PCID2

Summary

PCID2 (PCI domain containing 2, HGNC:25653) is a protein-coding gene on chromosome 13q34, encoding PCI domain-containing protein 2 (Q5JVF3). Required for B-cell survival through the regulation of the expression of cell-cycle checkpoint MAD2L1 protein during B cell differentiation. It is a common-essential gene (DepMap: required in 96.5% of cancer cell lines).

This gene encodes a component of the TREX-2 complex (transcription and export complex 2), which regulates mRNA export from the nucleus. This protein regulates expression of Mad2 mitotic arrest deficient-like 1, a cell division checkpoint protein. This protein also interacts with and stabilizes Brca2 (breast cancer 2) protein. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55795 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 64 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈6% of expected missense variation)
• Expression (HPA): Low tissue specificity — highest in testis, heart muscle, ovary
• GTEx eGene: eQTL in 16 tissues, sQTL in 9 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 96.5% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.17 (unconstrained)
• MANE Select transcript: NM_001127202
• Notable: 64 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25653
Approved symbol	PCID2
Name	PCI domain containing 2
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11305
Ensembl gene	ENSG00000126226
Ensembl biotype	protein_coding
OMIM	613713
Entrez	55795

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 26 nonsense_mediated_decay, 16 protein_coding, 9 protein_coding_CDS_not_defined

MANE Select: ENST00000337344

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 7, TSL 5: 6

ENST00000337344, ENST00000246505, ENST00000375457, ENST00000375459, ENST00000375477, ENST00000375479, ENST00000462653, ENST00000462853, ENST00000463102, ENST00000473462, ENST00000475433, ENST00000480971, ENST00000484641, ENST00000491548, ENST00000493650, ENST00000622406, ENST00000925339, ENST00000952596, ENST00000952597, ENST00000952598, ENST00000952599, ENST00000989719, ENST00000989720, ENST00000989721, ENST00000989722, ENST00000989723, ENST00001033094, ENST00001033095, ENST00001033096, ENST00001033097, ENST00001033098, ENST00001033100, ENST00001033101, ENST00001033102, ENST00001033103, ENST00001033104, ENST00001033106, ENST00001033107, ENST00001033109, ENST00001033110, ENST00001033112, ENST00001033113, ENST00001033114, ENST00001068313, ENST00001068314, ENST00001118638, ENST00001118639, ENST00001118640, ENST00001122433, ENST00001122434, ENST00001131588

RefSeq mRNA: 14 — MANE Select: NM_001127202 NM_001127202, NM_001127203, NM_001258213, NM_001320655, NM_001320656, NM_001320657, NM_001320659, NM_001320660, NM_001353091, NM_001353092, NM_001353093, NM_001353094, NM_001353095, NM_018386

CCDS: CCDS58301, CCDS58302, CCDS9532

Canonical transcript exons

ENST00000337344 — 14 exons

Exon	Start	End
ENSE00001419101	113177536	113178287
ENSE00001898558	113208599	113208669
ENSE00003468541	113200427	113200516
ENSE00003497525	113197178	113197243
ENSE00003499188	113185485	113185560
ENSE00003526446	113190872	113190975
ENSE00003541041	113198191	113198264
ENSE00003554023	113196181	113196222
ENSE00003557919	113195071	113195125
ENSE00003571281	113180158	113180231
ENSE00003614870	113178966	113179089
ENSE00003615920	113184346	113184487
ENSE00003644620	113179917	113180042
ENSE00003675012	113181130	113181230

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5998 / max 305.8048, expressed in 1808 samples.

