PUM2

Summary

PUM2 (pumilio RNA binding family member 2, HGNC:14958) is a protein-coding gene on chromosome 2p24.1, encoding Pumilio homolog 2 (Q8TB72). Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3’-UTR of mRNA targets.

This gene encodes a protein that belongs to a family of RNA-binding proteins. The encoded protein functions as a translational repressor during embryonic development and cell differentiation. This protein is also thought to be a positive regulator of cell proliferation in adipose-derived stem cells. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 23369 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 133 total
• Druggable target: yes
• MANE Select transcript: NM_015317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14958
Approved symbol	PUM2
Name	pumilio RNA binding family member 2
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	PUMH2, KIAA0235
Ensembl gene	ENSG00000055917
Ensembl biotype	protein_coding
OMIM	607205
Entrez	23369

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 49 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000338086, ENST00000361078, ENST00000420234, ENST00000424110, ENST00000429419, ENST00000432105, ENST00000440577, ENST00000442400, ENST00000446940, ENST00000704930, ENST00000899119, ENST00000899120, ENST00000899121, ENST00000899122, ENST00000899123, ENST00000899124, ENST00000899125, ENST00000899126, ENST00000899127, ENST00000899128, ENST00000899129, ENST00000899130, ENST00000899131, ENST00000899132, ENST00000899133, ENST00000899134, ENST00000899135, ENST00000899136, ENST00000899137, ENST00000899138, ENST00000899139, ENST00000899140, ENST00000899141, ENST00000899142, ENST00000899143, ENST00000899144, ENST00000899145, ENST00000899146, ENST00000899147, ENST00000899148, ENST00000899149, ENST00000919026, ENST00000919027, ENST00000919028, ENST00000919029, ENST00000919030, ENST00000955768, ENST00000955769, ENST00000955770, ENST00000955771, ENST00000955772, ENST00000955773, ENST00000955774

RefSeq mRNA: 15 — MANE Select: NM_015317 NM_001282752, NM_001282790, NM_001282791, NM_001352917, NM_001352918, NM_001352919, NM_001352920, NM_001352923, NM_001352925, NM_001352926, NM_001352927, NM_001352928, NM_001352929, NM_001352930, NM_015317

CCDS: CCDS1698, CCDS92717

Canonical transcript exons

ENST00000361078 — 21 exons

Exon	Start	End
ENSE00000432849	20283343	20283486
ENSE00000432856	20255216	20255341
ENSE00000432857	20254863	20254984
ENSE00000715476	20256033	20256170
ENSE00000715591	20263193	20263460
ENSE00000715661	20278583	20278819
ENSE00000802769	20260337	20260466
ENSE00000802771	20282947	20283231
ENSE00000802773	20290652	20290790
ENSE00000802774	20294376	20294518
ENSE00000802775	20297553	20297678
ENSE00000802776	20307978	20308071
ENSE00001145371	20308314	20308584
ENSE00001377208	20258243	20258371
ENSE00001783521	20253822	20254014
ENSE00003461886	20327310	20327378
ENSE00003473137	20312236	20312423
ENSE00003612522	20318537	20318645
ENSE00003682751	20311494	20311663
ENSE00003992716	20350597	20350844
ENSE00003992717	20248737	20251716

