MAPRE2

microtubule associated protein RP/EB family member 2, the group of Microtubule associated protein RP/EB family

Basic information

Region (hg38): 18:34976927-35143470

Links

ENSG00000166974 ∙ NCBI:10982 ∙ OMIM:605789 ∙ HGNC:6891 ∙ Uniprot:Q15555 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple benign circumferential skin creases on limbs 1 (Definitive), mode of inheritance: AR
• skin creases, congenital symmetric circumferential, 2 (Moderate), mode of inheritance: AD
• multiple benign circumferential skin creases on limbs (Supportive), mode of inheritance: AD
• skin creases, congenital symmetric circumferential, 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital symmetric circumferential skin creases 2	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; Dermatologic; Neurologic	19182162; 21262397; 26637975

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAPRE2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPRE2 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	3	12
missense		2	8	2		12
nonsense		1				1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding						0
Total	0	4	8	11	3

Variants in MAPRE2

This is a list of pathogenic ClinVar variants found in the MAPRE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-34978515-GGAAT-G			Likely benign (Nov 01, 2023)
18-35005550-C-G		Inborn genetic diseases	Uncertain significance (Oct 11, 2021)
18-35005554-G-A		MAPRE2-related disorder	Uncertain significance (Jun 23, 2023)
18-35041565-C-T		Inborn genetic diseases	Uncertain significance (Jun 14, 2023)
18-35070189-T-C		Inborn genetic diseases	Uncertain significance (Jan 26, 2021)
18-35070228-G-A		MAPRE2-related disorder	Likely benign (Jun 25, 2019)
18-35070237-AGAGACTAT-A		Skin creases, congenital symmetric circumferential, 2	Likely pathogenic (Oct 01, 2018)
18-35070275-A-G		Skin creases, congenital symmetric circumferential, 2	Pathogenic (Dec 03, 2015)
18-35070330-A-T			Benign (Dec 31, 2019)
18-35097455-A-G		Skin creases, congenital symmetric circumferential, 2	Pathogenic (Dec 03, 2015)
18-35097462-A-G			Likely benign (Jan 18, 2024)
18-35097490-A-G		not specified	Uncertain significance (Mar 26, 2024)
18-35097562-G-A		Skin creases, congenital symmetric circumferential, 2	Uncertain significance (Sep 01, 2022)
18-35097564-A-T			Likely benign (Mar 29, 2018)
18-35097575-G-A		Skin creases, congenital symmetric circumferential, 2	Likely pathogenic (-)
18-35097582-C-T		MAPRE2-related disorder	Likely benign (Jun 20, 2019)
18-35101957-G-A			Likely benign (Mar 28, 2018)
18-35101976-C-T		Skin creases, congenital symmetric circumferential, 2 • Developmental disorder	Pathogenic/Likely pathogenic (Sep 26, 2022)
18-35101977-G-A		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
18-35102003-C-T		Skin creases, congenital symmetric circumferential, 2	Pathogenic (Dec 03, 2015)
18-35102022-A-G		Skin creases, congenital symmetric circumferential, 2	Uncertain significance (Jul 01, 2021)
18-35102044-G-A			Likely benign (Dec 31, 2019)
18-35102066-C-T		Skin creases, congenital symmetric circumferential, 2	Likely pathogenic (-)
18-35102067-G-A		Skin creases, congenital symmetric circumferential, 2	Likely pathogenic (Sep 01, 2022)
18-35102152-C-G			Likely benign (Jul 11, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPRE2	protein_coding	protein_coding	ENST00000300249	7	166543

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.834	0.166	125743	0	3	125746	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.19	59	179	0.330	0.00000907	2160
Missense in Polyphen		11	59.802	0.18394		836
Synonymous	0.408	67	71.4	0.939	0.00000418	592
Loss of Function	3.41	3	19.1	0.157	0.00000115	202

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000964	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes. May play a role in cell migration (By similarity). {ECO:0000250}.
• Disease: DISEASE: Skin creases, congenital symmetric circumferential, 2 (CSCSC2) [MIM:616734]: An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features. {ECO:0000269|PubMed:26637975}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.0882
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.809
• hipred: Y
• hipred_score: 0.825
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.939

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mapre2

Zebrafish Information Network

• Gene name: mapre2
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: signal transduction;cell population proliferation;regulation of microtubule polymerization or depolymerization;positive regulation of ARF protein signal transduction;protein localization to microtubule;positive regulation of GTPase activity;spindle assembly;cell division;positive regulation of keratinocyte migration;positive regulation of adherens junction organization;protein localization to microtubule plus-end
• Cellular component: cytoplasm;microtubule organizing center;microtubule;cytoplasmic microtubule;focal adhesion;microtubule cytoskeleton;microtubule plus-end;spindle midzone
• Molecular function: protein binding;microtubule binding;protein kinase binding;identical protein binding;microtubule plus-end binding