Highest expression (Bgee): oocyte, secondary oocyte, ovary, testis, adrenal tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PCID2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	2.4e-22	+0.80	13:113200401:C:T
Testis	eqtl	3.4e-20	-0.29	13:113176145:C:T
Artery Tibial	eqtl	1.2e-13	-0.25	13:113167821:TCTTG:T
Whole Blood	eqtl	1.6e-13	+0.49	13:113168275:A:G
Artery Aorta	sqtl	5.9e-08	+0.57	13:113207071:C:T
Artery Aorta	eqtl	9.5e-08	-0.20	13:113179185:G:A
Artery Tibial	sqtl	2.3e-06	+0.41	13:113200401:C:T
Colon Sigmoid	eqtl	2.9e-06	-0.23	13:113205344:T:C
Cells Cultured fibroblasts	sqtl	9.8e-05	-0.24	13:113165607:T:A
Esophagus Muscularis	eqtl	4.5e-04	-0.18	13:113174098:C:T
Esophagus Gastroesophageal Junction	eqtl	4.9e-04	-0.21	13:113167821:TCTTG:T
Skin Sun Exposed Lower leg	eqtl	4.5e-03	+0.38	13:113825620:A:C
Cells Cultured fibroblasts	eqtl	8.4e-03	-0.19	13:112371798:G:C
Brain Cerebellum	sqtl	9.4e-03	-0.55	13:113165607:T:A
Nerve Tibial	eqtl	1.0e-02	+0.27	13:113587170:C:T
Thyroid	eqtl	1.0e-02	+0.63	13:113525938:C:G
Nerve Tibial	sqtl	1.7e-02	-1.23	13:113327655:T:G
Whole Blood	sqtl	1.9e-02	-0.81	13:113735772:C:T
Lung	eqtl	2.9e-02	+0.29	13:112809730:C:T
Muscle Skeletal	eqtl	3.0e-02	+0.18	13:113185691:TATTC:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
138335	26.7353	1805
138328	1.1065	413
138330	0.4685	254
138329	0.1288	56
138325	0.0767	26
138334	0.0610	4
138331	0.0229	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.06	gold quality
secondary oocyte	CL:0000655	96.26	gold quality
left ovary	UBERON:0002119	95.42	gold quality
right ovary	UBERON:0002118	95.24	gold quality
left testis	UBERON:0004533	94.68	gold quality
adrenal tissue	UBERON:0018303	94.53	gold quality
right testis	UBERON:0004534	94.49	gold quality
endocervix	UBERON:0000458	94.42	gold quality
body of uterus	UBERON:0009853	94.16	gold quality
cerebellar hemisphere	UBERON:0002245	93.85	gold quality
cerebellar cortex	UBERON:0002129	93.76	gold quality
left uterine tube	UBERON:0001303	93.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.73	gold quality
ectocervix	UBERON:0012249	93.71	gold quality
granulocyte	CL:0000094	93.65	gold quality
right coronary artery	UBERON:0001625	93.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.63	gold quality
right uterine tube	UBERON:0001302	93.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.58	gold quality
testis	UBERON:0000473	93.53	gold quality
right adrenal gland cortex	UBERON:0035827	93.53	gold quality
ascending aorta	UBERON:0001496	93.50	gold quality
thoracic aorta	UBERON:0001515	93.48	gold quality
adenohypophysis	UBERON:0002196	93.47	gold quality
body of pancreas	UBERON:0001150	93.40	gold quality
heart left ventricle	UBERON:0002084	93.30	gold quality
descending thoracic aorta	UBERON:0002345	93.29	gold quality
right adrenal gland	UBERON:0001233	93.26	gold quality
left adrenal gland cortex	UBERON:0035825	93.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.21	gold quality
right atrium auricular region	UBERON:0006631	93.20	gold quality
lower esophagus	UBERON:0013473	93.20	gold quality
ovary	UBERON:0000992	93.19	gold quality
aorta	UBERON:0000947	93.18	gold quality
left adrenal gland	UBERON:0001234	93.08	gold quality
cardiac ventricle	UBERON:0002082	93.08	gold quality
popliteal artery	UBERON:0002250	93.07	gold quality
tibial artery	UBERON:0007610	93.07	gold quality
left coronary artery	UBERON:0001626	92.89	gold quality
cerebellum	UBERON:0002037	92.77	gold quality
stromal cell of endometrium	CL:0002255	92.75	gold quality
heart	UBERON:0000948	92.69	gold quality
nerve	UBERON:0001021	92.67	gold quality
tibial nerve	UBERON:0001323	92.67	gold quality
skin of abdomen	UBERON:0001416	92.64	gold quality
minor salivary gland	UBERON:0001830	92.60	gold quality
adrenal gland	UBERON:0002369	92.55	gold quality
apex of heart	UBERON:0002098	92.50	gold quality
adrenal cortex	UBERON:0001235	92.48	gold quality
left lobe of thyroid gland	UBERON:0001120	92.47	gold quality
pituitary gland	UBERON:0000007	92.45	gold quality
skin of leg	UBERON:0001511	92.41	gold quality
body of stomach	UBERON:0001161	92.36	gold quality
right lobe of thyroid gland	UBERON:0001119	92.32	gold quality
coronary artery	UBERON:0001621	92.29	gold quality
islet of Langerhans	UBERON:0000006	92.26	gold quality
cardiac atrium	UBERON:0002081	92.18	gold quality
rectum	UBERON:0001052	92.01	gold quality
calcaneal tendon	UBERON:0003701	91.92	gold quality
omental fat pad	UBERON:0010414	91.83	gold quality
thyroid gland	UBERON:0002046	91.81	gold quality
peritoneum	UBERON:0002358	91.81	gold quality
right lung	UBERON:0002167	91.77	gold quality
esophagus	UBERON:0001043	91.71	gold quality
gastrocnemius	UBERON:0001388	91.65	gold quality
upper lobe of left lung	UBERON:0008952	91.58	gold quality
saliva-secreting gland	UBERON:0001044	91.52	gold quality
pancreas	UBERON:0001264	91.50	gold quality
gall bladder	UBERON:0002110	91.49	gold quality
spleen	UBERON:0002106	91.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.43	gold quality
vagina	UBERON:0000996	91.38	gold quality
muscle of leg	UBERON:0001383	91.33	gold quality
stomach	UBERON:0000945	91.31	gold quality
mucosa of stomach	UBERON:0001199	91.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.26	gold quality
ventricular zone	UBERON:0003053	91.11	gold quality
lymph node	UBERON:0000029	91.08	gold quality
right lobe of liver	UBERON:0001114	91.07	gold quality
fundus of stomach	UBERON:0001160	91.06	gold quality
upper lobe of lung	UBERON:0008948	91.05	gold quality
transverse colon	UBERON:0001157	90.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.95	gold quality
mouth mucosa	UBERON:0003729	90.90	gold quality
lower esophagus mucosa	UBERON:0035834	90.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.74	gold quality
esophagus mucosa	UBERON:0002469	90.66	gold quality
zone of skin	UBERON:0000014	90.62	gold quality
mucosa of transverse colon	UBERON:0004991	90.51	gold quality
prostate gland	UBERON:0002367	90.13	gold quality
adult organism	UBERON:0007023	90.04	gold quality
metanephros cortex	UBERON:0010533	90.02	gold quality
ganglionic eminence	UBERON:0004023	89.93	gold quality
leukocyte	CL:0000738	89.92	gold quality
small intestine	UBERON:0002108	89.91	gold quality
colon	UBERON:0001155	89.76	gold quality
monocyte	CL:0000576	89.74	gold quality
intestine	UBERON:0000160	89.73	gold quality
mononuclear cell	CL:0000842	89.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.86
E-HCAD-29	no	625.45

