PUM1

Summary

PUM1 (pumilio RNA binding family member 1, HGNC:14957) is a protein-coding gene on chromosome 1p35.2, encoding Pumilio homolog 1 (Q14671). Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3’-UTR of mRNA targets. It is a selective cancer dependency (DepMap: 10.7% of cell lines).

This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3’ untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 9698 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 368 total — 11 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 53
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.7% of screened cell lines
• MANE Select transcript: NM_001020658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14957
Approved symbol	PUM1
Name	pumilio RNA binding family member 1
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	PUMH1, KIAA0099
Ensembl gene	ENSG00000134644
Ensembl biotype	protein_coding
OMIM	607204
Entrez	9698

Gene structure

Transcript identifiers

Ensembl transcripts: 226 — 216 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000257075, ENST00000373741, ENST00000373742, ENST00000373747, ENST00000424085, ENST00000426105, ENST00000440538, ENST00000471894, ENST00000480602, ENST00000490546, ENST00000498419, ENST00000498627, ENST00000524516, ENST00000525843, ENST00000525948, ENST00000525997, ENST00000526128, ENST00000526215, ENST00000527498, ENST00000529846, ENST00000530669, ENST00000531867, ENST00000532678, ENST00000883066, ENST00000883067, ENST00000883068, ENST00000883069, ENST00000883070, ENST00000883071, ENST00000883072, ENST00000883073, ENST00000883074, ENST00000883075, ENST00000883076, ENST00000883077, ENST00000883078, ENST00000883079, ENST00000883080, ENST00000883081, ENST00000883082, ENST00000883083, ENST00000883084, ENST00000883085, ENST00000883086, ENST00000883087, ENST00000883088, ENST00000883089, ENST00000883090, ENST00000883091, ENST00000883092, ENST00000883093, ENST00000883094, ENST00000883095, ENST00000883096, ENST00000883097, ENST00000883098, ENST00000883099, ENST00000883100, ENST00000883101, ENST00000883102, ENST00000883103, ENST00000883104, ENST00000883105, ENST00000883106, ENST00000883107, ENST00000883108, ENST00000883109, ENST00000883110, ENST00000883111, ENST00000883112, ENST00000883113, ENST00000883114, ENST00000883115, ENST00000883116, ENST00000883117, ENST00000883118, ENST00000883119, ENST00000883120, ENST00000883121, ENST00000883122, ENST00000883123, ENST00000883124, ENST00000883125, ENST00000883126, ENST00000883127, ENST00000883128, ENST00000883129, ENST00000883130, ENST00000883131, ENST00000883132, ENST00000883133, ENST00000883134, ENST00000883135, ENST00000883136, ENST00000883137, ENST00000883138, ENST00000883139, ENST00000883140, ENST00000883141, ENST00000883142, ENST00000883143, ENST00000883144, ENST00000883145, ENST00000883146, ENST00000883147, ENST00000883148, ENST00000883149, ENST00000883150, ENST00000883151, ENST00000883152, ENST00000883153, ENST00000883154, ENST00000883155, ENST00000883156, ENST00000883157, ENST00000883158, ENST00000883159, ENST00000883160, ENST00000883161, ENST00000883162, ENST00000883163, ENST00000883164, ENST00000883165, ENST00000883166, ENST00000883167, ENST00000883168, ENST00000883169, ENST00000883170, ENST00000883171, ENST00000883172, ENST00000883173, ENST00000883174, ENST00000883175, ENST00000883176, ENST00000883177, ENST00000883178, ENST00000883179, ENST00000883180, ENST00000918937, ENST00000918938, ENST00000918939, ENST00000918940, ENST00000918941, ENST00000918942, ENST00000918943, ENST00000918944, ENST00000918945, ENST00000918946, ENST00000918947, ENST00000918948, ENST00000918949, ENST00000918950, ENST00000918951, ENST00000918952, ENST00000918953, ENST00000918954, ENST00000918955, ENST00000918956, ENST00000918957, ENST00000918958, ENST00000918959, ENST00000918960, ENST00000918961, ENST00000918962, ENST00000918963, ENST00000918964, ENST00000918965, ENST00000918966, ENST00000918967, ENST00000918968, ENST00000918969, ENST00000918970, ENST00000918971, ENST00000918972, ENST00000918973, ENST00000918974, ENST00000918975, ENST00000918976, ENST00000918977, ENST00000918978, ENST00000918979, ENST00000918980, ENST00000918981, ENST00000918982, ENST00000918983, ENST00000918984, ENST00000963524, ENST00000963525, ENST00000963526, ENST00000963527, ENST00000963528, ENST00000963529, ENST00000963530, ENST00000963531, ENST00000963532, ENST00000963533, ENST00000963534, ENST00000963535, ENST00000963536, ENST00000963537, ENST00000963538, ENST00000963539, ENST00000963540, ENST00000963541, ENST00000963542, ENST00000963543, ENST00000963544, ENST00000963545, ENST00000963546, ENST00000963547, ENST00000963548, ENST00000963549, ENST00000963550, ENST00000963551, ENST00000963552, ENST00000963553, ENST00000963554, ENST00000963555, ENST00000963556, ENST00000963557, ENST00000963558, ENST00000963559, ENST00000963560, ENST00000963561, ENST00000963562, ENST00000963563

