PIMREG

Summary

PIMREG (PICALM interacting mitotic regulator, HGNC:25483) is a protein-coding gene on chromosome 17p13.2, encoding Protein PIMREG (Q9BSJ6). During mitosis, may play a role in the control of metaphase-to-anaphase transition.

Predicted to be involved in cell division. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 54478 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_019013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25483
Approved symbol	PIMREG
Name	PICALM interacting mitotic regulator
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10156, FLJ10491, CATS, RCS1
Ensembl gene	ENSG00000129195
Ensembl biotype	protein_coding
OMIM	617611
Entrez	54478

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000250056, ENST00000570337, ENST00000571373, ENST00000571572, ENST00000572447, ENST00000572595, ENST00000573385, ENST00000573557, ENST00000576056, ENST00000851328, ENST00000924241, ENST00000924242, ENST00000924243, ENST00000924244, ENST00000924245, ENST00000924246, ENST00000924247, ENST00000924248, ENST00000924249, ENST00000924250, ENST00000924251

RefSeq mRNA: 2 — MANE Select: NM_019013 NM_001195228, NM_019013

CCDS: CCDS32541, CCDS56016

Canonical transcript exons

ENST00000572447 — 6 exons

Exon	Start	End
ENSE00001371976	6445076	6445404
ENSE00002638414	6444455	6444488
ENSE00002661893	6450362	6451469
ENSE00003481949	6449312	6449407
ENSE00003645907	6447463	6447758
ENSE00003668179	6450028	6450072

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8740 / max 175.6751, expressed in 1268 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159052	8.6394	1141
159051	5.2346	1076

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.61	gold quality
ganglionic eminence	UBERON:0004023	95.38	gold quality
embryo	UBERON:0000922	93.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.78	gold quality
mucosa of transverse colon	UBERON:0004991	80.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.94	gold quality
stromal cell of endometrium	CL:0002255	78.24	gold quality
rectum	UBERON:0001052	72.77	gold quality
lower esophagus mucosa	UBERON:0035834	72.73	gold quality
spleen	UBERON:0002106	71.93	gold quality
adrenal tissue	UBERON:0018303	71.49	gold quality
right adrenal gland	UBERON:0001233	71.47	gold quality
cartilage tissue	UBERON:0002418	70.83	gold quality
esophagus mucosa	UBERON:0002469	69.93	gold quality
left adrenal gland	UBERON:0001234	69.53	gold quality
right adrenal gland cortex	UBERON:0035827	68.94	gold quality
left adrenal gland cortex	UBERON:0035825	68.40	gold quality
bone marrow	UBERON:0002371	67.58	gold quality
adrenal gland	UBERON:0002369	66.78	gold quality
adrenal cortex	UBERON:0001235	66.54	gold quality
amniotic fluid	UBERON:0000173	66.09	gold quality
buccal mucosa cell	CL:0002336	66.05	gold quality
thymus	UBERON:0002370	65.74	silver quality
tibia	UBERON:0000979	65.34	silver quality
transverse colon	UBERON:0001157	64.84	gold quality
smooth muscle tissue	UBERON:0001135	64.00	gold quality
vermiform appendix	UBERON:0001154	62.26	gold quality
duodenum	UBERON:0002114	62.21	gold quality
bone marrow cell	CL:0002092	61.76	gold quality
ileal mucosa	UBERON:0000331	61.52	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	560.25
E-HCAD-10	yes	37.26
E-HCAD-13	yes	22.59
E-HCAD-5	yes	17.84
E-MTAB-9388	yes	11.66
E-MTAB-7037	no	204.76
E-CURD-10	no	28.78
E-ANND-3	no	1.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting PIMREG, 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-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-296-5P	97.61	64.02	851

Literature-anchored findings (GeneRIF, showing 12)

