PUM1

pumilio RNA binding family member 1, the group of Small nucleolar RNA protein coding host genes|Pumilio homology domain containing

Basic information

Region (hg38): 1:30931506-31065991

Links

ENSG00000134644 ∙ NCBI:9698 ∙ OMIM:607204 ∙ HGNC:14957 ∙ Uniprot:Q14671 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia 47 (Limited), mode of inheritance: AD
• spinocerebellar ataxia 47 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 47; Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	29474920; 30903679; 31859446; 35386260

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PUM1 gene.

• Spinocerebellar ataxia 47 (2 variants)
• Inborn genetic diseases (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	18	4	23
missense		6	94	4	2	106
nonsense	3	2	2			7
start loss						0
frameshift	2	2	1			5
inframe indel			4			4
splice donor/acceptor (+/-2bp)			1			1
splice region			5	2	2	9
non coding				2	23	25
Total	5	10	103	24	29

Variants in PUM1

This is a list of pathogenic ClinVar variants found in the PUM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-30933228-G-T			Uncertain significance (Jul 02, 2019)
1-30933230-G-A			Uncertain significance (Mar 10, 2023)
1-30933309-T-C			Uncertain significance (Jan 11, 2022)
1-30933339-G-A		Spinocerebellar ataxia 47 • Inborn genetic diseases • Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism	Pathogenic/Likely pathogenic (Apr 29, 2024)
1-30936656-A-G			Uncertain significance (Jan 30, 2023)
1-30936663-G-A		SPINOCEREBELLAR ATAXIA 47, EARLY-ONSET • Spinocerebellar ataxia 47	Likely pathogenic (Oct 15, 2018)
1-30936713-T-A			Uncertain significance (Jun 15, 2023)
1-30936729-T-A			Uncertain significance (Dec 04, 2023)
1-30936735-A-G			Uncertain significance (Jan 22, 2024)
1-30936753-C-T			Uncertain significance (Sep 26, 2022)
1-30936777-C-T		PUM1-related disorder	Uncertain significance (Sep 07, 2023)
1-30936787-A-G		PUM1-related disorder	Likely benign (Jul 01, 2024)
1-30936792-G-A			Uncertain significance (Jan 05, 2022)
1-30936795-C-T		Spinocerebellar ataxia 47	Uncertain significance (Apr 03, 2020)
1-30936796-C-T		PUM1-related disorder	Likely benign (Apr 13, 2022)
1-30936801-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
1-30936807-CGTGA-C		Neurodevelopmental disorder	Uncertain significance (Jan 01, 2022)
1-30936879-CCT-C		Spinocerebellar ataxia 47	Benign (Nov 07, 2021)
1-30941125-T-C			Benign (May 17, 2021)
1-30941173-A-G		PUM1-related disorder	Likely benign (Apr 25, 2019)
1-30941184-T-C			Uncertain significance (Oct 15, 2023)
1-30941226-C-T		Inborn genetic diseases	Uncertain significance (May 15, 2023)
1-30941279-G-C			Uncertain significance (Nov 25, 2019)
1-30941990-T-A		PUM1-related disorder	Benign (Mar 04, 2019)
1-30941991-C-A		PUM1-related disorder	Benign (Mar 04, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PUM1	protein_coding	protein_coding	ENST00000426105	21	134486

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.47e-8	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.42	361	687	0.525	0.0000389	7728
Missense in Polyphen		69	212.92	0.32406		2412
Synonymous	0.424	257	266	0.967	0.0000164	2401
Loss of Function	6.82	3	60.0	0.0500	0.00000325	645

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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:21572425, PubMed:18328718, PubMed:21653694, 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 (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). 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 (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). 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 (PubMed:26724866). 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 (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). 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 (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000250|UniProtKB:Q80U78, ECO:0000269|PubMed:18328718, ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:20818387, ECO:0000269|PubMed:20860814, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:21572425, ECO:0000269|PubMed:21653694, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25768905, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:29474920}.
• Disease: DISEASE: Spinocerebellar ataxia 47 (SCA47) [MIM:617931]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA47 is an autosomal dominant disease with a highly variable phenotype and incomplete penetrance. Clinical features include developmental disability, ataxia, and seizures. {ECO:0000269|PubMed:29474920}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking (Consensus)

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.229
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.1

Haploinsufficiency Scores

• pHI: 0.362
• hipred: Y
• hipred_score: 0.662
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pum1
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: spermatogenesis;adult locomotory behavior;posttranscriptional regulation of gene expression;posttranscriptional gene silencing;production of miRNAs involved in gene silencing by miRNA;regulation of mRNA stability;stem cell differentiation;regulation of cell cycle;regulation of chromosome segregation;regulation of gene silencing by miRNA;mRNA destabilization;positive regulation of RIG-I signaling pathway;positive regulation of gene silencing by miRNA
• Cellular component: P-body;nucleus;nucleoplasm;cytosol;cytoplasmic stress granule;nuclear speck
• Molecular function: RNA binding;mRNA 3'-UTR binding;protein binding;miRNA binding