RefSeq mRNA: 2 — MANE Select: NM_001020658 NM_001020658, NM_014676

CCDS: CCDS338, CCDS44099

Canonical transcript exons

ENST00000426105 — 22 exons

Exon	Start	End
ENSE00000916508	30941998	30942123
ENSE00000916510	30945346	30945483
ENSE00000916513	30953714	30953981
ENSE00000916514	30964674	30964910
ENSE00000916515	30965982	30966278
ENSE00000916522	30992390	30992660
ENSE00001065956	30931506	30933342
ENSE00003481617	30941151	30941272
ENSE00003503735	30950127	30950261
ENSE00003519177	31005853	31006031
ENSE00003552709	30968354	30968492
ENSE00003576928	31028796	31028864
ENSE00003586789	30974651	30974802
ENSE00003607854	31059204	31059577
ENSE00003614192	30967167	30967310
ENSE00003624102	30952234	30952363
ENSE00003647362	30981312	30981405
ENSE00003656099	30980062	30980163
ENSE00003671700	30936643	30936835
ENSE00003672677	31006994	31007102
ENSE00003686817	30995054	30995220
ENSE00003899818	31065616	31065717

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5937 / max 574.1446, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11449	27.2021	1816
11446	0.3916	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.89	gold quality
CA1 field of hippocampus	UBERON:0003881	98.88	gold quality
germinal epithelium of ovary	UBERON:0001304	98.80	gold quality
superficial temporal artery	UBERON:0001614	98.70	gold quality
visceral pleura	UBERON:0002401	98.65	gold quality
tibia	UBERON:0000979	98.60	gold quality
gingival epithelium	UBERON:0001949	98.59	gold quality
hair follicle	UBERON:0002073	98.59	gold quality
inferior olivary complex	UBERON:0002127	98.59	gold quality
parietal pleura	UBERON:0002400	98.54	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.54	gold quality
pleura	UBERON:0000977	98.51	gold quality
middle temporal gyrus	UBERON:0002771	98.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.47	gold quality
gluteal muscle	UBERON:0002000	98.39	gold quality
cervix squamous epithelium	UBERON:0006922	98.38	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.31	gold quality
seminal vesicle	UBERON:0000998	98.29	gold quality
caput epididymis	UBERON:0004358	98.27	gold quality
gingiva	UBERON:0001828	98.23	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.23	gold quality
substantia nigra pars compacta	UBERON:0001965	98.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.20	gold quality
adult organism	UBERON:0007023	98.16	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.12	gold quality
epithelium of nasopharynx	UBERON:0001951	98.07	gold quality
postcentral gyrus	UBERON:0002581	98.06	gold quality
nasopharynx	UBERON:0001728	98.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.05	gold quality
palpebral conjunctiva	UBERON:0001812	98.03	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.67
E-ENAD-17	no	2752.08
E-MTAB-6386	no	473.51
E-GEOD-124858	no	258.10
E-MTAB-6524	no	119.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting PUM1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• The reference genes of choice when performing RT-qPCR on normal and malignant breast specimens should be either the collected group of 3 genes (TBP, RPLP0 and PUM1) employed as an average, or PUM1 as a single gene. (PMID:18211679)
• Description of the structures of hPum Puf domain complexed to two noncognate RNAs, CycB(reverse) and Puf5. (PMID:18328718)
• ribonomic analysis of mRNAs associated with ribonucleoproteins containing an endogenous human PUF protein, Pum1 (PMID:18411299)
• Puf-A transcripts were uniformly distributed in early embryos, but became restricted primarily to eyes and ovaries at a later stage of development (PMID:19319195)
• Pumilio-1 (PUM1) is a ubiquitously expressed RBP that was shown to interact with p27-3’ UTR. (PMID:20818387)
• Three distinct modes of target RNA binding by PUM1 around the fifth mRNA base were observed. (PMID:21397187)
• 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)
