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Intellectual disability v6.11 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMC3.
Intellectual disability v6.11 PSMC3 Sarah Leigh reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.10 PSMC3 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMC3.
Source NHS GMS was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: This gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".; to: Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can be promoted to green rating at the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.; to: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. They were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder was identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.; to: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PSMC3.
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from neurodevelopmental delay to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.240 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.240 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to PMID: 37256937
Intellectual disability v5.239 PSMC3 Achchuthan Shanmugasundram reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32500975, 37256937; Phenotypes: ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.191 PSMC3 Dmitrijs Rots gene: PSMC3 was added
gene: PSMC3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to PMID: 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental delay
Mode of pathogenicity for gene: PSMC3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PSMC3 was set to GREEN
Added comment: 23 individuals with NDD due to 15 different de novo missense variants in PMID: 37256937.
Sources: Literature