UPF3B

UPF3B regulator of nonsense mediated mRNA decay, the group of DECID complex

Basic information

Region (hg38): X:119834021-119852998

Previous symbols: [ "MRX62", "UPF3BP1", "UPF3BP2", "UPF3BP3" ]

Links

ENSG00000125351 ∙ NCBI:65109 ∙ OMIM:300298 ∙ HGNC:20439 ∙ Uniprot:Q9BZI7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability 14 (Definitive), mode of inheritance: XLR
• X-linked intellectual disability with marfanoid habitus (Supportive), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability 14 (Moderate), mode of inheritance: XL
• syndromic X-linked intellectual disability 14 (Definitive), mode of inheritance: XL
• syndromic X-linked intellectual disability 14 (Strong), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic 14	XL	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; Musculoskeletal; Neurologic	9805132; 17704778; 19377476; 22957832
Nonsyndromic forms have been described in addition to the initial reports of individuals with syndromic mental retardation

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UPF3B gene.

• Syndromic X-linked intellectual disability 14 (126 variants)
• not provided (73 variants)
• Inborn genetic diseases (37 variants)
• not specified (11 variants)
• UPF3B-related condition (2 variants)
• Intellectual disability (2 variants)
• Neurodevelopmental disorder (2 variants)
• Cataract;Microcephaly;Severe global developmental delay (1 variants)
• UPF3B-associated intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UPF3B 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	22	3	26
missense			57	6	4	67
nonsense	2	5				7
start loss	1					1
frameshift	12	1	1			14
inframe indel			6			6
splice donor/acceptor (+/-2bp)			2			2
splice region		1	2	7	1	11
non coding				36	28	64
Total	15	6	67	64	35

Highest pathogenic variant AF is 0.0000180

Variants in UPF3B

This is a list of pathogenic ClinVar variants found in the UPF3B region.

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

Position	Type	Phenotype	Significance	ClinVar
X-119834890-T-C		Syndromic X-linked intellectual disability 14	Likely benign (Apr 25, 2023)
X-119834909-A-T		Inborn genetic diseases	Uncertain significance (Jan 14, 2020)
X-119834925-T-C			Uncertain significance (Aug 15, 2023)
X-119834946-C-CA		Syndromic X-linked intellectual disability 14	Uncertain significance (Feb 26, 2023)
X-119834950-C-G			Uncertain significance (Dec 01, 2022)
X-119834958-T-C		UPF3B-related disorder • Syndromic X-linked intellectual disability 14	Uncertain significance (Aug 31, 2023)
X-119834978-C-T		Syndromic X-linked intellectual disability 14	Uncertain significance (May 25, 2022)
X-119834978-CG-C		Syndromic X-linked intellectual disability 14	Pathogenic (Nov 08, 2017)
X-119835001-T-C		Inborn genetic diseases	Likely benign (Jan 05, 2018)
X-119835046-T-C		Syndromic X-linked intellectual disability 14	Likely benign (Nov 05, 2022)
X-119835112-A-C			Benign (Jun 14, 2018)
X-119837476-C-T			Benign (Feb 05, 2019)
X-119837615-CA-C			Benign (Aug 15, 2019)
X-119837615-C-CA			Benign (Aug 15, 2019)
X-119837615-C-CAA			Likely benign (Aug 26, 2019)
X-119837749-A-G		Syndromic X-linked intellectual disability 14	Benign/Likely benign (Jan 01, 2023)
X-119837751-C-T		Syndromic X-linked intellectual disability 14	Uncertain significance (Jul 24, 2021)
X-119837770-C-T			Uncertain significance (Nov 01, 2022)
X-119837771-G-A		Syndromic X-linked intellectual disability 14	Pathogenic (Jun 05, 2023)
X-119837773-T-C			Uncertain significance (Aug 09, 2018)
X-119837784-C-G			Uncertain significance (Jun 01, 2017)
X-119837785-ACTT-A		Neurodevelopmental disorder	Uncertain significance (Oct 24, 2023)
X-119837792-CTTT-C		Syndromic X-linked intellectual disability 14	Uncertain significance (Dec 18, 2022)
X-119837793-TTTC-T			Uncertain significance (Apr 01, 2023)
X-119837794-T-C		Inborn genetic diseases • Syndromic X-linked intellectual disability 14	Uncertain significance (Dec 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UPF3B	protein_coding	protein_coding	ENST00000276201	11	18977

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0150	125737	2	0	125739	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	112	182	0.615	0.0000139	3225
Missense in Polyphen		31	72.527	0.42743		1281
Synonymous	-0.450	63	58.6	1.07	0.00000414	808
Loss of Function	3.90	2	21.6	0.0928	0.00000188	368

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000245	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2- UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);RNA transport - Homo sapiens (human);Gene expression (Transcription);RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Nonsense-Mediated Decay (NMD);Transport of Mature mRNA derived from an Intron-Containing Transcript;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.440
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.22

Haploinsufficiency Scores

• pHI: 0.262
• hipred: Y
• hipred_score: 0.825
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.401

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Upf3b
• Phenotype: cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;mRNA splicing, via spliceosome;RNA export from nucleus;mRNA export from nucleus;mRNA 3'-end processing;positive regulation of translation
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;microtubule organizing center;cytosol;exon-exon junction complex
• Molecular function: RNA binding;mRNA binding;protein binding;structural constituent of nuclear pore