UBERON:0001496	94.91	gold quality
cerebellar cortex	UBERON:0002129	94.60	gold quality
cerebellar hemisphere	UBERON:0002245	94.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting CSDC2, 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-4481	100.00	66.42	1669
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4745-5P	99.98	65.95	1028
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-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Literature-anchored findings (GeneRIF, showing 1)

• Uterine suppression of CSDC2 through intrauterine-injected-specific small interfering RNA (siRNA) led to abnormal decidualization in early pregnancy, with more extended antimesometrial area and with poor M development if compared with control siRNA-injected animals. These results suggest that CSDC2 could be a regulator during decidua development. (PMID:30078185)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	csdc2a	ENSDARG00000041323
danio_rerio	CSDC2	ENSDARG00000100167
mus_musculus	Csdc2	ENSMUSG00000042109
rattus_norvegicus	Csdc2	ENSRNOG00000005332
drosophila_melanogaster	CG9705	FBGN0036661

Paralogs (1): CARHSP1 (ENSG00000153048)

Protein

Protein identifiers

Cold shock domain-containing protein C2 — Q9Y534 (reviewed: Q9Y534)

Alternative names: RNA-binding protein PIPPin

All UniProt accessions (2): Q9Y534, H7C4E7

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding factor which binds specifically to the very 3’-UTR ends of both histone H1 and H3.3 mRNAs, encompassing the polyadenylation signal. Might play a central role in the negative regulation of histone variant synthesis in the developing brain.

Subcellular location. Nucleus. Cytoplasm.

RefSeq proteins (1): NP_055275* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002059	CSP_DNA-bd	Domain
IPR011129	CSD	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR019844	CSD_CS	Conserved_site
IPR052069	Ca-reg_mRNA-binding_domain	Family

Pfam: PF00313

UniProt features (5 total): chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y534-F1	78.82	0.54

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): 19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, SETLUR_PROSTATE_CANCER_TMPRSS2_ERG_FUSION_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, KIM_WT1_TARGETS_12HR_UP, MODULE_207, LEE_TARGETS_OF_PTCH1_AND_SUFU_DN, chr22q13

GO Biological Process (2): mRNA processing (GO:0006397), regulation of mRNA stability (GO:0043488)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
RNA processing	1
mRNA metabolic process	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
nucleic acid binding	1
mRNA binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSDC2	RBKS	Q9H477	654
CSDC2	DICER1	Q9UPY3	624
CSDC2	CDH1	P12830	604
CSDC2	MGAT3	Q09327	546
CSDC2	POLR3D	P05423	531
CSDC2	MGAM	O43451	511
CSDC2	SI	P14410	510
CSDC2	FXYD5	Q96DB9	497
CSDC2	MGAT5	Q09328	477
CSDC2	DDX28	Q9NUL7	471
CSDC2	NECTIN1	Q15223	430
CSDC2	PRSS53	Q2L4Q9	421
CSDC2	AKNAD1	Q5T1N1	417
CSDC2	STARD9	Q9P2P6	415
CSDC2	SNAI1	O95863	401

IntAct

22 interactions, top by confidence:

A	B	Type	Score
CSDC2	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.740
PPP2R1A	CSDC2	psi-mi:“MI:0915”(physical association)	0.740
PPP2R1A	CSDC2	psi-mi:“MI:0915”(physical association)	0.560
CSDC2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	CSDC2	psi-mi:“MI:0915”(physical association)	0.560
CSDC2	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.560
INCA1	CSDC2	psi-mi:“MI:0915”(physical association)	0.560
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
PIK3R1	CSDC2	psi-mi:“MI:0915”(physical association)	0.400
PPP4C	ISG15	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270
PPP2R1A	CSDC2	psi-mi:“MI:0915”(physical association)	0.000
CSDC2	INCA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): CSDC2 (Two-hybrid), CSDC2 (Two-hybrid), CSDC2 (Two-hybrid), INCA1 (Two-hybrid), CSDC2 (Proximity Label-MS)

ESM2 similar proteins: A0A0K3AV08, A6NIR3, A7KAX9, A9SY39, B9EHT4, O01700, O93375, P0C5J9, P34442, P49584, P91599, P92186, Q03607, Q3MHJ7, Q3V0G7, Q4FE47, Q567C6, Q5R686, Q5U243, Q5VUJ5, Q5VVW2, Q5VW22, Q61CX7, Q63430, Q66HD5, Q6GPD0, Q6NRL1, Q6P7W2, Q811P8, Q8BFX3, Q8BXK8, Q8BYR2, Q8CI96, Q8K4J2, Q8N3C7, Q8VHH5, Q91VY5, Q91YQ3, Q93367, Q96DZ5

Diamond homologs: A0R5E1, E0J1Q3, E0J500, E1WGN1, O30875, O67327, P0A352, P0A353, P0A354, P0A362, P0A363, P0A968, P0A969, P0A970, P0A971, P0A972, P0A973, P0A974, P0A975, P0A978, P0A979, P0A980, P0A981, P0A986, P0A987, P0A9X9, P0A9Y0, P0A9Y1, P0A9Y2, P0A9Y3, P0A9Y4, P0A9Y5, P0A9Y6, P0A9Y7, P0A9Y8, P0A9Y9, P0A9Z0, P0CL01, P27484, P36995