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	42.4	medium
Heart muscle	tissue	35.3	medium
Ovary	tissue	31.7	medium
Pons	tissue	26.4
Superior colliculi	tissue	25.9
Midbrain	tissue	25.6
Thalamus	tissue	25.5
Medulla oblongata	tissue	24.8
Spinal cord	tissue	24.4
Lymph node	tissue	24.2	low
Fallopian tube	tissue	23.8	medium
Substantia nigra	tissue	23.3
Tongue	tissue	22.8
Thymus	tissue	22.8
Salivary gland	tissue	22.4	low
Corpus callosum	tissue	22.4
Pituitary gland	tissue	22.0
Vagina	tissue	21.9	low
Adrenal gland	tissue	21.8	medium
Epididymis	tissue	21.7	medium
Tonsil	tissue	21.6	medium
Breast	tissue	21.5	medium
Cerebral cortex	tissue	21.3	low
Somatosensory cortex	tissue	21.3
Cervix	tissue	21.2	medium
Endometrium 1	tissue	20.5	medium
Hypothalamus	tissue	20.5
Smooth muscle	tissue	20.4	medium
Hippocampal formation	tissue	19.8
Periaqueductal gray	tissue	19.6
Cerebellum	tissue	19.5	low
Prostate	tissue	19.5	low
Skeletal muscle	tissue	19.0	medium
Thyroid gland	tissue	18.5	medium
Urinary bladder	tissue	18.4	medium
Occipital cortex	tissue	18.2
Seminal vesicle	tissue	18.1	medium
Parathyroid gland	tissue	18.0	low
Spleen	tissue	17.8	low
Frontal cortex	tissue	17.6
Motor cortex	tissue	17.4
Rectum	tissue	17.3	medium
Liver	tissue	17.2	low
Septum	tissue	17.2
Caudate putamen	tissue	17.1
Skin 1	tissue	16.7	low
Putamen	tissue	16.6
Ventral forebrain	tissue	16.5
Pancreas	tissue	16.4	medium
Prefrontal cortex	tissue	16.2
Adipose tissue	tissue	16.2	medium
Gallbladder	tissue	16.0	medium
Esophagus	tissue	15.7	low
Temporal cortex	tissue	15.7
Entorhinal cortex	tissue	15.5
Retrosplenial cortex	tissue	15.4
Colon	tissue	15.2	medium
Retrosplenial and cingulate cortex	tissue	15.2
Lung	tissue	15.1	medium
Kidney	tissue	15.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (26.3), Ventral spinal cord (24.4), Dorsal spinal cord (23.9), White matter (22.4), Dorsal hippocampus (19.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PCID2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-8069	97.05	66.79	718
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-454-5P	96.51	68.35	263
HSA-MIR-10A-3P	93.57	64.43	451

