MORC2 (MORC family CW-type zinc finger 2)

Gene

• Entrez ID: 22880
• Gene name: MORC family CW-type zinc finger 2
• Gene symbol: MORC2
• Synonyms (NCBI Gene): CMT2Z, DIGFAN, ZCW3, ZCWCC1
• Chromosome: 22
• Chromosome location: 22q12.2
• Summary: This gene encodes a member of the Microrchidia (MORC) protein superfamily. The encoded protein is known to regulate the condensation of heterochromatin in response to DNA damage and play a role in repressing transcription. The protein has been found to re

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs749060708	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs864309503	G>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs864309504	G>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs886037934	T>C	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs1064795559	G>A	Uncertain-significance, likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs1064796495	C>A,G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs1163530787	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555938796	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-pathogenic	Missense variant, coding sequence variant
rs1602485958	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1602499631	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1602499659	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1602510200	C>T	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant
rs1602510214	G>A	Likely-pathogenic	5 prime UTR variant, missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT045739	hsa-miR-125a-5p	CLASH	23622248
MIRT039847	hsa-miR-615-3p	CLASH	23622248
MIRT497228	hsa-miR-3675-5p	PAR-CLIP	22291592
MIRT497227	hsa-miR-4742-5p	PAR-CLIP	22291592
MIRT497226	hsa-miR-4269	PAR-CLIP	22291592
MIRT497225	hsa-miR-6715b-5p	PAR-CLIP	22291592
MIRT497224	hsa-miR-4514	PAR-CLIP	22291592
MIRT497223	hsa-miR-4692	PAR-CLIP	22291592
MIRT497222	hsa-miR-877-3p	PAR-CLIP	22291592
MIRT497221	hsa-miR-6515-3p	PAR-CLIP	22291592
MIRT440220	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT440220	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT497228	hsa-miR-3675-5p	PAR-CLIP	22291592
MIRT497227	hsa-miR-4742-5p	PAR-CLIP	22291592
MIRT497226	hsa-miR-4269	PAR-CLIP	22291592
MIRT497225	hsa-miR-6715b-5p	PAR-CLIP	22291592
MIRT497224	hsa-miR-4514	PAR-CLIP	22291592
MIRT497223	hsa-miR-4692	PAR-CLIP	22291592
MIRT497222	hsa-miR-877-3p	PAR-CLIP	22291592
MIRT497221	hsa-miR-6515-3p	PAR-CLIP	22291592