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0179 / max 221.2205, expressed in 1793 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27131	12.7025	1773
27129	2.0452	908
27130	1.3073	793
27128	0.4700	261
27133	0.2703	105
27132	0.2225	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	97.81	gold quality
cortical plate	UBERON:0005343	97.59	gold quality
middle temporal gyrus	UBERON:0002771	97.36	gold quality
ventricular zone	UBERON:0003053	97.28	gold quality
tibia	UBERON:0000979	97.03	gold quality
calcaneal tendon	UBERON:0003701	96.98	gold quality
upper leg skin	UBERON:0004262	96.61	gold quality
cerebellar vermis	UBERON:0004720	96.55	gold quality
epithelium of nasopharynx	UBERON:0001951	96.47	gold quality
ganglionic eminence	UBERON:0004023	96.36	gold quality
bronchial epithelial cell	CL:0002328	96.24	gold quality
amniotic fluid	UBERON:0000173	96.22	gold quality
hair follicle	UBERON:0002073	96.08	gold quality
tonsil	UBERON:0002372	96.01	gold quality
postcentral gyrus	UBERON:0002581	95.91	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.89	gold quality
skin of hip	UBERON:0001554	95.87	gold quality
bone marrow cell	CL:0002092	95.85	gold quality
visceral pleura	UBERON:0002401	95.78	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.69	gold quality
jejunal mucosa	UBERON:0000399	95.67	gold quality
epithelium of bronchus	UBERON:0002031	95.63	gold quality
parietal lobe	UBERON:0001872	95.49	gold quality
bronchus	UBERON:0002185	95.49	gold quality
superficial temporal artery	UBERON:0001614	95.37	gold quality
ileal mucosa	UBERON:0000331	95.35	gold quality
esophagus squamous epithelium	UBERON:0006920	95.35	gold quality
superior frontal gyrus	UBERON:0002661	95.32	gold quality
epithelium of mammary gland	UBERON:0003244	95.30	gold quality
pleura	UBERON:0000977	95.21	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.19
E-ENAD-27	yes	3.78
E-MTAB-7249	no	806.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

254 targeting PUM2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181

Literature-anchored findings (GeneRIF, showing 36)