Functional genomics

gnomAD constraint: pLI 8.11e-05, LOEUF 1.17, missense Z 1.27 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000337344 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
13:113,178,201–113,185,555	226 / 296.5	0.76	no
13:113,185,556–113,190,931	11 / 32.0	0.34	yes (p 2.0e-04)
13:113,190,932–113,208,634	155 / 164.9	0.94	no

DepMap (CRISPR cell-line fitness): dependent in 96.5% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SU-DHL-10 (-2.195), PSN1 (-2.082), OCI-AML3 (-2.036), CL-11 (-2.025), HCC1187 (-1.93), MHH-ES-1 (-1.902), KP-4 (-1.832), NCI-H1694 (-1.822), LS1034 (-1.764), RL (-1.721), Capan-1 (-1.709), LU99 (-1.655), TALL-1 (-1.652), SKM-1 (-1.651), CAL-120 (-1.621).

Literature-anchored findings (GeneRIF, showing 8)

• validated occurrence of an unusual TG 3’ splice site in intron 2 (PMID:17672918)
• Pcid2 is present in the CBP/p300-EID1 complex to control the switch balance of mouse and human embryonic stem cells through modulation of EID1 degradation. (PMID:24167073)
• First discovery of specific novel functions for PCID2 other than mRNA export and components of the TREX-2 complex serve alternative shared roles in the regulation of nuclear transport and cell cycle progression. (PMID:24291146)
• Data show that PCI domain-containing protein 2 (Pcid2) controls lymphoid lineage commitment through the regulation of Snf2-related CREBBP activator protein (SRCAP) remodelling activity. (PMID:29138493)
• Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content. (PMID:32202298)
• Increased chemosensitivity via BRCA2-independent DNA damage in DSS1- and PCID2-depleted breast carcinomas. (PMID:34031538)
• A novel amplification gene PCI domain containing 2 (PCID2) promotes colorectal cancer through directly degrading a tumor suppressor promyelocytic leukemia (PML). (PMID:34625711)
• [PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation]. (PMID:38501418)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcid2	ENSDARG00000013802
mus_musculus	Pcid2	ENSMUSG00000038542
rattus_norvegicus	Pcid2	ENSRNOG00000025222
drosophila_melanogaster	PCID2	FBGN0036184
caenorhabditis_elegans		WBGENE00016171