• Moreover, we showed that CATS and KIS antagonize the transactivation capacity of CALM/AF10.In summary, our results show that CATS interacts with and is a substrate for KIS, suggesting that KIS regulates CATS function (PMID:23419774)
• Silencing of CATS (FAM64A) protein in U937 cell line resulted in somewhat reduced proliferation, altered cell cycle progression and lower migratory ability in vitro; however was not sufficient to inhibit tumor growth in xenotransplant model. (PMID:27588395)
• Study provides evidence that high FAM64A mRNA expression is an independent risk factor for poor prognosis in pancreatic cancer. (PMID:30695070)
• High expression of FAM64A is associated with advanced clinical grade, metastasis and unfavorable prognosis in breast cancer. Over-expressing FAM64A promotes breast cancer cell proliferation and migration. (PMID:30979502)
• PIMREG promotes breast cancer aggressiveness via disrupting the NF-kappaB/IkappaBalpha negative feedback loop, which suggests that PIMREG might be a valuable prognostic factor and potential target for diagnosis and therapy of metastatic breast cancer. (PMID:30979686)
• FAM64A plays an important role in the proliferation and migration of breast cancer cells, which might serve as a potential target for breast cancer treatment. (PMID:31264076)
• FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p). (PMID:32932948)
• Molecular pathogenesis of breast cancer: impact of miR-99a-5p and miR-99a-3p regulation on oncogenic genes. (PMID:33177704)
• FAM64A is an androgen receptor-regulated feedback tumor promoter in prostate cancer. (PMID:34215720)
• Excessive activation of HOXB13/PIMREG axis promotes hepatocellular carcinoma progression and drug resistance. (PMID:35878427)
• Cell Cycle-Related FAM64A Could be Activated by TGF-beta Signaling to Promote Glioma Progression. (PMID:37081231)
• A bioinformatics analysis of the clinicopathological and prognostic significance of FAM64A mRNA expression in gynecological cancers. (PMID:37227120)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pimreg	ENSMUSG00000020808
rattus_norvegicus	Pimregl1	ENSRNOG00000008040
rattus_norvegicus	Pimregl1	ENSRNOG00000016710

Protein

Protein identifiers

Protein PIMREG — Q9BSJ6 (reviewed: Q9BSJ6)

Alternative names: CALM-interactor expressed in thymus and spleen, PICALM-interacting mitotic regulator, Regulator of chromosome segregation protein 1

All UniProt accessions (7): Q9BSJ6, A0A0S2Z5C7, A0A0S2Z5F0, I3L156, I3L2R2, I3L419, I3L427

UniProt curated annotations — full annotation on UniProt →

Function. During mitosis, may play a role in the control of metaphase-to-anaphase transition.

Subunit / interactions. Isoform 1 and isoform 2 interact with PICALM; this interaction may target PICALM to the nucleus. During mitosis, associates with HDAC2 and MTA2 subunits of the chromatin-remodeling NuRD complex; this association is strongest at prometaphase and decreases as the cell progresses through metaphase and anaphase.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Expressed in thymus (at protein level). Detected in spleen, colon, ovary and small intestines.

Post-translational modifications. Ubiquitinated by the anaphase-promoting complex/cyclosome (APC/C) complex in the presence of FZR1, leading to its degradation by the proteasome during mitotic exit. However, degradation is not essential for normal mitotic progression within a single cell cycle.

Domain organisation. The N-terminal destruction box 2 (D-box 2) is required for APC/C ubiquitination and proteasomal degradation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSJ6-1	1	yes
Q9BSJ6-2	2

RefSeq proteins (2): NP_001182157, NP_061886* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009932	RCS1	Family

Pfam: PF07326

UniProt features (22 total): modified residue 6, mutagenesis site 4, compositionally biased region 3, region of interest 2, sequence conflict 2, short sequence motif 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSJ6-F1	60.62	0.09

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 (6): 129, 131, 199, 201, 11, 16

Mutagenesis-validated functional residues (4):

Position	Phenotype
14–17	weak reduction in ubiquitination. complete loss of ubiquitination; when associated with 53-a–a-56.
53–56	great reduction in ubiquitination. complete loss of ubiquitination; when associated with 14-a–a-17.
129	no effect on phosphorylation.
131	reduced phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, FISCHER_G2_M_CELL_CYCLE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, VANTVEER_BREAST_CANCER_ESR1_DN, MARKEY_RB1_ACUTE_LOF_UP, MODULE_48, MODULE_95, LOPEZ_MESOTHELIOMA_SURVIVAL_OVERALL_DN, KOBAYASHI_EGFR_SIGNALING_24HR_DN

GO Biological Process (1): cell division (GO:0051301)

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

GO Cellular Component (3): nucleoplasm (GO:0005654), nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular process	1
binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIMREG	BUB1	O43683	595
PIMREG	CCNB2	O95067	560
PIMREG	GAS2L3	Q86XJ1	545
PIMREG	PICALM	Q13492	544
PIMREG	CDK1	P06493	530
PIMREG	CDCA3	Q99618	513
PIMREG	NUF2	Q9BZD4	509
PIMREG	TTK	P33981	507
PIMREG	CKAP5	Q14008	488
PIMREG	CKAP2	Q8WWK9	488
PIMREG	NCAPD2	Q15021	476
PIMREG	PSRC1	Q6PGN9	474
PIMREG	KIF20B	Q96Q89	469
PIMREG	DLGAP5	Q15398	459
PIMREG	CCNB1	P14635	456

IntAct

92 interactions, top by confidence:

A	B	Type	Score
PIMREG	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	PIMREG	psi-mi:“MI:0915”(physical association)	0.720
KRT40	PIMREG	psi-mi:“MI:0915”(physical association)	0.720
PIMREG	CEP70	psi-mi:“MI:0915”(physical association)	0.720
PIMREG	KRT40	psi-mi:“MI:0915”(physical association)	0.720
CEP70	PIMREG	psi-mi:“MI:0915”(physical association)	0.720
PIMREG	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
PIMREG	MTA2	psi-mi:“MI:0914”(association)	0.600

BioGRID (70): FAM64A (Two-hybrid), FAM64A (Two-hybrid), FAM64A (Two-hybrid), AGTRAP (Two-hybrid), CEP70 (Two-hybrid), SSX2IP (Two-hybrid), KRT40 (Two-hybrid), TDRD7 (Affinity Capture-MS), TTC19 (Affinity Capture-MS), ACAD11 (Affinity Capture-MS), PICALM (Affinity Capture-MS), FAM64A (Reconstituted Complex), FAM64A (Reconstituted Complex), TDRD7 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVZ6, A5D7I0, A6H7B4, A6NDZ8, A6NE82, A6NJ08, A6NJB7, A6NJI1, A6NL46, A6QP24, A8MUA0, A8MUI8, A8MV72, A8MX80, B2RW88, O94850, P0C6A0, P24097, P50617, Q0P5M0, Q0VD86, Q2KIL8, Q3B8N5, Q3SY00, Q3SYA9, Q3UN58, Q5BMD4, Q5JTZ5, Q5RBE4, Q5VZ46, Q66MI6, Q68US1, Q6GQV0, Q6PAC4, Q80TS7, Q80VY2, Q8BFY7, Q8BII1, Q8IXW0, Q8K2F3

Diamond homologs: Q8BFY7, Q9BSJ6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PIMREG	down-regulates	PICALM	relocalization
UHMK1	up-regulates	PIMREG	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
17:6445376:C:G	donor_gain	1.0000
17:6447462:GAGA:G	acceptor_gain	1.0000
17:6449310:A:AG	acceptor_gain	1.0000
17:6449311:G:GG	acceptor_gain	1.0000
17:6449311:GCGA:G	acceptor_gain	1.0000
17:6444484:GTCGG:G	donor_gain	0.9900
17:6444485:TCGGG:T	donor_loss	0.9900
17:6444487:GG:G	donor_gain	0.9900
17:6444488:GG:G	donor_gain	0.9900
17:6444488:GGT:G	donor_loss	0.9900
17:6444489:G:A	donor_loss	0.9900
17:6444489:G:GG	donor_gain	0.9900
17:6444490:TGAG:T	donor_loss	0.9900
17:6444491:GAGT:G	donor_loss	0.9900
17:6444922:G:GT	donor_gain	0.9900
17:6445072:CCA:C	acceptor_loss	0.9900
17:6445074:A:AG	acceptor_gain	0.9900
17:6445074:A:C	acceptor_loss	0.9900
17:6445074:AG:A	acceptor_gain	0.9900
17:6445075:G:GT	acceptor_gain	0.9900
17:6445075:GG:G	acceptor_gain	0.9900
17:6447461:A:AG	acceptor_gain	0.9900
17:6447462:G:A	acceptor_loss	0.9900
17:6447462:G:GG	acceptor_gain	0.9900
17:6447462:GA:G	acceptor_gain	0.9900
17:6447462:GAGAA:G	acceptor_gain	0.9900
17:6449306:A:AG	acceptor_gain	0.9900
17:6449307:T:G	acceptor_gain	0.9900
17:6449307:TGCA:T	acceptor_loss	0.9900
17:6449308:GCA:G	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000309452 (17:6444045 T>C), RS1000592579 (17:6444908 G>C), RS1000622949 (17:6450023 T>C), RS1000648363 (17:6445190 A>G), RS1000760513 (17:6443903 C>T), RS1000834317 (17:6445147 C>G,T), RS1000893289 (17:6448810 G>A), RS1001088038 (17:6443513 C>T), RS1002265319 (17:6446278 G>C), RS1002553029 (17:6446608 C>A,T), RS1002909827 (17:6451404 A>G), RS1003430097 (17:6450551 G>A), RS1003833062 (17:6443366 T>G), RS1003911593 (17:6450866 C>A), RS1004270166 (17:6448172 C>G)

Disease associations

OMIM: gene MIM:617611 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009163_3	Hormone measurements	6.000000e-09
GCST009391_856	Metabolite levels	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0010533	sorbitol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tunicamycin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
diallyl trisulfide	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	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	decreases expression	1
palbociclib	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Dasatinib	decreases expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

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