• PUM2 as a component of conserved cellular machinery that may be required for germ cell development. (PMID:12511597)
• PUM2 and DAZL, are capable of binding the same mRNA sequences in the 3’UTR of human SDAD1 mRNA. (PMID:15607425)
• P2P-R expression may be translationally regulated by PUM2 (PMID:15617101)
• PUMILIO mediated translational regulation may be universally used in developmental processes of the human body. (PMID:16967088)
• Variation in the PUMILIO2 gene is very low and it seems improbable that mutations of this gene significantly contribute to male infertility in humans. (PMID:17154300)
• Data found that PUMILIO2 interacts also with SNAPIN, a modulator of SNARE complex assembly, which is involved in vesicle trafficking. (PMID:19168546)
• Three distinct modes of target RNA binding by PUM2 around the fifth mRNA base were observed. (PMID:21397187)
• in mitosis, PUM2 physically associates with Aurora-A to ensure enough active Aurora-A at centrosomes for mitotic entry (PMID:21589936)
• PUM2 does not repress differentiation of adipose-derived stem cells (ASCs) but rather is involved in the positive control of ASCs division and proliferation. (PMID:21649561)
• NANOS1-PUMILIO2 complex, together with GEMIN3 and small noncoding RNAs, possibly regulate mRNA translation within the chromatoid body of the human germ cells. (PMID:21800163)
• Mammalian PUM2-Ago-eEF1A inhibited translation of nonadenylated and polyadenylated reporter mRNAs in vitro. (PMID:22231398)
• human Pumilio homologs Pum 1 and Pum 2 repress the translation of E2F3 by binding to the E2F3 3’ untranslated region (UTR) and also enhance the activity of multiple E2F3 targeting microRNAs (miRNAs) (PMID:22345517)
• Pumilios (including PUM1 and PUM2) are RNA-binding proteins with Puf domains made up of 8 poorly conserved Puf repeats, 3 helix bundles arranged in rainbow architecture, where each repeat recognizes a single base of the RNA-binding sequence. [REVIEW] (PMID:26517885)
• Identification of NORAD-interacting proteins revealed that this lncRNA functions as a multivalent binding platform for PUM proteins, with the capacity to sequester a significant fraction of the total cellular pool of PUM1 and PUM2. Studies reveal unanticipated roles for a lncRNA and PUMILIO proteins in the maintenance of genomic stability. (PMID:26724866)
• A recent paper by the Mendell group identifies NORAD, a novel lncRNA that is regulated in response to DNA damage and plays a key role in maintaining genome integrity by modulating the activity the RNA binding proteins PUM2 and PUM1. (PMID:27157388)
• The study shows that pseudouridine and N(6)-methyladenosine weaken the binding of the human single-stranded RNA binding protein Pumilio 2 (hPUM2) to its consensus motif. (PMID:28138061)
• results reveal a novel regulatory pathway, underscoring a previously unknown and interconnected key role of PUM1/2 and FOXP1 in regulating normal hematopoietic stem/progenitor cell and leukemic cell growth. (PMID:28232582)
• Data indicate that RNAs-including mRNAs and non-coding RNAs-that are functionally regulated by Pumilio proteins, PUM1 and PUM2. (PMID:29165587)
• SAM68 is required for efficient recruitment of PUM2 to NORAD, regulation of Pum activity by NORAD, and proper chromosome segregation in mammalian cells. (PMID:29386330)
• PUM2 suppresses osteosarcoma progression via partly and competitively binding to STARD13 3’UTR with miRNAs (PMID:30084199)
• Using the novel PUM1 and PUM2 mRNA target SIAH1 as a model, this study shows mechanistic differences between PUM1 and PUM2 and between NANOS1, 2, and 3 paralogues in the regulation of SIAH1. (PMID:30269240)
• A transcriptome-wide approach was used to determine the binding profiles and inter-dependencies of Argonaute2 (AGO2), Pumilio (PUM1 and PUM2) sites on mRNA 3’ untranslated regions (3’UTRs). (PMID:30333515)
• A PUM2-mediated layer of post-transcriptional regulation links altered Mff translation to mitochondrial dynamics and mitophagy, thereby mediating age-related mitochondrial dysfunctions. (PMID:30642763)
• PUM2 promote glioblastoma development via repressing BTG1 expression (PMID:30787206)
• circ_0075932 directly bound with the RNA-binding protein PUM2, which was reported to positively regulated AuroraA kinase, thus activating the NF-kappaB pathway. Moreover, either silencing PUM2, silencing AuroraA, or blockade of NF-kappaB activation, could abrogate the promoting effect of adipocyte-derived exosomal circ_0075932 on cell inflammation and apoptosis. (PMID:30824182)
• PUM2 could facilitate the stemness of breast cancer cells by competitively binding to NRP-1 3’UTR with miR-376a. (PMID:30909144)
• PUM2 protein cooperativity mediated by RNA structure has been reported. (PMID:30914482)
• We have used the RNA-MaP platform to directly measure equilibrium binding for thousands of designed RNAs and to construct a predictive model for RNA recognition by the human Pumilio proteins PUM1 and PUM2. (PMID:31078383)
• RNA-binding protein PUM2 regulates mesenchymal stem cell fate via repression of JAK2 and RUNX2 mRNAs. (PMID:31595981)
• LncRNA TUG1 aggravates the progression of cervical cancer by binding PUM2. (PMID:31646551)
• Characterization of RNP Networks of PUM1 and PUM2 Post-Transcriptional Regulators in TCam-2 Cells, a Human Male Germ Cell Model. (PMID:32316190)
• The results suggest that PUM1-2 affects the expression of pluripotency genes as well as the efficiency of the cardiac differentiation process. (PMID:32437472)
• Principles of mRNA control by human PUM proteins elucidated from multimodal experiments and integrative data analysis. (PMID:32753408)
• Human Pumilio proteins directly bind the CCR4-NOT deadenylase complex to regulate the transcriptome. (PMID:33397688)
• CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging. (PMID:33542625)
• RNA-binding protein PUM2 promotes T-cell acute lymphoblastic leukemia via competitively binding to RBM5 3’UTR with miR-28-5p. (PMID:36536516)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pum2	ENSDARG00000061040
mus_musculus	Pum2	ENSMUSG00000020594
rattus_norvegicus	Pum2	ENSRNOG00000006180
drosophila_melanogaster	pum	FBGN0003165
caenorhabditis_elegans		WBGENE00001401
caenorhabditis_elegans		WBGENE00001402
caenorhabditis_elegans		WBGENE00004239
caenorhabditis_elegans		WBGENE00004241
caenorhabditis_elegans		WBGENE00004242
caenorhabditis_elegans		WBGENE00004243
caenorhabditis_elegans		WBGENE00004245
caenorhabditis_elegans		WBGENE00022257