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2443003) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 31 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased hematocrit	1
decreased neutrophil cell number	1
decreased monocyte cell number	1
decreased bone marrow cell number	1
abnormal enterocyte morphology	1
abnormal spleen morphology	1
spleen hypoplasia	1
small thymus	1
impaired hematopoiesis	1
premature death	1
abnormal eye morphology	1
abnormal definitive hematopoiesis	1
abnormal spleen capsule morphology	1
thrombocytopenia	1
decreased hematopoietic stem cell number	1
abnormal small intestine crypts of Lieberkuhn morphology	1
decreased spleen weight	1
decreased lymphocyte cell number	1
decreased follicular B cell number	1
decreased marginal zone B cell number	1
decreased mature B cell number	1
abnormal leukocyte morphology	1
abnormal spleen B cell follicle morphology	1
decreased spleen red pulp amount	1
decreased spleen white pulp amount	1

+6 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cryptococcus deneoformans JEC21	P0CR48	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CR49	100.0%	Diamond
Bos taurus	Q2TBN6	94.9%	Diamond
Xenopus laevis	Q5FWP8	88.2%	Diamond
Caenorhabditis briggsae	Q60YJ7	80.1%	Diamond
Fusarium graminearum PH-1	Q4IMN9	64.1%	Diamond
Neurospora crassa OR74A	Q7SD63	64.1%	Diamond
Aspergillus fumigatus Af293	Q4WJX0	58.4%	Diamond
Dictyostelium discoideum	Q54PX7	40.7%	Diamond
Mycosarcoma maydis	Q4P8T5	38.1%	Diamond
Schizosaccharomyces pombe 972h-	O13873	37.0%	Diamond
Arabidopsis thaliana	Q8GWE6	36.3%	Diamond
Debaryomyces hansenii CBS767	Q6BGR7	32.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR8075	ncRNA	102465874
LAMP1	protein-coding	3916
GRTP1	protein-coding	79774
CUL4A	protein-coding	8451
PROZ	protein-coding	8858
F10	protein-coding	2159
F10-AS2	protein-coding	102724474

Protein

Protein identifiers

PCI domain-containing protein 2 — Q5JVF3 (reviewed: Q5JVF3)

Alternative names: CSN12-like protein

All UniProt accessions (1): Q5JVF3

UniProt curated annotations — full annotation on UniProt →

Function. Required for B-cell survival through the regulation of the expression of cell-cycle checkpoint MAD2L1 protein during B cell differentiation. As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and transcription-associated genomic instability. Blocks the activity of the SRCAP chromatin remodeling complex by interacting with SRCAP complex member ZNHIT1 and inhibiting its interaction with the complex. This prevents the deposition of histone variant H2AZ1/H2A.Z at the nucleosomes of key lymphoid fate regulator genes which suppresses their expression and restricts lymphoid lineage commitment.

Subunit / interactions. Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153. Interacts with BRCA2. Interacts with SRCAP chromatin remodeling complex component ZNHIT1; the interaction results in inhibition of SRCAP complex activity, preventing the deposition of histone variant H2AZ1/H2A.Z to lymphoid fate regulator genes and restricting lymphoid lineage commitment.

Subcellular location. Cytoplasm. Nucleus. Nuclear pore complex.