• MED15 and PUM1 proteins with coiled-coil domains are potent enhancers of polyQ-mediated ataxin-1 protein misfolding and proteotoxicity in vitro and in vivo. (PMID:22916034)
• The promoting effect of hPuf-A in tumorigenesis might be correlated with the regulation of its associated mRNAs. (PMID:23625657)
• PUM repeats have now been identified in proteins that function in pre-rRNA processing, including human Puf-A and yeast Puf6. (PMID:25512524)
• 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)
• 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)
• Results indicate that pumilio RNA binding family member 1 (PUM1) is a negative regulator of RNA helicase LGP2 (LGP2), a master regulator of innate immunity genes expressed in a cascade fashion. (PMID:28760986)
• PUM1 SNP is associated with Osteoporosis and Obesity. (PMID:29145611)
• Data indicate that RNAs-including mRNAs and non-coding RNAs-that are functionally regulated by Pumilio proteins, PUM1 and PUM2. (PMID:29165587)
• Variants in PUM1 may not contribute to primary ovarian insufficiency in Han Chinese women (PMID:29297114)
• the extent of Pumilio binding to the endogenous RGC-32 mRNA in EBV-infected cell lines also correlated with RGC-32 protein expression. Our data demonstrate the importance of RGC-32 for the survival of EBV-immortalised B cells and identify Pumilio as a key regulator of RGC-32 translation. (PMID:29385536)
• Thus, PUM1 promotes the development and progression of ovarian cancer, which may occur via the above-mentioned molecules. (PMID:29428722)
• Studies in patient-derived cells revealed that the missense mutations reduced PUM1 protein levels by approximately 25% in the adult-onset cases and by approximately 50% in the infantile-onset cases; levels of known PUM1 targets increased accordingly. (PMID:29474920)
• 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)
• 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)
• PUM binding is required for maintenance of genomic stability by NORAD whereas binding of RBMX is dispensable for this function. (PMID:31343408)
• our results revealed that PUM1 knockdown suppressed cell growth, invasion, and metastasis, and promoted apoptosis by activating the PERK/eIF2/ATF4 signaling pathway in Pancreatic ductal adenocarcinoma (PDAC) cells. PUM1 could be a potential target to develop pharmaceuticals and novel therapeutic strategies for the treatment of PDAC. (PMID:31395860)
• Investigating PUM1 mutations in a Taiwanese cohort with cerebellar ataxia. (PMID:31422002)
• Characterization of RNP Networks of PUM1 and PUM2 Post-Transcriptional Regulators in TCam-2 Cells, a Human Male Germ Cell Model. (PMID:32316190)
• Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis. (PMID:32375027)
• 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)
• RNA binding protein PUM1 promotes colon cancer cell proliferation and migration. (PMID:33508364)
• PUM1 and RNase P genes as potential cell-free DNA markers in breast cancer. (PMID:33522650)
• NORAD-induced Pumilio phase separation is required for genome stability. (PMID:34108682)
• Identification of Novel Endogenous Controls for qPCR Normalization in SK-BR-3 Breast Cancer Cell Line. (PMID:34681026)
• Novel regulators of PrPC biosynthesis revealed by genome-wide RNA interference. (PMID:34705895)
• PUM1 modulates trophoblast cell proliferation and migration through LRP6. (PMID:34734756)
• TLR4 downregulation by the RNA-binding protein PUM1 alleviates cellular aging and osteoarthritis. (PMID:35034101)
• PUMILIO-mediated translational control of somatic cell cycle program promotes folliculogenesis and contributes to ovarian cancer progression. (PMID:35507203)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pum1	ENSDARG00000099256
mus_musculus	Pum1	ENSMUSG00000028580
rattus_norvegicus	Pum1	ENSRNOG00000011709
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): PUM2 (ENSG00000055917)

