GMNN

geminin DNA replication inhibitor

Basic information

Region (hg38): 6:24774931-24786099

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
Meier-Gorlin syndrome 6 (Strong), 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 (74 variants)
Inborn_genetic_diseases (16 variants)
Meier-Gorlin_syndrome_6 (8 variants)
Meier-Gorlin_syndrome (3 variants)
not_specified (3 variants)
GMNN-related_disorder (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. These statistics are base on transcript: NM_000015895.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	16 clinvar		17
missense		1 clinvar	36 clinvar	9 clinvar	3 clinvar	49
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	1 clinvar		5 clinvar			6
splice donor/acceptor (+/-2bp)						0
Total	2	1	43	25	3

Loading clinvar variants...

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