MIRT2044497	hsa-miR-1184	CLIP-seq
MIRT2044498	hsa-miR-1238	CLIP-seq
MIRT2044499	hsa-miR-1301	CLIP-seq
MIRT2044500	hsa-miR-296-3p	CLIP-seq
MIRT2044501	hsa-miR-3184	CLIP-seq
MIRT2044502	hsa-miR-3665	CLIP-seq
MIRT2044503	hsa-miR-423-5p	CLIP-seq
MIRT2044504	hsa-miR-4660	CLIP-seq
MIRT2044505	hsa-miR-4688	CLIP-seq
MIRT2044506	hsa-miR-4691-5p	CLIP-seq
MIRT2044507	hsa-miR-4719	CLIP-seq
MIRT2044508	hsa-miR-4736	CLIP-seq
MIRT2044509	hsa-miR-486-3p	CLIP-seq
MIRT2044510	hsa-miR-5047	CLIP-seq
MIRT2044511	hsa-miR-548v	CLIP-seq
MIRT2044501	hsa-miR-3184	CLIP-seq
MIRT2044502	hsa-miR-3665	CLIP-seq
MIRT2044503	hsa-miR-423-5p	CLIP-seq
MIRT2044505	hsa-miR-4688	CLIP-seq
MIRT2044508	hsa-miR-4736	CLIP-seq
MIRT2044509	hsa-miR-486-3p	CLIP-seq
MIRT2273702	hsa-miR-541	CLIP-seq
MIRT2273703	hsa-miR-654-5p	CLIP-seq
MIRT2044500	hsa-miR-296-3p	CLIP-seq
MIRT2044501	hsa-miR-3184	CLIP-seq
MIRT2044502	hsa-miR-3665	CLIP-seq
MIRT2044503	hsa-miR-423-5p	CLIP-seq
MIRT2044505	hsa-miR-4688	CLIP-seq
MIRT2044508	hsa-miR-4736	CLIP-seq
MIRT2044509	hsa-miR-486-3p	CLIP-seq
MIRT2273702	hsa-miR-541	CLIP-seq
MIRT2273703	hsa-miR-654-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IDA	29440755
GO:0000792	Component	Heterochromatin	IDA	28581500
GO:0003682	Function	Chromatin binding	IDA	23260667, 29211708
GO:0005515	Function	Protein binding	IPI	28514442, 28581500, 33961781
GO:0005524	Function	ATP binding	IDA	29440755
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	23260667
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005737	Component	Cytoplasm	IDA	23260667
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0006338	Process	Chromatin remodeling	IDA	23260667
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006631	Process	Fatty acid metabolic process	IEA
GO:0006974	Process	DNA damage response	IDA	23260667
GO:0008270	Function	Zinc ion binding	IDA	29440755
GO:0008270	Function	Zinc ion binding	IEA
GO:0016363	Component	Nuclear matrix	IDA	23260667
GO:0016363	Component	Nuclear matrix	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IDA	23260667, 29440755
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0042802	Function	Identical protein binding	IPI	29440755
GO:0042803	Function	Protein homodimerization activity	IDA	29440755
GO:0046872	Function	Metal ion binding	IEA
GO:0140719	Process	Constitutive heterochromatin formation	IDA	28581500
GO:0141005	Process	Transposable element silencing by heterochromatin formation	IDA	29211708

Other IDs

• MIM: 616661
• HGNC: 23573
• e!Ensembl: ENSG00000133422

Protein

• UniProt ID: Q9Y6X9
• Protein name: ATPase MORC2 (EC 3.6.1.-) (MORC family CW-type zinc finger protein 2) (Zinc finger CW-type coiled-coil domain protein 1)
• Protein function: Essential for epigenetic silencing by the HUSH (human silencing hub) complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing (PubMed:28581500, PubMed:2944075
• PDB: 5OF9, 5OFA, 5OFB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13589	HATPase_c_3	26 → 169		Domain
  PF17942	Morc6_S5	323 → 451	Morc6 ribosomal protein S5 domain 2-like	Family
  PF07496	zf-CW	495 → 542	CW-type Zinc Finger	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in smooth muscle, pancreas and testis.
• Sequence:

  MAFTNYSSLNRAQLTFEYLHTNSTTHEFLFGALAELVDNARDADATRIDIYAERREDLRG
  GFMLCFLDDGAGMDPSDAASVIQFGKSAKRTPESTQIGQYGNGLKSGSMRIGKDFILFTK
  KEDTMTCLFLSRTFHEEEGIDEVIVPLPTWNARTREPVTDNVEKFAIETELIYKYSPFRT
  EEEVMTQFMKIPGDSGTLVIIFNLKLMDNGEPELDIISNPRDIQMAETSPEGTKPERRSF
  RAYAAVLYIDPRMRIFIHGHKVQTKRLSCCLYKPRMYKYTSSRFKTRAEQEVKKAEHVAR
  IAEEKAREAESKARTLEVRLGGDLTRDSRVMLRQVQNRAITLRREADVKKRIKEAKQRAL
  KEPKELNFVFGVNIEHRDLDGMFIYNCSRLIKMYEKVGPQLEGGMACGGVVGVVDVPYLV
  LEPTHNKQDFADAKEYRHLLRAMGEHLAQYWKDIAIAQRGIIKFWDEFGYLSANWNQPPS
  SELRYKRRRAMEIPTTIQCDLCLKWRTLPFQLSSVEKDYPDTWVCSMNPDPEQDRCEASE
  QKQKVPLGTFRKDMKTQEEKQKQLTEKIRQQQEKLEALQKTTPIRSQADLKKLPLEVTTR
  PSTEEPVRRPQRPRSPPLPAVIRNAPSRPPSLPTPRPASQPRKAPVISSTPKLPALAARE
  EASTSRLLQPPEAPRKPANTLVKTASRPAPLVQQLSPSLLPNSKSPREVPSPKVIKTPVV
  KKTESPIKLSPATPSRKRSVAVSDEEEVEEEAERRKERCKRGRFVVKEEKKDSNELSDSA
  GEEDSADLKRAQKDKGLHVEVRVNREWYTGRVTAVEVGKHVVRWKVKFDYVPTDTTPRDR
  WVEKGSEDVRLMKPPSPEHQSLDTQQEGGEEEVGPVAQQAIAVAEPSTSECLRIEPDTTA
  LSTNHETIDLLVQILRNCLRYFLPPSFPISKKQLSAMNSDELISFPLKEYFKQYEVGLQN
  LCNSYQSRADSRAKASEESLRTSERKLRETEEKLQKLRTNIVALLQKVQEDIDINTDDEL
  DAYIEDLITKGD

• Sequence length: 1032

Pathways

Reactome:

Fatty acyl-CoA biosynthesis

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Charcot-Marie-Tooth disease	Likely pathogenic; Pathogenic	rs864309503, rs864309504, rs886037934, rs1602485728	RCV000857122 RCV000857126 RCV000857125 RCV000857119
Charcot-Marie-Tooth disease axonal type 2Z	Likely pathogenic; Pathogenic	rs2147256596, rs1342054043, rs2517588823, rs864309503, rs864309504, rs886037934, rs2517589889, rs1064796495, rs1555938796, rs1555938741, rs1602496057, rs1602485728, rs1602499659, rs1602510200, rs1602510214, rs2040679845	RCV001932939 RCV002465008 RCV003050579 RCV000202547 RCV000202460 RCV000240855 RCV003593344 RCV003755402 RCV001856876 RCV000689169 RCV000817470 RCV000816128 RCV000820512 RCV001215495 RCV000857312 RCV002249596 RCV003333113 RCV001871631
Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy	Likely pathogenic; Pathogenic	rs773676225, rs1602496057, rs2147256596, rs2147284796, rs2517621673, rs1342054043, rs864309503, rs864309504, rs2517601712, rs1602510200, rs1602510214, rs2040679845	RCV001527637 RCV001706927 RCV005054387 RCV002273097 RCV002464984 RCV002465008 RCV003387804 RCV005055008 RCV004698894 RCV001281381 RCV001281380 RCV001281379
Distal spinal muscular atrophy	Likely pathogenic; Pathogenic	rs864309503	RCV000857123
Global developmental delay	Pathogenic	rs864309504	RCV001255406
MORC2-related disorder	Likely pathogenic; Pathogenic	rs1555938796, rs1602510200	RCV003983095 RCV003432987
MORC2-related neurodevelopmental disorders	Pathogenic	rs1602510200	RCV001796981
Neurodevelopmental disorder	Pathogenic	rs1602510200	RCV002272381

