GEMIN5

gem nuclear organelle associated protein 5, the group of WD repeat domain containing|Gemins

Basic information

Region (hg38): 5:154887410-154938211

Links

ENSG00000082516 ∙ NCBI:25929 ∙ OMIM:607005 ∙ HGNC:20043 ∙ Uniprot:Q8TEQ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (Strong), mode of inheritance: AR
• neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the GEMIN5 gene.

• 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				5		5
missense		3	102	14	5	124
nonsense	1	2	2			5
start loss						0
frameshift	3	2	1			6
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		1				1
splice region			2			2
non coding			1			1
Total	4	9	107	19	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	Uncertain significance (May 02, 2022)
5-154888257-C-T		Inborn genetic diseases	Uncertain significance (Aug 19, 2023)
5-154888306-A-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2022)
5-154888309-G-C			Likely benign (May 01, 2022)
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)
5-154889328-C-T		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
5-154889364-G-A			Uncertain significance (Feb 16, 2023)
5-154889392-A-C			Benign (Jul 13, 2018)
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)
5-154891341-G-A		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
5-154891385-G-A		Inborn genetic diseases	Uncertain significance (Jul 13, 2022)
5-154891403-A-G		GEMIN5-related disorder	Likely pathogenic (Jan 27, 2023)
5-154891427-A-T		Inborn genetic diseases	Uncertain significance (Oct 21, 2022)
5-154891451-C-T		Inborn genetic diseases	Likely benign (Jun 24, 2022)
5-154891455-C-T			Benign (Jul 13, 2018)
5-154891467-T-C		Inborn genetic diseases	Uncertain significance (Sep 15, 2022)
5-154891529-T-TG		Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction	Likely pathogenic (Jan 21, 2022)
5-154891536-T-A		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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