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Intellectual disability
Gene: UPF1

UPF1 (UPF1, RNA helicase and ATPase)
EnsemblGeneIds (GRCh38): ENSG00000005007
EnsemblGeneIds (GRCh37): ENSG00000005007
OMIM: 601430, Gene2Phenotype
UPF1 is in 2 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.

Panel Version: 9.299

Created: 12 Mar 2026, 1:33 p.m.
Last Modified: 12 Mar 2026, 1:33 p.m.
Panel version: 9.299

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of monoallelic UPF1 variants with intellectual disability and/or global developmental delay. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 8 Sep 2025, 7:08 p.m. | Last Modified: 8 Sep 2025, 7:08 p.m.

Panel Version: 9.89

PMID:28135719 (2017) reported four unrelated patients with de novo heterozygous missense variants in UPF1 gene from the Deciphering Developmental Disorders Study cohort, for which no detailed phenotypic information was available in the publication. Three patients were reported with global developmental delay (mild in one) and the fourth patient was reported with neurodevelopmental delay as one of the presenting phenotypes in the Decipher database (https://www.deciphergenomics.org/gene/UPF1/patient-overlap/snvs)

PMID:28539120 (2017) reported a patient with significant intellectual disability (ID) and gross motor delay and with a heterozygous likely pathogenic variant in UPF1 gene (c.1576_1577delinsAA/ p.Ala526Asn). However, this patient also harboured a heterozygous likely pathogenic variant in SQSTM1 gene. As reviewed below by Ivone Leong, the authors suggested that it is plausible that the haploinsufficiency of SQSTM1 may have caused neurofunctional defects, which the haploinsufficiency of UPF1 may have exacerbated.

PMID:39571789 (2024) reported two unrelated paediatric patients with intellectual disabilities, frontal bossing, hypertelorism, high frontal hairline, and thin upper lip. They both had language and motor delays and were identified with de novo heterozygous variants in UPF1 gene (c.949_951del/ p.Asp317del & c.1984G>A/ p.Asp662Asn). The p.Asp662Asn variant has also been previously reported in a patient from PMID:28135719.

PMID:39993774 (2025) reported a 17‐year‐old male patient with moderate intellectual disability, atypical autism, ADHD, and aggressivity. He was identified with a de novo missense variant in UPF1 gene - c.1576G>A/ p.Ala526Thr.

As reviewed by Karen Stals, there is an additional patient identified with UPF1 variant in Exeter Genomics Laboratory.

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM.
Created: 8 Sep 2025, 6:55 p.m. | Last Modified: 8 Sep 2025, 7:04 p.m.

Panel Version: 9.87

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

Created: 8 Sep 2025, 6:55 p.m.
Last Modified: 8 Sep 2025, 7:04 p.m.
Panel version: 9.85

Karen Stals (Royal Devon and Exeter Hospital)

Green List (high evidence)

At least 4 individuals described in the literature with de novo variants in this gene and a neurodevelopmental disorder. Additional patient identified in Exeter. Moderate gene-disease association in Gene2Phenotype.
Created: 20 Aug 2025, 4:48 p.m. | Last Modified: 20 Aug 2025, 4:49 p.m.

Panel Version: 9.64

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental delay; autism; intellectual disability; speech delay

Publications

PMID: 39993774
PMID: 39571789
PMID: 28539120

Variants in this GENE are reported as part of current diagnostic practice

Created: 20 Aug 2025, 4:48 p.m.
Last Modified: 20 Aug 2025, 4:49 p.m.
Panel version: 9.64

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics).

PMID: 28539120 describes a patient with significant ID. The patient has SNVs in SQSTM1 and UPF1. The authors suggests that it is plausible that the haploinsufficiency of SQSTM1 may have caused neurofunctional defects, which the haploinsufficiency of UPF1 may have exacerbated.

As the patient in the second case has another variant in another gene, there is not enough evidence to support a gene-disease association so this gene has been given an Amber rating.
Created: 4 Dec 2020, 3:20 p.m. | Last Modified: 4 Dec 2020, 3:20 p.m.

Panel Version: 3.599

Created: 4 Dec 2020, 3:20 p.m.
Last Modified: 4 Dec 2020, 3:20 p.m.
Panel version: 3.599

Zornitza Stark (Australian Genomics)

I don't know

PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Created: 4 Nov 2020, 9:38 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental disorders

Publications

33057194

Created: 4 Nov 2020, 9:38 a.m.

Panel version: 3.510

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS

Phenotypes

neurodevelopmental disorder, MONDO:0700092
intellectual disability, MONDO:0001071

Tags

gene-checked

OMIM

601430

Clinvar variants

Variants in UPF1

Penetrance

None

Publications

Panels with this gene

History Filter Activity

20 Mar 2026, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked tag was added to gene: UPF1.

12 Mar 2026, Gel status: 3

Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green was removed from gene: UPF1. Tag Q3_25_NHS_review was removed from gene: UPF1.

12 Mar 2026, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to UPF1. Source Expert Review Green was added to UPF1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

8 Sep 2025, Gel status: 2