GEMIN4

gem nuclear organelle associated protein 4, the group of Minor histocompatibility antigens|Gemins

Basic information

Region (hg38): 17:744420-753999

Links

ENSG00000179409 ∙ NCBI:50628 ∙ OMIM:606969 ∙ HGNC:15717 ∙ Uniprot:P57678 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (Strong), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (Limited), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities	AR	Renal	The condition can include renal manifestations, including hydronephrosis, renal stones, nephrocalcinosis, and secondary hypertension, and awareness may allow early management of renal-related manifestations	Neurologic; Ophthalmologic; Renal	25558065; 27878435; 30237576

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GEMIN4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GEMIN4 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				25	8	33
missense		1	94	15	17	127
nonsense			5			5
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	1	101	40	26

Variants in GEMIN4

This is a list of pathogenic ClinVar variants found in the GEMIN4 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-744896-T-A		not specified	Uncertain significance (Jun 13, 2024)
17-744900-C-T		not specified	Uncertain significance (Dec 04, 2023)
17-744904-G-A		not specified	Uncertain significance (Jun 07, 2024)
17-744916-C-T		GEMIN4-related disorder	Benign/Likely benign (May 01, 2023)
17-744917-G-A		GEMIN4-related disorder	Benign (Oct 17, 2019)
17-744928-C-G		not specified	Uncertain significance (May 14, 2024)
17-744946-G-A		Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities	Benign (Jul 14, 2021)
17-744949-G-A		Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities	Uncertain significance (Nov 20, 2020)
17-744953-G-A			Likely benign (Jan 01, 2023)
17-744975-C-T		Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities • not specified	Conflicting classifications of pathogenicity (Jul 01, 2022)
17-745011-C-T		Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities	Uncertain significance (Sep 08, 2022)
17-745039-A-G			Benign (Dec 31, 2019)
17-745069-T-C			Benign (Apr 01, 2024)
17-745087-C-G		not specified	Uncertain significance (Sep 06, 2022)
17-745108-A-G		not specified	Uncertain significance (May 27, 2022)
17-745119-G-T		not specified	Uncertain significance (Mar 05, 2024)
17-745160-G-A			Likely benign (Mar 01, 2023)
17-745179-C-T		not specified	Uncertain significance (Jul 09, 2021)
17-745187-G-C		not specified	Uncertain significance (Apr 27, 2022)
17-745205-A-C		not specified	Uncertain significance (Aug 02, 2022)
17-745208-G-T		GEMIN4-related disorder	Likely benign (Feb 21, 2019)
17-745211-A-G		GEMIN4-related disorder	Likely benign (Oct 21, 2019)
17-745258-C-T		Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities	Benign (Jul 14, 2021)
17-745306-C-T			Benign (Dec 31, 2019)
17-745341-T-C		not specified	Uncertain significance (Aug 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GEMIN4	protein_coding	protein_coding	ENST00000319004	2	9586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.90e-13	0.585	124514	0	187	124701	0.000750

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.468	626	594	1.05	0.0000357	6872
Missense in Polyphen		212	195.88	1.0823		2584
Synonymous	-1.37	293	265	1.11	0.0000175	2176
Loss of Function	1.52	24	33.5	0.716	0.00000171	372

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00124	0.00123
Ashkenazi Jewish	0.000406	0.000398
East Asian	0.000894	0.000890
Finnish	0.000758	0.000743
European (Non-Finnish)	0.000666	0.000655
Middle Eastern	0.000894	0.000890
South Asian	0.00118	0.00118
Other	0.00101	0.000990

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. 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. 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. {ECO:0000269|PubMed:18984161}.
• Disease: DISEASE: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (NEDMCR) [MIM:617913]: An autosomal recessive, severe neurodevelopmental disorder characterized by global developmental delay since infancy, microcephaly, poor or absent speech, and inability to walk or spasticity. Additional features include renal abnormalities, congenital cataracts, gastroesophageal reflux disease, seizures with onset in infancy or childhood, hyporeflexia, and non-specific white matter abnormalities on brain imaging. {ECO:0000269|PubMed:25558065}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - Homo sapiens (human);snRNP Assembly;Metabolism of RNA;Metabolism of non-coding RNA (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.936
• rvis_EVS: 3.4
• rvis_percentile_EVS: 99.45

Haploinsufficiency Scores

• pHI: 0.402
• hipred: N
• hipred_score: 0.442
• ghis: 0.464

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.753

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gemin4
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: spliceosomal snRNP assembly;rRNA processing;import into nucleus
• Cellular component: nucleoplasm;nucleolus;cytoplasm;cytosol;membrane;nuclear body;small nuclear ribonucleoprotein complex;SMN complex;SMN-Sm protein complex;extracellular exosome;Gemini of coiled bodies
• Molecular function: protein binding