Similarity. Belongs to the CSN12 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5JVF3-1	1	yes
Q5JVF3-2	2
Q5JVF3-3	3
Q5JVF3-4	4

RefSeq proteins (14): NP_001120674, NP_001120675, NP_001245142, NP_001307584, NP_001307585, NP_001307586, NP_001307588, NP_001307589, NP_001340020, NP_001340021, NP_001340022, NP_001340023, NP_001340024, NP_060856 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR045114	Csn12-like	Family

Pfam: PF01399

UniProt features (48 total): helix 25, sequence conflict 7, turn 5, strand 3, splice variant 3, modified residue 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

15 structures by resolution:

PDB	Title	Method	Resolution (Å)
3T5X	PCID2:DSS1 Structure	X-RAY DIFFRACTION	2.12
9RV1	Cryo-EM structure of the human UAP56-RNA - SAC3D1-PCID2-SEM1 complex	ELECTRON MICROSCOPY	2.62
9DLP	Cryo-EM structure of human TREX-2 complex bound to DDX39B(UAP56)	ELECTRON MICROSCOPY	2.79
9T6L	Cryo-EM structure of the human LENG8-PCID2-DSS1 complex bound to UAP56 and RRP1B	ELECTRON MICROSCOPY	2.9
9DLV	Cryo-EM structure of the human TREX-2.1 complex (LENG8/PCID2/DSS1) bound to DDX39B(UAP56)	ELECTRON MICROSCOPY	2.97
9T6N	Cryo-EM structure of the human GANP-PCID2-DSS1 complex bound to UAP56	ELECTRON MICROSCOPY	3
9DLR	Cryo-EM structure of the human TREX-2.1 complex (LENG8/PCID2/DSS1) bound to the …	ELECTRON MICROSCOPY	3.08
9UPC	Structure of human TREX-2	ELECTRON MICROSCOPY	3.14
9UPB	Structure of the human TREX-2 bound to UAP56	ELECTRON MICROSCOPY	3.41
28WZ	Cryo-EM structure of the human LENG8-PCID2-SEM1 complex	ELECTRON MICROSCOPY	3.5
8R7J	Cryo-EM structure of the human TREX-2 complex	ELECTRON MICROSCOPY	3.5
8R7K	Cryo-EM structure of the human UAP56 - TREX-2 complex	ELECTRON MICROSCOPY	3.5
28WY	Cryo-EM structure of the human SAC3D1-PCID2-SEM1 complex	ELECTRON MICROSCOPY	3.6
28XA	Cryo-EM structure of the human UAP56 NTD - LENG8-PCID2-SEM1 complex	ELECTRON MICROSCOPY	4.86
28XB	Cryo-EM structure of the human UAP56-RNA - LENG8-PCID2-SEM1 complex	ELECTRON MICROSCOPY	6.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JVF3-F1	95.64	0.93

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

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 (2)

Type	Positions
N-acetylalanine	2
Phosphoserine	45

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 213 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_B_CELL_ACTIVATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NUCLEAR_TRANSPORT, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, chr13q34, GOBP_REGULATION_OF_B_CELL_DIFFERENTIATION

GO Biological Process (11): post-transcriptional tethering of RNA polymerase II gene DNA at nuclear periphery (GO:0000973), transcription elongation by RNA polymerase II (GO:0006368), mRNA export from nucleus (GO:0006406), protein transport (GO:0015031), poly(A)+ mRNA export from nucleus (GO:0016973), positive regulation of B cell differentiation (GO:0045579), negative regulation of gene expression, epigenetic (GO:0045814), positive regulation of transcription by RNA polymerase II (GO:0045944), spleen development (GO:0048536), negative regulation of lymphoid progenitor cell differentiation (GO:1905457), mRNA transport (GO:0051028)

GO Molecular Function (3): double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear pore nuclear basket (GO:0044615), transcription export complex 2 (GO:0070390), nuclear pore (GO:0005643), protein-containing complex (GO:0032991)