Protein

Protein identifiers

Pumilio homolog 1 — Q14671 (reviewed: Q14671)

All UniProt accessions (14): E9PL65, E9PM68, E9PMX1, E9PR38, Q14671, H0YC97, H0YCK1, H0YDC5, H0YDK8, H0YDQ6, H0YED4, H0YEH2, Q5T1Z4, Q5T1Z8

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). 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. Following growth factor stimulation, phosphorylated and binds to the 3’-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle. Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3’-UTR and facilitating miRNA regulation. 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. Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3’-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery. Plays a role in cytoplasmic sensing of viral infection. In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3’-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation. Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level.

Subunit / interactions. Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. In case of viral infection, interacts with DHX58. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner.

Subcellular location. Cytoplasm. P-body. Cytoplasmic granule.

Tissue specificity. Expressed in brain, heart, kidney, muscle, intestine and stomach. Not expressed in cerebellum, corpus callosum, caudate nucleus, hippocampus, medulla oblongata and putamen. Expressed in all fetal tissues tested.

Post-translational modifications. Phosphorylation at Ser-714 promotes RNA-binding activity. Following growth factor stimulation phosphorylated at Ser-714, promoting binding to the 3’-UTR of CDKN1B/p27 mRNA.

Disease relevance. Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism (NEDMSF) [MIM:620719] An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, early-onset seizures, poor overall growth, delayed walking, hypotonia and/or ataxia, and facial dysmorphism. Some patients have hypoplasia of the corpus callosum and cerebral atrophy. The disease is caused by variants affecting the gene represented in this entry.

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. PUM1 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. Strongly down-regulated in keratinocytes upon UVB irradiation.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14671-1	1	yes
Q14671-2	2
Q14671-3	3
Q14671-4	4

RefSeq proteins (2): NP_001018494, NP_055491 (=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 (115 total): helix 33, modified residue 18, mutagenesis site 15, region of interest 13, repeat 8, compositionally biased region 6, splice variant 5, turn 4, sequence variant 4, strand 3, sequence conflict 3, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
1IB2	X-RAY DIFFRACTION	1.9
1M8Z	X-RAY DIFFRACTION	1.9
1M8W	X-RAY DIFFRACTION	2.2
1M8X	X-RAY DIFFRACTION	2.2
5YKI	X-RAY DIFFRACTION	2.25
3BSX	X-RAY DIFFRACTION	2.32
3Q0N	X-RAY DIFFRACTION	2.4
5YKH	X-RAY DIFFRACTION	2.46
3Q0L	X-RAY DIFFRACTION	2.5
2YJY	X-RAY DIFFRACTION	2.6
1M8Y	X-RAY DIFFRACTION	2.6
3Q0P	X-RAY DIFFRACTION	2.6
3Q0M	X-RAY DIFFRACTION	2.71
3BSB	X-RAY DIFFRACTION	2.8
3Q0O	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14671-F1	54.09	0.30

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 (18): 2, 19, 75, 98, 106, 112, 124, 159, 197, 209, 229, 305, 514, 709, 714, 796, 806, 822

Mutagenesis-validated functional residues (15):

Position	Phenotype
209	does not affect rna-binding activity.
714	decreased rna-binding activity.
714	phospho-mimic mutant; persistent rna-binding activity in quiescent cells.
863–867	b and inds cytosine-nucleotide in rna target.
899–903	specifically binds cytosine-nucleotide in rna target.
935–939	specifically binds cytosine-nucleotide in rna target.
971–975	specifically binds cytosine-nucleotide in rna target.
1007–1011	specifically binds cytosine-nucleotide in rna target.
1007–1011	specifically binds guanine-nucleotide in rna target.
1007	specifically binds uracil-nucleotide in rna target.
1043–1047	specifically binds cytosine-nucleotide in rna target.
1043–1044	changes the specificity for rna; when associated with e-1047.
1047	changes the specificity for rna; when associated with 1043-sn-1044.
1079–1083	specifically binds cytosine-nucleotide in rna target.
1122–1126	specifically binds cytosine-nucleotide in rna target.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis

MSigDB gene sets: 404 (showing top): GOBP_BEHAVIOR, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TTTGTAG_MIR520D, GOBP_ADULT_BEHAVIOR, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, YY1_Q6, GGCNKCCATNK_UNKNOWN, GOBP_TRANSLATION, MORF_TERF1, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (16): regulation of translation (GO:0006417), spermatogenesis (GO:0007283), adult locomotory behavior (GO:0008344), post-transcriptional regulation of gene expression (GO:0010608), post-transcriptional gene silencing (GO:0016441), miRNA processing (GO:0035196), regulation of mRNA stability (GO:0043488), stem cell differentiation (GO:0048863), regulation of cell cycle (GO:0051726), regulation of chromosome segregation (GO:0051983), regulation of miRNA-mediated gene silencing (GO:0060964), mRNA destabilization (GO:0061157), 3’-UTR-mediated mRNA destabilization (GO:0061158), positive regulation of RIG-I signaling pathway (GO:1900246), positive regulation of miRNA-mediated gene silencing (GO:2000637), cell differentiation (GO:0030154)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), miRNA binding (GO:0035198), protein binding (GO:0005515)

GO Cellular Component (6): P-body (GO:0000932), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), axon (GO:0030424)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
post-transcriptional regulation of gene expression	2
negative regulation of gene expression	2
miRNA-mediated post-transcriptional gene silencing	2
cytoplasmic ribonucleoprotein granule	2
translation	1
regulation of protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
locomotory behavior	1
adult behavior	1
regulation of gene expression	1
regulatory ncRNA processing	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
cell differentiation	1
cell cycle	1
regulation of cellular process	1
chromosome segregation	1
regulation of cell cycle process	1
regulation of post-transcriptional gene silencing by regulatory ncRNA	1
regulation of mRNA stability	1
RNA destabilization	1
positive regulation of mRNA catabolic process	1
mRNA destabilization	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
regulation of miRNA-mediated gene silencing	1
positive regulation of post-transcriptional gene silencing by RNA	1
cellular developmental process	1
nucleic acid binding	1
mRNA binding	1
regulatory RNA binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
neuron projection	1

Protein interactions and networks

STRING

5276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PUM1	DAZL	Q92904	723
PUM1	RBFOX2	O43251	712
PUM1	DAZ1	Q9NQZ3	657
PUM1	CNOT7	Q9UIV1	633
PUM1	RBFOX3	A6NFN3	632
PUM1	MRPL19	P49406	602
PUM1	PSMC4	P43686	577
PUM1	CNOT8	Q9UFF9	571
PUM1	E2F3	O00716	570
PUM1	CDKN1B	P46527	554
PUM1	IPO8	O15397	525
PUM1	PUM3	Q15397	515
PUM1	KHSRP	Q92945	515
PUM1	AAMP	Q13685	509
PUM1	AGO2	Q9UKV8	494
PUM1	DDX6	P26196	494

IntAct

170 interactions, top by confidence:

A	B	Type	Score
CLOCK	BMAL1	psi-mi:“MI:0914”(association)	0.880
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
GPR37	PUM1	psi-mi:“MI:0915”(physical association)	0.560
GRN	PUM1	psi-mi:“MI:0915”(physical association)	0.560
PUM1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PUM1	YWHAE	psi-mi:“MI:0915”(physical association)	0.540
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530

BioGRID (380): PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), SEPHS1 (Co-fractionation), PUM1 (Affinity Capture-MS), PUM1 (Proximity Label-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (Affinity Capture-MS), PUM1 (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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“CCR4-NOT complex”	“down-regulates quantity by repression”	PUM1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	54.9×	3e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	48.5×	5e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	48.5×	5e-09
Activation of BH3-only proteins	7	35.8×	5e-08
RHO GTPases activate PKNs	7	22.9×	1e-06
Intrinsic Pathway for Apoptosis	7	21.1×	2e-06
FOXO-mediated transcription	5	17.3×	3e-04
SARS-CoV-1-host interactions	9	16.3×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transport	7	14.2×	3e-04
protein targeting	5	14.1×	9e-03
intracellular protein localization	12	9.7×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	12
Uncertain significance	239
Likely benign	42
Benign	27

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1012521	NM_001020658.2(PUM1):c.2352C>G (p.Tyr784Ter)	Pathogenic
1031839	NM_001020658.2(PUM1):c.3028C>T (p.Arg1010Ter)	Pathogenic
1698881	NM_001020658.2(PUM1):c.213dup (p.Ala72fs)	Pathogenic
2363668	NM_001020658.2(PUM1):c.962_965dup (p.Ala323fs)	Pathogenic
3149783	NM_001020658.2(PUM1):c.2500G>T (p.Glu834Ter)	Pathogenic
3384363	NM_001020658.2(PUM1):c.3202C>T (p.Arg1068Ter)	Pathogenic
3777062	NM_001020658.2(PUM1):c.1159del (p.Leu387fs)	Pathogenic
3941069	NM_001020658.2(PUM1):c.2452C>T (p.Arg818Ter)	Pathogenic
4072486	NM_001020658.2(PUM1):c.517C>T (p.Arg173Ter)	Pathogenic
4680887	NM_001020658.2(PUM1):c.2764C>T (p.Arg922Ter)	Pathogenic
4796711	GRCh38/hg38 1p35.2(chr1:30936422-30948423)x3	Pathogenic
1027534	NM_001020658.2(PUM1):c.221G>A (p.Arg74His)	Likely pathogenic
1700117	NM_001020658.2(PUM1):c.523_527del (p.Ser175fs)	Likely pathogenic
2576120	NM_001020658.2(PUM1):c.1738C>T (p.Arg580Ter)	Likely pathogenic
2682270	NM_001020658.2(PUM1):c.1876C>T (p.Gln626Ter)	Likely pathogenic
3600359	NM_001020658.2(PUM1):c.2264_2291dup (p.Ser765fs)	Likely pathogenic
3776035	NM_001020658.2(PUM1):c.364-2A>G	Likely pathogenic
4813063	NM_001020658.2(PUM1):c.1544dup (p.Asn516fs)	Likely pathogenic
4820071	NM_001020658.2(PUM1):c.631C>T (p.Arg211Ter)	Likely pathogenic
617929	NM_001020658.2(PUM1):c.3415C>T (p.Arg1139Trp)	Likely pathogenic
916512	NM_001020658.2(PUM1):c.2518C>T (p.Arg840Trp)	Likely pathogenic
929062	NM_001020658.2(PUM1):c.1773del (p.Ser592fs)	Likely pathogenic
984948	NM_001020658.2(PUM1):c.46G>T (p.Asp16Tyr)	Likely pathogenic

SpliceAI

4284 predictions. Top by Δscore:

Variant	Effect	Δscore
1:30933339:GGATC:G	acceptor_loss	1.0000
1:30933340:GATC:G	acceptor_loss	1.0000
1:30933343:CTGGG:C	acceptor_loss	1.0000
1:30933344:T:G	acceptor_loss	1.0000
1:30936638:CCTA:C	donor_loss	1.0000
1:30936639:CTA:C	donor_loss	1.0000
1:30936640:TA:T	donor_loss	1.0000
1:30936641:A:AC	donor_gain	1.0000
1:30936642:C:CC	donor_gain	1.0000
1:30936642:C:CT	donor_loss	1.0000
1:30936831:CATTG:C	acceptor_gain	1.0000
1:30936832:ATTG:A	acceptor_gain	1.0000
1:30936833:TTG:T	acceptor_gain	1.0000
1:30936834:TG:T	acceptor_gain	1.0000
1:30936834:TGC:T	acceptor_loss	1.0000
1:30936835:GC:G	acceptor_loss	1.0000
1:30936836:C:CC	acceptor_gain	1.0000
1:30936836:CT:C	acceptor_loss	1.0000
1:30936837:T:A	acceptor_loss	1.0000
1:30936838:G:C	acceptor_gain	1.0000
1:30941147:GTAC:G	donor_loss	1.0000
1:30941149:A:AC	donor_gain	1.0000
1:30941150:C:CC	donor_gain	1.0000
1:30941150:CCTTG:C	donor_gain	1.0000
1:30941268:TGATC:T	acceptor_gain	1.0000
1:30941269:GATC:G	acceptor_gain	1.0000
1:30941270:ATC:A	acceptor_gain	1.0000
1:30941270:ATCC:A	acceptor_loss	1.0000
1:30941271:TC:T	acceptor_gain	1.0000
1:30941271:TCC:T	acceptor_loss	1.0000