Paralogs (1): PUM1 (ENSG00000134644)

Protein

Protein identifiers

Pumilio homolog 2 — Q8TB72 (reviewed: Q8TB72)

All UniProt accessions (6): A0A0C4DG68, C9JE24, C9JW01, Q8TB72, F2Z366, F8WD57

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3’-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5’-UGUANAUA-3’, that is related to the Nanos Response Element (NRE) (, PubMed:21397187). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Also mediates deadenylation-independent repression by promoting accessibility of miRNAs. Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3’-UTR and facilitating miRNA regulation. Plays a role in cytoplasmic sensing of viral infection. Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm. May regulate DCUN1D3 mRNA levels. May support proliferation and self-renewal of stem cells. Binds specifically to miRNA MIR199A precursor, with PUM1, regulates miRNA MIR199A expression at a postranscriptional level.

Subunit / interactions. Homodimer; homodimerizes in vitro. Interacts with DAZ1, DAZL and NANOS1 via its pumilio repeats. Interacts with NANOS3. Interacts with SNAPIN. Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Interacts with DDX20. In case of viral infection, interacts with DHX58. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner.

Subcellular location. Cytoplasm. Cytoplasmic granule. Perinuclear region.

Tissue specificity. Expressed in male germ cells of adult testis (at protein level). Highly expressed in testis and ovary. Predominantly expressed in stem cells and germ cells. Expressed at lower level in brain, heart, kidney, liver, muscle, placenta, intestine and stomach Expressed in cerebellum, corpus callosum, caudate nucleus, hippocampus, medulla oblongata and putamen. Expressed in all fetal tissues tested.

Domain organisation. The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. PUM2 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine.

Induction. Down-regulated in keratinocytes upon UVB irradiation.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TB72-1	1	yes
Q8TB72-2	2
Q8TB72-3	3
Q8TB72-4	4

RefSeq proteins (15): NP_001269681, NP_001269719, NP_001269720, NP_001339846, NP_001339847, NP_001339848, NP_001339849, NP_001339852, NP_001339854, NP_001339855, NP_001339856, NP_001339857, NP_001339858, NP_001339859, NP_056132* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001313	Pumilio_RNA-bd_rpt	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR033133	PUM-HD	Domain
IPR033712	Pumilio_RNA-bd	Domain

Pfam: PF00806

UniProt features (80 total): helix 31, modified residue 13, region of interest 12, repeat 8, compositionally biased region 5, turn 4, splice variant 3, chain 1, domain 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3Q0Q	X-RAY DIFFRACTION	2
3Q0R	X-RAY DIFFRACTION	2
3Q0S	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB72-F1	56.75	0.33

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 (13): 67, 82, 102, 136, 178, 182, 184, 396, 587, 592, 674, 684, 700

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 403 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MODULE_97, GOBP_EPITHELIUM_DEVELOPMENT, HNF3ALPHA_Q6, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_182, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

