MORC2

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

Basic information

Region (hg38): 22:30925129-30968774

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 (603 variants)
• not provided (153 variants)
• Inborn genetic diseases (66 variants)
• Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (35 variants)
• not specified (11 variants)
• MORC2-related condition (8 variants)
• Charcot-Marie-Tooth disease (5 variants)
• Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy;Charcot-Marie-Tooth disease axonal type 2Z (3 variants)
• Charcot-Marie-Tooth disease axonal type 2Z;Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (3 variants)
• Neurodevelopmental disorder (2 variants)
• See cases (2 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant (1 variants)
• Global developmental delay (1 variants)
• Tip-toe gait (1 variants)
• MORC2-related developmental disorder (1 variants)
• Distal spinal muscular atrophy (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.

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			3	142	11	156
missense	9	14	282	13		318
nonsense			10			10
start loss			1			1
frameshift			6			6
inframe indel			7			7
splice donor/acceptor (+/-2bp)			5			5
splice region			34	27	1	62
non coding			10	113	29	152
Total	9	14	324	268	40

Variants in MORC2

This is a list of pathogenic ClinVar variants found in the MORC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-30926746-C-A			Likely benign (Aug 30, 2018)
22-30926808-C-A		Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy	Uncertain significance (Sep 03, 2021)
22-30926820-T-C		Charcot-Marie-Tooth disease axonal type 2Z	Uncertain significance (Aug 28, 2023)
22-30926821-G-A		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Dec 09, 2023)
22-30926821-G-T		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Feb 22, 2017)
22-30926836-G-C		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Sep 08, 2023)
22-30926838-C-T		Charcot-Marie-Tooth disease axonal type 2Z	Uncertain significance (Dec 14, 2023)
22-30926839-G-A		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Oct 22, 2023)
22-30926856-T-C		Charcot-Marie-Tooth disease axonal type 2Z	Uncertain significance (Feb 24, 2022)
22-30926871-C-T		Charcot-Marie-Tooth disease axonal type 2Z;Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy	Likely pathogenic (Jun 20, 2022)
22-30926875-G-C		Charcot-Marie-Tooth disease axonal type 2Z • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 22, 2023)
22-30926880-G-A		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Feb 20, 2022)
22-30926880-G-C		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Oct 13, 2023)
22-30926886-G-T		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Apr 21, 2022)
22-30926890-G-A		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Apr 15, 2023)
22-30927064-C-A			Benign (Jul 26, 2018)
22-30927797-G-A			Benign (Aug 02, 2018)
22-30927913-G-C			Benign (Jul 06, 2018)
22-30928000-G-C		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (May 02, 2023)
22-30928009-CC-AA		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Jun 05, 2023)
22-30928010-C-G		Charcot-Marie-Tooth disease axonal type 2Z • Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy	Benign (Jan 15, 2024)
22-30928011-G-A		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Nov 11, 2021)
22-30928012-G-A		Charcot-Marie-Tooth disease axonal type 2Z	Likely benign (Nov 27, 2023)
22-30928013-G-C		Charcot-Marie-Tooth disease axonal type 2Z	Uncertain significance (Oct 28, 2023)
22-30928021-C-G		Charcot-Marie-Tooth disease axonal type 2Z	Uncertain significance (Mar 07, 2023)

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