AlphaMissense

7768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:30933281:A:G	L1164P	1.000
1:30933283:C:A	K1163N	1.000
1:30933283:C:G	K1163N	1.000
1:30933285:T:C	K1163E	1.000
1:30933290:A:G	L1161P	1.000
1:30933293:A:C	I1160S	1.000
1:30933293:A:G	I1160T	1.000
1:30933293:A:T	I1160N	1.000
1:30933295:G:C	H1159Q	1.000
1:30933295:G:T	H1159Q	1.000
1:30933296:T:C	H1159R	1.000
1:30933297:G:C	H1159D	1.000
1:30933297:G:T	H1159N	1.000
1:30933298:C:A	K1158N	1.000
1:30933298:C:G	K1158N	1.000
1:30933299:T:A	K1158M	1.000
1:30933300:T:C	K1158E	1.000
1:30933302:C:A	G1157V	1.000
1:30933302:C:T	G1157D	1.000
1:30933303:C:A	G1157C	1.000
1:30933303:C:G	G1157R	1.000
1:30933303:C:T	G1157S	1.000
1:30933306:A:C	Y1156D	1.000
1:30933306:A:G	Y1156H	1.000
1:30933317:C:G	R1152P	1.000
1:30933320:A:C	L1151R	1.000
1:30933320:A:G	L1151P	1.000
1:30933320:A:T	L1151H	1.000
1:30933341:A:C	I1144S	1.000
1:30933341:A:G	I1144T	1.000

dbSNP variants (sampled 300 via entrez): RS1000013752 (1:31001417 T>C), RS1000030164 (1:30958761 C>A), RS1000038907 (1:30968909 A>G), RS1000057345 (1:31058070 G>A,C), RS1000061281 (1:30964573 A>G), RS1000066779 (1:31046327 G>A,C,T), RS1000118219 (1:31051865 G>A), RS1000129339 (1:31042358 C>T), RS1000185406 (1:31048810 A>G), RS1000192182 (1:30946019 A>C), RS1000194538 (1:30932279 T>C), RS1000295801 (1:30995923 T>G), RS1000331050 (1:30971315 T>C), RS1000379248 (1:31023870 A>C), RS1000381823 (1:31030196 G>A)

Disease associations

OMIM: gene MIM:607204 | disease phenotypes: MIM:617931, MIM:108600, MIM:620719

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism	Strong	Autosomal dominant
spinocerebellar ataxia 47	Moderate	Autosomal dominant

Mondo (6): spinocerebellar ataxia 47 (MONDO:0033482), spastic ataxia (MONDO:0017845), neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism (MONDO:0958231), intellectual disability (MONDO:0001071), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (5): PUM1-related cerebellar ataxia (Orphanet:642747), Spastic ataxia (Orphanet:316226), PUM1-associated developmental disability-ataxia-seizure syndrome (Orphanet:589515), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000508	Ptosis
HP:0000653	Sparse eyelashes
HP:0000677	Oligodontia
HP:0000767	Pectus excavatum
HP:0001007	Hirsutism
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001382	Joint hypermobility
HP:0001511	Intrauterine growth retardation
HP:0001770	Toe syndactyly
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90020026_534	Hip index	4.000000e-08
GCST90020026_535	Hip index	4.000000e-21
GCST90020028_523	Hip circumference adjusted for BMI	1.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067257 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, increases methylation, affects cotreatment	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
sodium arsenite	affects binding, increases reaction	1
coumarin	increases phosphorylation	1
tamibarotene	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	decreases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	affects expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Tretinoin	decreases expression	1
Uranium	affects expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases 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
CHEMBL5652196	Binding	Binding affinity to human PUM1 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2CV	Abcam HeLa PUM1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
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