GEMIN5
Basic information
Region (hg38): 5:154887411-154938211
Links
Phenotypes
GenCC
Source:
- neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction | AR | 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 | Neurologic | 33963192 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (3 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GEMIN5 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 | 6 | |||||
missense | 160 | 17 | 185 | |||
nonsense | 5 | |||||
start loss | 0 | |||||
frameshift | 7 | |||||
inframe indel | 2 | |||||
splice donor/acceptor (+/-2bp) | 4 | |||||
splice region | 2 | 2 | ||||
non coding | 1 | |||||
Total | 4 | 14 | 164 | 23 | 5 |
Variants in GEMIN5
This is a list of pathogenic ClinVar variants found in the GEMIN5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
5-154888238-C-T | Inborn genetic diseases | Likely benign (Nov 22, 2021) | ||
5-154888240-G-GT | Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction | Conflicting classifications of pathogenicity (Sep 20, 2024) | ||
5-154888250-G-A | Inborn genetic diseases | Uncertain significance (Sep 08, 2024) | ||
5-154888257-C-T | Inborn genetic diseases | Uncertain significance (Aug 19, 2023) | ||
5-154888273-C-G | Inborn genetic diseases | Uncertain significance (Nov 07, 2024) | ||
5-154888306-A-C | Inborn genetic diseases | Uncertain significance (Aug 12, 2022) | ||
5-154888309-G-C | Likely benign (May 01, 2022) | |||
5-154888319-T-A | Uncertain significance (Mar 22, 2024) | |||
5-154888341-C-T | Inborn genetic diseases | Likely benign (Jul 13, 2021) | ||
5-154888359-C-T | Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction | Uncertain significance (-) | ||
5-154888360-A-C | Inborn genetic diseases | Uncertain significance (Apr 28, 2022) | ||
5-154888361-T-G | Inborn genetic diseases | Uncertain significance (May 16, 2023) | ||
5-154889320-C-A | GEMIN5-related disorder | Likely pathogenic (Jul 20, 2021) | ||
5-154889326-T-C | Inborn genetic diseases | Likely benign (Nov 25, 2024) | ||
5-154889328-C-T | Inborn genetic diseases | Uncertain significance (Sep 16, 2021) | ||
5-154889331-T-C | Uncertain significance (Dec 28, 2022) | |||
5-154889364-G-A | Uncertain significance (Feb 16, 2023) | |||
5-154889365-T-C | Inborn genetic diseases | Uncertain significance (Jul 26, 2024) | ||
5-154889392-A-C | Benign (Jul 13, 2018) | |||
5-154889394-A-G | Inborn genetic diseases | Uncertain significance (Oct 24, 2024) | ||
5-154889409-T-C | Inborn genetic diseases | Uncertain significance (Jul 05, 2024) | ||
5-154889418-C-G | Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction | Likely pathogenic (Nov 01, 2024) | ||
5-154889421-G-C | Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction | Uncertain significance (Jul 21, 2023) | ||
5-154891257-T-G | Likely benign (Feb 01, 2023) | |||
5-154891327-T-C | Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction | Benign/Likely benign (May 17, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
GEMIN5 | protein_coding | protein_coding | ENST00000285873 | 28 | 50794 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.24e-21 | 1.00 | 125600 | 0 | 147 | 125747 | 0.000585 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.0677 | 781 | 786 | 0.993 | 0.0000395 | 9816 |
Missense in Polyphen | 223 | 248.38 | 0.89782 | 3106 | ||
Synonymous | -0.767 | 314 | 297 | 1.06 | 0.0000155 | 2907 |
Loss of Function | 3.43 | 47 | 80.1 | 0.587 | 0.00000404 | 948 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00180 | 0.00180 |
Ashkenazi Jewish | 0.0000993 | 0.0000992 |
East Asian | 0.000553 | 0.000544 |
Finnish | 0.000328 | 0.000323 |
European (Non-Finnish) | 0.000538 | 0.000519 |
Middle Eastern | 0.000553 | 0.000544 |
South Asian | 0.00105 | 0.00101 |
Other | 0.000496 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Required for the assembly of the SMN complex that plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:16857593, PubMed:18984161, PubMed:20513430). Thereby, plays an important role in the splicing of cellular pre- mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:18984161). Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus (PubMed:18984161). GEMIN5 acts as the snRNA-binding protein of the SMN complex (PubMed:11714716, PubMed:16857593, PubMed:19377484, PubMed:19750007, PubMed:20513430, PubMed:27834343, PubMed:27881600, PubMed:27881601). Binds to the 7-methylguanosine cap of RNA molecules (PubMed:19750007, PubMed:27834343, PubMed:27881600, PubMed:27881601, Ref.25). Binds to the 3'-UTR of SMN1 mRNA and regulates its translation; does not affect mRNA stability (PubMed:25911097). May play a role in the regulation of protein synthesis via its interaction with ribosomes (PubMed:27507887). {ECO:0000269|PubMed:11714716, ECO:0000269|PubMed:16857593, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:19377484, ECO:0000269|PubMed:19750007, ECO:0000269|PubMed:20513430, ECO:0000269|PubMed:25911097, ECO:0000269|PubMed:27507887, ECO:0000269|PubMed:27834343, ECO:0000269|PubMed:27881600, ECO:0000269|PubMed:27881601, ECO:0000269|Ref.25}.;
- Pathway
- RNA transport - Homo sapiens (human);snRNP Assembly;Metabolism of RNA;Metabolism of non-coding RNA
(Consensus)
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- loftool
- 0.948
- rvis_EVS
- 0.22
- rvis_percentile_EVS
- 68.14
Haploinsufficiency Scores
- pHI
- 0.403
- hipred
- Y
- hipred_score
- 0.616
- ghis
- 0.573
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.702
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gemin5
- Phenotype
Zebrafish Information Network
- Gene name
- gemin5
- Affected structure
- thymus
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- spliceosomal snRNP assembly;mRNA splicing, via spliceosome;translation;regulation of translation;import into nucleus;protein-containing complex assembly
- Cellular component
- nucleoplasm;cytoplasm;cytosol;membrane;nuclear body;cytosolic large ribosomal subunit;SMN complex;SMN-Gemin2 complex;SMN-Sm protein complex;Gemini of coiled bodies
- Molecular function
- RNA 7-methylguanosine cap binding;RNA binding;mRNA 3'-UTR binding;protein binding;snRNA binding;U1 snRNA binding;U4 snRNA binding;U4atac snRNA binding;ribosome binding