GO Biological Process (20): skeletal system development (GO:0001501), hair follicle development (GO:0001942), regulation of translation (GO:0006417), mitochondrion organization (GO:0007005), post-transcriptional regulation of gene expression (GO:0010608), respiratory electron transport chain (GO:0022904), stress granule assembly (GO:0034063), miRNA processing (GO:0035196), regulation of mRNA stability (GO:0043488), positive regulation of sprouting of injured axon (GO:0048687), chromosome organization (GO:0051276), regulation of chromosome segregation (GO:0051983), adipose tissue development (GO:0060612), regulation of miRNA-mediated gene silencing (GO:0060964), 3’-UTR-mediated mRNA destabilization (GO:0061158), regulation of postsynapse assembly (GO:0150052), positive regulation of RIG-I signaling pathway (GO:1900246), regulation of intracellular mRNA localization (GO:1904580), positive regulation of miRNA-mediated gene silencing (GO:2000637), negative regulation of gene expression (GO:0010629)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), miRNA binding (GO:0035198), pumilio-response element binding (GO:0062104), lncRNA binding (GO:0106222), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), nuclear membrane (GO:0031965), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
organelle organization	2
regulation of gene expression	2
miRNA-mediated post-transcriptional gene silencing	2
RNA binding	2
cytoplasm	2
synapse	2
system development	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
electron transport chain	1
cellular respiration	1
membraneless organelle assembly	1
regulatory ncRNA processing	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
positive regulation of axon regeneration	1
sprouting of injured axon	1
regulation of sprouting of injured axon	1
chromosome segregation	1
regulation of cell cycle process	1
animal organ development	1
connective tissue development	1
regulation of post-transcriptional gene silencing by regulatory ncRNA	1
mRNA destabilization	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
RIG-I signaling pathway	1
regulation of RIG-I signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
intracellular mRNA localization	1
regulation of localization	1

Protein interactions and networks

STRING

4568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PUM2	DAZL	Q92904	984
PUM2	NANOS1	Q8WY41	978
PUM2	DAZ1	Q9NQZ3	968
PUM2	MOV10	Q9HCE1	870
PUM2	BOLL	Q8N9W6	862
PUM2	AGO2	Q9UKV8	827
PUM2	CPEB1	Q9BZB8	741
PUM2	FMR1	Q06787	740
PUM2	EIF4ENIF1	Q9NRA8	739
PUM2	EIF4E	P06730	686
PUM2	RBFOX2	O43251	668
PUM2	DDX6	P26196	661
PUM2	AGO1	Q9UL18	650
PUM2	QKI	Q96PU8	640
PUM2	KHDRBS1	Q07666	604

IntAct

80 interactions, top by confidence:

A	B	Type	Score
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ORF	EIF3F	psi-mi:“MI:0914”(association)	0.560
PUM2	ORF	psi-mi:“MI:0915”(physical association)	0.560
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CELF5	CASC3	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
ILF2	RRP8	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ELAVL2	CASC3	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
MCRIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
BOLL	PUM2	psi-mi:“MI:0915”(physical association)	0.510
PUM2	BOLL	psi-mi:“MI:0915”(physical association)	0.510
PUM2	DAZ1	psi-mi:“MI:0915”(physical association)	0.510
DAZ1	PUM2	psi-mi:“MI:0915”(physical association)	0.510
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
PUM2	PUM2	psi-mi:“MI:0915”(physical association)	0.400
DAZL	PUM2	psi-mi:“MI:0915”(physical association)	0.370
MED23	PUM2	psi-mi:“MI:0915”(physical association)	0.370
SAMD1		psi-mi:“MI:0914”(association)	0.350
RBM45	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
DICER1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (202): NANOS3 (Affinity Capture-Western), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS), PUM2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5R1, A2YXQ1, A4F5G6, A6NFN3, A6QPR6, E3WDQ9, O42366, O43251, O65034, O80416, P24344, P35453, P46609, P55316, P56260, P70217, Q00939, Q02962, Q0VD23, Q14671, Q17QD3, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q1KKX5, Q27002, Q2VB19, Q5NVN8, Q5R5X3, Q60987, Q642J5, Q66JB7, Q66KI6, Q6YHU8, Q6ZBH6, Q6ZK57, Q7TN99

