MORC2

MORC family CW-type zinc finger 2, the group of Zinc fingers CW-type

Basic information

Region (hg38): 22:30925130-30968774

Previous symbols: [ "ZCWCC1" ]

Links

ENSG00000133422 ∙ NCBI:22880 ∙ OMIM:616661 ∙ HGNC:23573 ∙ Uniprot:Q9Y6X9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease axonal type 2Z (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2Z (Strong), mode of inheritance: AD
• developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (Strong), mode of inheritance: AD
• Leigh syndrome (Limited), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2Z (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease type, axonal, type 2Z; Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy	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	26497905; 27105897; 28771897; 32693025

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MORC2 gene.

• Charcot-Marie-Tooth disease axonal type 2Z (8 variants)
• not provided (3 variants)
• Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (3 variants)
• Charcot-Marie-Tooth disease (2 variants)
• Inborn genetic diseases (2 variants)
• Global developmental delay (1 variants)
• MORC2-related disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• MORC2-related neurodevelopmental disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MORC2 gene is commonly pathogenic or not. These statistics are base on trasncript: . 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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	162	11	179
missense	10	18	343	13		384
nonsense			10			10
start loss			1			1
frameshift			7			7
splice donor/acceptor (+/-2bp)			7			7
Total	10	18	374	175	11

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MORC2	protein_coding	protein_coding	ENST00000215862	23	43168

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000144	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.23	376	598	0.629	0.0000374	6328
Missense in Polyphen		59	154.44	0.38203		1825
Synonymous	0.959	203	221	0.918	0.0000129	1903
Loss of Function	6.31	6	57.8	0.104	0.00000335	625

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00000886	0.00000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864). May act as a transcriptional repressor (PubMed:20225202). Down-regulates CA9 expression (PubMed:20110259). {ECO:0000269|PubMed:20110259, ECO:0000269|PubMed:20225202, ECO:0000269|PubMed:24286864}.
• Pathway: Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• rvis_EVS: -1.68
• rvis_percentile_EVS: 2.63

Haploinsufficiency Scores

• pHI: 0.416
• hipred: Y
• hipred_score: 0.626
• ghis: 0.628

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Morc2a
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; embryo phenotype

Gene ontology

• Biological process: fatty acid metabolic process
• Cellular component: nucleus;cytosol
• Molecular function: zinc ion binding