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign	rs16989204	RCV005897154
Cervical cancer	Benign	rs16989204	RCV005897157
Charcot-Marie-Tooth disease type 4	Uncertain significance	rs1602485471	RCV000857117
Charcot-Marie-Tooth disease, type I	Uncertain significance	rs1602477282, rs750686775	RCV000857115 RCV000857121
Cholangiocarcinoma	Uncertain significance	rs1214680334	RCV005900357
Clear cell carcinoma of kidney	Benign	rs16989204	RCV005897158
Colon adenocarcinoma	Uncertain significance	rs750003469	RCV005901967
Familial cancer of breast	Likely benign	rs779612677	RCV005931414
Hepatocellular carcinoma	Benign	rs5753394, rs16989204	RCV005915851 RCV005897155
Lung cancer	Benign	rs16989204	RCV005897163
Malignant lymphoma, large B-cell, diffuse	Benign	rs5753394	RCV005915852
Malignant tumor of esophagus	Benign	rs16989204	RCV005897156
Melanoma	Uncertain significance	rs1214680334	RCV005900356
MORC2-related developmental disorder	Conflicting classifications of pathogenicity	rs1064795559	RCV000991213
Neuronopathy, distal hereditary motor, autosomal dominant	Uncertain significance	rs548292999	RCV000857116
Ovarian serous cystadenocarcinoma	Benign	rs16989204	RCV005897159
See cases	Uncertain significance	rs762057484, rs764379949	RCV002252949 RCV003128415
Thymoma	Benign	rs16989204	RCV005897161
Thyroid cancer, nonmedullary, 1	Benign	rs16989204	RCV005897162
Tip-toe gait	Uncertain significance; Conflicting classifications of pathogenicity	rs764379949, rs781162787	RCV004723041 RCV001784225
Uterine carcinosarcoma	Benign	rs16989204	RCV005897160

Associations from Text Mining
Disease Name	Relationship Type	References
Alcoholic Neuropathy	Associate	35904125, 36791574
Breast Neoplasms	Associate	32112098, 33626175, 34974534, 35522895, 36793866
Carcinogenesis	Associate	30644437, 31180332, 36234785, 37737260
Carcinoma Renal Cell	Associate	37737260
Charcot Marie Tooth Disease	Associate	26659848, 28581500, 34189813, 34974534, 35904125
Charcot Marie Tooth disease Type 2B	Associate	34189813
Charcot Marie Tooth disease Type 2E	Associate	35904125
Cholangiocarcinoma	Stimulate	31180332
Cockayne Syndrome	Associate	36791574
Colorectal Neoplasms	Associate	25117815, 32749190
Colorectal Neoplasms	Stimulate	36234785
Developmental Disabilities	Associate	32693025, 34189813, 34974534, 36791574
DNA Repair Deficiency Disorders	Associate	36791574
Epileptic Encephalopathy Early Infantile 3	Associate	35904125
Facies	Associate	36791574
Genetic Diseases Inborn	Associate	32693025
Glioma	Associate	34913078
Graves Ophthalmopathy	Associate	36076300
Growth Disorders	Associate	32693025, 35904125, 36791574
Hereditary Sensory and Motor Neuropathy	Associate	26659848
Hypersensitivity Delayed	Associate	34189813
Inflammation	Inhibit	36234785
Intellectual Disability	Associate	32693025
Leigh Disease	Associate	32693025, 36675121
Lymphatic Metastasis	Associate	31180332
Lymphatic Metastasis	Stimulate	39312367
Microcephaly	Associate	32693025, 36791574
Muscle Weakness	Associate	33844363
Muscular Atrophy Spinal	Associate	32693025, 35904125, 36791574
Neoplasm Metastasis	Associate	31180332
Neoplasms	Associate	26098774, 32749190, 33626175, 34913078, 34974534, 35522895, 36234785, 36967563, 37352040
Neoplasms	Inhibit	37737260
Nervous System Diseases	Associate	32693025, 33844363
Neuromuscular Diseases	Associate	35904125
Peripheral Nervous System Diseases	Associate	35904125
Plagiocephaly and X linked mental retardation	Associate	32693025, 35904125
Reflex Abnormal	Associate	32693025
Retinal Diseases	Associate	32693025
Spastic Paraplegia Hereditary	Associate	26659848
Stomach Neoplasms	Associate	26098774, 29339121, 30644437
Syndrome	Associate	35904125
Triple Negative Breast Neoplasms	Associate	22140552, 37352040
Uterine Cervical Neoplasms	Associate	39312367