Diamond homologs: E3WDQ9, O74438, O94462, P25822, Q07807, Q10238, Q14671, Q2VB19, Q5R5X3, Q66KI6, Q80U58, Q80U78, Q8TB72, Q9C5E7, Q9LJX4, Q9SS47, Q9ZW02, Q9ZW06, Q9ZW07, P39016, Q09829, Q1PFN9, Q9C9R6, Q9LM20, Q9LVC3, P25339, Q92359, Q9LDW3, Q9LP21, Q9P789, O60059, Q9XI17, Q9FIE9, Q9LSS8, Q9LVG3, Q9C8B8, Q9LNI2, Q9LXC5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“CCR4-NOT complex”	“down-regulates quantity by repression”	PUM2	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
3’-UTR-mediated mRNA stabilization	6	51.4×	6e-07
RNA splicing	7	7.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3700 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20251712:CGAAT:C	acceptor_gain	1.0000
2:20251713:GAAT:G	acceptor_gain	1.0000
2:20251715:AT:A	acceptor_gain	1.0000
2:20251716:TCTG:T	acceptor_loss	1.0000
2:20251717:C:CC	acceptor_gain	1.0000
2:20251717:CTG:C	acceptor_loss	1.0000
2:20253818:TTA:T	donor_loss	1.0000
2:20254010:CATTG:C	acceptor_gain	1.0000
2:20254011:ATTG:A	acceptor_gain	1.0000
2:20254012:TTG:T	acceptor_gain	1.0000
2:20254013:TG:T	acceptor_gain	1.0000
2:20254015:C:CC	acceptor_gain	1.0000
2:20254021:A:AC	acceptor_gain	1.0000
2:20254022:T:C	acceptor_gain	1.0000
2:20254022:T:TC	acceptor_gain	1.0000
2:20254858:AATAC:A	donor_loss	1.0000
2:20254859:ATAC:A	donor_loss	1.0000
2:20254860:TA:T	donor_loss	1.0000
2:20254861:ACC:A	donor_loss	1.0000
2:20254862:C:CT	donor_loss	1.0000
2:20254984:CCTAA:C	acceptor_loss	1.0000
2:20254985:C:CC	acceptor_gain	1.0000
2:20254985:CTAAG:C	acceptor_loss	1.0000
2:20254986:T:C	acceptor_loss	1.0000
2:20255212:ATACC:A	donor_loss	1.0000
2:20255215:C:CT	donor_loss	1.0000
2:20255221:CCAA:C	donor_gain	1.0000
2:20255224:A:AC	donor_gain	1.0000
2:20255225:C:CC	donor_gain	1.0000
2:20255225:CTG:C	donor_gain	1.0000

AlphaMissense

6546 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000019338 (2:20286051 ACAAGGGG>A), RS1000039942 (2:20264919 T>A), RS1000072350 (2:20264716 T>C), RS1000099109 (2:20313033 C>T), RS1000106471 (2:20271582 G>A), RS1000123418 (2:20350972 G>A,T), RS1000139179 (2:20294807 G>A,C), RS1000185057 (2:20324528 C>G), RS1000187542 (2:20283857 G>A), RS1000188033 (2:20250613 A>T), RS1000237159 (2:20324198 A>C), RS1000241569 (2:20253512 CTTTTTTT>C,CTTT,CTTTT,CTTTTT,CTTTTTT,CTTTTTTTT,CTTTTTTTTT), RS1000252588 (2:20289911 G>A), RS1000351766 (2:20339542 A>G), RS1000363842 (2:20259880 T>C)

Disease associations

OMIM: gene MIM:607205 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004904_124	Body mass index	2.000000e-08
GCST010204_44	Low density lipoprotein cholesterol levels	1.000000e-306
GCST010241_329	Apolipoprotein A1 levels	3.000000e-08
GCST010243_78	Apolipoprotein B levels	7.000000e-11
GCST90000025_796	Appendicular lean mass	5.000000e-18

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067206 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.48	Kd	332.2	nM	CHEMBL3752910
6.28	ED50	526.1	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149921: Binding affinity to human PUM2 incubated for 45 mins by Kinobead based pull down assay	kd	0.3322	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Doxorubicin	decreases reaction, increases expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
coumarin	increases phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
nutlin 3	affects cotreatment, increases secretion	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Aspirin	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652963	Binding	Binding affinity to human PUM2 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)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder