GMNN

geminin DNA replication inhibitor

Basic information

Region (hg38): 6:24774930-24786099

Links

ENSG00000112312 ∙ NCBI:51053 ∙ OMIM:602842 ∙ HGNC:17493 ∙ Uniprot:O75496 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meier-Gorlin syndrome 6 (Strong), mode of inheritance: AD
• Meier-Gorlin syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meier-Gorlin syndrome 6	AD	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	Craniofacial; Musculoskeletal; Neurologic	26637980

ClinVar

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

• not provided (64 variants)
• Inborn genetic diseases (6 variants)
• Meier-Gorlin syndrome 6 (4 variants)
• Meier-Gorlin syndrome (3 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GMNN 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				9	2	11
missense		1	22	5	4	32
nonsense	1					1
start loss						0
frameshift	1		1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2		1	3
non coding			1	7	13	21
Total	2	1	25	21	19

Variants in GMNN

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

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

Position	Type	Phenotype	Significance	ClinVar
6-24777238-A-G		GMNN-related disorder	Benign (Jul 23, 2019)
6-24777258-T-C			Likely benign (May 09, 2018)
6-24777262-A-T		Meier-Gorlin syndrome • Meier-Gorlin syndrome 6	Pathogenic (Jun 17, 2015)
6-24777278-AAATC-A		Meier-Gorlin syndrome • Meier-Gorlin syndrome 6	Pathogenic (Jun 17, 2015)
6-24777289-A-C			Likely benign (Nov 02, 2023)
6-24777296-A-G		Meier-Gorlin syndrome • Meier-Gorlin syndrome 6	Likely pathogenic (Jun 17, 2015)
6-24777308-G-C			Likely benign (Jul 23, 2023)
6-24777314-CTT-C			Likely benign (Aug 14, 2023)
6-24780497-C-T			Benign (Nov 12, 2018)
6-24780664-A-C		GMNN-related disorder	Benign (Jan 31, 2024)
6-24780673-T-G			Uncertain significance (Jun 15, 2023)
6-24780675-C-T			Conflicting classifications of pathogenicity (Apr 01, 2024)
6-24780684-A-G			Uncertain significance (May 16, 2022)
6-24780702-C-G			Uncertain significance (Jun 29, 2023)
6-24780716-A-C			Benign (Jan 29, 2024)
6-24780731-AG-A			Uncertain significance (Jul 03, 2022)
6-24780752-A-G			Likely benign (Feb 28, 2022)
6-24780759-A-C			Likely benign (Jan 08, 2023)
6-24780797-A-G			Benign (Nov 12, 2018)
6-24781011-G-C			Benign (Nov 12, 2018)
6-24781239-A-AAAT			Benign (Jun 20, 2021)
6-24781483-G-A			Uncertain significance (Oct 23, 2023)
6-24781491-G-C			Benign (Jan 29, 2024)
6-24781505-A-G		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
6-24781507-C-T			Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GMNN	protein_coding	protein_coding	ENST00000230056	6	11169

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.115	0.861	125714	0	9	125723	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.991	76	105	0.727	0.00000512	1371
Missense in Polyphen		13	31.984	0.40645		458
Synonymous	0.734	33	38.8	0.850	0.00000202	385
Loss of Function	1.93	3	9.39	0.319	3.94e-7	136

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000631	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000528
Middle Eastern	0.000116	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.
• Disease: DISEASE: Meier-Gorlin syndrome 6 (MGORS6) [MIM:616835]: A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. {ECO:0000269|PubMed:26637980}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: DNA Replication;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA Replication;G1/S Transition;CDT1 association with the CDC6:ORC:origin complex;Assembly of the pre-replicative complex;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.180

Intolerance Scores

• loftool: 0.553
• rvis_EVS: 0.99
• rvis_percentile_EVS: 90.52

Haploinsufficiency Scores

• pHI: 0.428
• hipred: Y
• hipred_score: 0.739
• ghis: 0.418

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.706

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gmnn
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; vision/eye phenotype; hematopoietic system phenotype; reproductive system phenotype; normal 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); embryo phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: gmnn
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: lacks all parts of type

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;regulation of DNA replication;negative regulation of DNA replication;animal organ morphogenesis;positive regulation of chromatin binding;negative regulation of cell cycle;negative regulation of transcription, DNA-templated;DNA replication preinitiation complex assembly;negative regulation of DNA-dependent DNA replication
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: chromatin binding;transcription corepressor activity;protein binding;histone deacetylase binding;repressing transcription factor binding