GO top-level categories

34 GO namespaces:

Category	Terms
nuclear protein-containing complex	3
transcription by RNA polymerase II	2
cellular anatomical structure	2
transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery	1
DNA-templated transcription elongation	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
mRNA export from nucleus	1
B cell differentiation	1
regulation of B cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of B cell activation	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
hematopoietic or lymphoid organ development	1
lymphoid progenitor cell differentiation	1
negative regulation of hematopoietic progenitor cell differentiation	1
regulation of lymphoid progenitor cell differentiation	1
RNA transport	1
DNA binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear pore	1
nuclear envelope	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
poly(A)+ mRNA export from nucleus	BP	mutant phenotype
cytoplasm	CC	direct assay
nuclear pore nuclear basket	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
transcription export complex 2	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,072 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCID2	MCM3AP	O60318	796
PCID2	ENY2	Q9NPA8	769
PCID2	CUL4A	Q13619	734
PCID2	MAD2L1	Q13257	667
PCID2	MAD1L1	Q9Y6D9	667
PCID2	RAE1	P78406	663
PCID2	SEM1	Q6ZVN7	653
PCID2	BUB1B	O60566	641
PCID2	CCNB1	P14635	602
PCID2	CETN3	O15182	590
PCID2	CDK1	P06493	572
PCID2	DDB2	Q92466	563
PCID2	CETN2	P41208	556
PCID2	GRTP1	Q5TC63	555
PCID2	SLC9D1	Q6UWJ1	530

IntAct

Human interaction partners of PCID2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
SEM1	physical association	0.670	3
IKZF3	physical association	0.560	3
LENG8	physical association	0.560	3
BRF2	physical association	0.000	1
ILK	physical association	0.000	1
NEK6	physical association	0.000	1

BioGRID (117 interactions; top human partners by supporting records): SHFM1 (Two-hybrid; 6 records), DDX39B (Affinity Capture-MS; 4 records), CCNF (Affinity Capture-MS; 3 records), EID1 (Two-hybrid; 3 records), PML (Affinity Capture-MS; 3 records), CETN1 (Affinity Capture-MS; 2 records), CUL3 (Affinity Capture-MS; 2 records), MCM3AP (Affinity Capture-Western; 2 records), MYC (Affinity Capture-MS; 2 records), ADPRHL2 (Co-fractionation), AMBRA1 (Affinity Capture-MS), ATG16L1 (Affinity Capture-MS), ATG5 (Proximity Label-MS), AURKAIP1 (Proximity Label-MS), AXL (Proximity Label-MS)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
PCID2-ENY2-GANP-SEM1-CETN2 complex	5	SEM1, CETN2, ENY2, MCM3AP, PCID2
PCID2-ENY2-GANP-SEM1-CETN3 complex	5	CETN3, ENY2, MCM3AP, PCID2, SEM1

Disease & clinical

Genetic variants

Variant evidence for PCID2: 64 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1527786	GRCh37/hg19 13q31.1-34(chr13:79370012-115107733)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PCID2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,527):

Position(s)	Effect	Δscore	Sites
13:113178997	donor_gain	1.0000
13:113179090–113179091	acceptor_loss	1.0000	6
13:113179921	donor_gain	1.0000
13:113179933	donor_gain	1.0000
13:113180043–113180044	acceptor_loss	1.0000	5
13:113184345	donor_loss	1.0000	2
13:113198189–113198190	donor_loss	1.0000	5
13:113198265–113198266	acceptor_loss	1.0000	4
13:113198270–113198271	acceptor_gain	1.0000	2
13:113178288–113178289	acceptor_loss	0.9900	6

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000135
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000429
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000783
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000928

Disease associations

OMIM: gene MIM:613713 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST004630_246	Mean corpuscular hemoglobin	3e-14
GCST004602_22	Mean corpuscular volume	2e-10
GCST008103_61	Bipolar disorder	1e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725175 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecule by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 5 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	Kd	90	nM	MOLIBRESIB
6.58	IC50	260	nM	MOLIBRESIB
5.72	Kd	1923	nM	CHEMBL3752910
5.72	ED50	1923	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 11 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179187: Binding affinity against PCID2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0900	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148945: Binding affinity to human PCID2 incubated for 45 mins by Kinobead based pull down assay	kd	1.9226	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Valproic Acid	decreases expression, decreases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cannabidiol	decreases expression	1
Formaldehyde	decreases expression	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651987	Binding	Binding affinity to human PCID2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PCID2 across ~30M SureChEMBL compounds — explore on Sugi Predict.