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062450	GRCh37/hg19 22q13.1-13.31(chr22:39044105-45794212)x3	Pathogenic

SpliceAI

859 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41573778:G:GG	donor_gain	1.0000
22:41574731:A:AG	acceptor_gain	1.0000
22:41574732:G:GG	acceptor_gain	1.0000
22:41577439:CC:C	acceptor_gain	1.0000
22:41577440:CC:C	acceptor_gain	1.0000
22:41573770:GTGTC:G	donor_gain	0.9900
22:41573771:TGTCT:T	donor_gain	0.9900
22:41573772:GTCTG:G	donor_gain	0.9900
22:41573776:GA:G	donor_gain	0.9900
22:41574728:GCCA:G	acceptor_loss	0.9900
22:41574729:CCA:C	acceptor_loss	0.9900
22:41574730:CA:C	acceptor_loss	0.9900
22:41574731:A:T	acceptor_loss	0.9900
22:41574732:G:A	acceptor_loss	0.9900
22:41574732:GC:G	acceptor_gain	0.9900
22:41574732:GCATC:G	acceptor_gain	0.9900
22:41574828:T:TA	donor_gain	0.9900
22:41574829:G:GA	donor_gain	0.9900
22:41574882:T:TA	donor_gain	0.9900
22:41577436:CCACC:C	acceptor_gain	0.9900
22:41577437:CACC:C	acceptor_gain	0.9900
22:41577437:CACCC:C	acceptor_gain	0.9900
22:41577441:CTG:C	acceptor_loss	0.9900
22:41577442:T:G	acceptor_loss	0.9900
22:41560894:G:GT	donor_gain	0.9800
22:41571841:AGAC:A	acceptor_gain	0.9800
22:41571842:GACG:G	acceptor_gain	0.9800
22:41572140:GC:G	donor_gain	0.9800
22:41572142:G:GG	donor_gain	0.9800
22:41573653:A:AG	acceptor_gain	0.9800

AlphaMissense

973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41572129:G:C	R55T	1.000
22:41572129:G:T	R55M	1.000
22:41572130:G:C	R55S	1.000
22:41572130:G:T	R55S	1.000
22:41573689:G:C	G71R	1.000
22:41573689:G:T	G71C	1.000
22:41573690:G:A	G71D	1.000
22:41573695:T:C	C73R	1.000
22:41573696:G:A	C73Y	1.000
22:41573697:T:G	C73W	1.000
22:41573704:T:C	F76L	1.000
22:41573705:T:C	F76S	1.000
22:41573705:T:G	F76C	1.000
22:41573706:C:A	F76L	1.000
22:41573706:C:G	F76L	1.000
22:41573719:G:C	G81R	1.000
22:41573720:G:A	G81D	1.000
22:41573720:G:T	G81V	1.000
22:41573722:C:G	H82D	1.000
22:41573723:A:C	H82P	1.000
22:41573725:G:C	G83R	1.000
22:41573726:G:A	G83D	1.000
22:41573726:G:T	G83V	1.000
22:41573728:T:C	F84L	1.000
22:41573730:C:A	F84L	1.000
22:41573730:C:G	F84L	1.000
22:41573732:T:A	I85N	1.000
22:41573732:T:C	I85T	1.000
22:41573732:T:G	I85S	1.000
22:41573761:T:C	F95L	1.000

dbSNP variants (sampled 300 via entrez): RS1000216959 (22:41564098 AAAAAG>A), RS1000235345 (22:41574928 T>C), RS1000327788 (22:41561353 T>G), RS1000339302 (22:41569252 CT>C,CTT), RS1000383062 (22:41567786 T>C), RS1000453798 (22:41569574 G>C,T), RS1000787899 (22:41565385 T>C,G), RS1000840666 (22:41573712 C>T), RS1000999292 (22:41572832 G>A), RS1001116345 (22:41561604 G>A), RS1001273808 (22:41568293 T>A), RS1001346773 (22:41573183 G>A), RS1001396018 (22:41573928 G>A), RS1001727995 (22:41567948 C>A,G,T), RS1002325995 (22:41565902 G>A,C,T)

Disease associations

OMIM: gene MIM:617689 | 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
GCST004946_20	Schizophrenia	1.000000e-12
GCST005232_52	Neuroticism	3.000000e-18
GCST007328_74	Alcohol consumption (drinks per week)	5.000000e-09
GCST008524_3	Bitter non-alcoholic beverage consumption	2.000000e-10
GCST010002_83	Refractive error	2.000000e-27
GCST010143_2	Meat-related diet	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0010093	bitter non-alcoholic beverage consumption measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	2
aminomethylphosphonic acid (AMPA)	decreases expression	1
beauvericin	affects cotreatment, decreases expression	1
trimellitic anhydride	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
enniatins	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Bleomycin	decreases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tamoxifen	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Raloxifene Hydrochloride	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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