MORC1

Summary

MORC1 (MORC family CW-type zinc finger 1, HGNC:7198) is a protein-coding gene on chromosome 3q13.13, encoding MORC family CW-type zinc finger protein 1 (Q86VD1). Required for spermatogenesis.

This gene encodes the human homolog of mouse morc and like the mouse protein it is testis-specific. Mouse studies support a testis-specific function since only male knockout mice are infertile; infertility is the only apparent defect. These studies further support a role for this protein early in spermatogenesis, possibly by affecting entry into apoptosis because testis from knockout mice show greatly increased numbers of apoptotic cells.

Source: NCBI Gene 27136 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_014429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7198
Approved symbol	MORC1
Name	MORC family CW-type zinc finger 1
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Aliases	ZCW6, CT33
Ensembl gene	ENSG00000114487
Ensembl biotype	protein_coding
OMIM	603205
Entrez	27136

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000232603, ENST00000483760

RefSeq mRNA: 1 — MANE Select: NM_014429 NM_014429

CCDS: CCDS2955

Canonical transcript exons

ENST00000232603 — 28 exons

Exon	Start	End
ENSE00000775170	108963414	108963608
ENSE00000775171	108969669	108969722
ENSE00000775172	108971330	108971402
ENSE00000775173	108979515	108979667
ENSE00000775174	108984716	108984782
ENSE00000775175	108986880	108986949
ENSE00000775177	109000557	109000658
ENSE00000775179	109004817	109004888
ENSE00000775181	109005070	109005315
ENSE00000775183	109007029	109007091
ENSE00000775185	109027751	109027889
ENSE00000775187	109032720	109032825
ENSE00000775189	109035340	109035468
ENSE00000775191	109054728	109054882
ENSE00000775193	109057343	109057486
ENSE00000775194	109059806	109059870
ENSE00000775195	109061988	109062058
ENSE00000775196	109063152	109063231
ENSE00000823413	108958248	108959120
ENSE00000823416	109069632	109069757
ENSE00001200747	109093436	109093541
ENSE00001200753	109094909	109095068
ENSE00001200759	109099358	109099466
ENSE00001200763	109100417	109100507
ENSE00001200766	109103849	109103917
ENSE00001200767	109110749	109110783
ENSE00001200770	109114384	109114437
ENSE00001314208	109117995	109118134

Expression profiles

Bgee: expression breadth broad, 36 present calls, max score 92.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0240 / max 17.5923, expressed in 7 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43685	0.0064	4
43683	0.0061	3
43684	0.0061	4
43682	0.0053	3

Top tissues by expression

271 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.21	gold quality
testis	UBERON:0000473	75.77	gold quality
right testis	UBERON:0004534	75.74	gold quality
left testis	UBERON:0004533	73.65	gold quality
buccal mucosa cell	CL:0002336	59.46	gold quality
lower lobe of lung	UBERON:0008949	52.42	silver quality
left ventricle myocardium	UBERON:0006566	51.29	gold quality
monocyte	CL:0000576	50.18	silver quality
mononuclear cell	CL:0000842	50.18	silver quality
leukocyte	CL:0000738	49.81	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.53	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
myocardium	UBERON:0002349	49.15	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
quadriceps femoris	UBERON:0001377	48.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	6.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting MORC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-452-5P	99.65	69.63	1762

Literature-anchored findings (GeneRIF, showing 4)

• MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. (PMID:25158004)
• The results of this study showed that DNA methylation in the MORC1 promoter region significantly correlates with the Beck Depression Inventory score in the examined non-clinical population. (PMID:29890506)
• Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms. (PMID:31683097)
• MORC1 methylation and BDI are associated with microstructural features of the hippocampus and medial prefrontal cortex. (PMID:33401128)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Morc1	ENSMUSG00000022652
rattus_norvegicus	Morc1	ENSRNOG00000032101
caenorhabditis_elegans		WBGENE00022531

Paralogs (1): MORC2 (ENSG00000133422)

Protein

Protein identifiers

MORC family CW-type zinc finger protein 1 — Q86VD1 (reviewed: Q86VD1)

Alternative names: Cancer/testis antigen 33

All UniProt accessions (1): Q86VD1

UniProt curated annotations — full annotation on UniProt →

Function. Required for spermatogenesis. Essential for de novo DNA methylation and silencing of transposable elements in the male embryonic germ cells.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86VD1-1	1	yes
Q86VD1-2	2

RefSeq proteins (1): NP_055244* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011124	Znf_CW	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR041006	Morc_S5	Domain

Pfam: PF07496, PF13589, PF17942

UniProt features (22 total): sequence variant 10, binding site 4, coiled-coil region 3, sequence conflict 2, chain 1, zinc finger region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VD1-F1	69.88	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 486; 489; 512; 523

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, RNGTGGGC_UNKNOWN, FREAC2_01, GOBP_BEHAVIOR, GOBP_MALE_GAMETE_GENERATION, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_FEAR_RESPONSE, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, HFH1_01, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (10): behavioral fear response (GO:0001662), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), regulatory ncRNA-mediated gene silencing (GO:0031047), retrotransposition (GO:0032197), epigenetic programing of male pronucleus (GO:0044727), transposable element silencing by heterochromatin formation (GO:0141005), negative regulation of DNA-templated transcription initiation (GO:2000143), negative regulation of gene expression (GO:0010629), epigenetic regulation of gene expression (GO:0040029)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): male germ cell nucleus (GO:0001673), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	2
behavioral defense response	1
fear response	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
negative regulation of gene expression	1
transposition	1
epigenetic programming in the zygotic pronuclei	1
transposable element silencing	1
constitutive heterochromatin formation	1
DNA-templated transcription initiation	1
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription initiation	1
gene expression	1
negative regulation of macromolecule biosynthetic process	1
chromatin remodeling	1
transition metal ion binding	1
binding	1
cation binding	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MORC1	MEI1	Q5TIA1	768
MORC1	SPO11	Q9Y5K1	716
MORC1	SMCHD1	A6NHR9	482
MORC1	YIPF2	Q9BWQ6	479
MORC1	HDAC3	O15379	477
MORC1	TDRD9	Q8NDG6	466
MORC1	DNMT3A	Q9Y6K1	452
MORC1	OR3A2	P47893	450
MORC1	RAD51	Q06609	450
MORC1	SLC6A4	P31645	446
MORC1	HAUS3	Q68CZ6	444
MORC1	TEX15	Q9BXT5	434
MORC1	DZIP3	Q86Y13	432
MORC1	TYR	P14679	429
MORC1	MRPS23	Q9Y3D9	427

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DHX8	AHCYL1	psi-mi:“MI:0914”(association)	0.640
MORC1	MORC2	psi-mi:“MI:0915”(physical association)	0.620
MORC1	RNF40	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
DPH6	ATP2B2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): MORC2 (Affinity Capture-MS), RNF40 (Affinity Capture-MS), HERC1 (Affinity Capture-MS), PJA1 (Affinity Capture-MS), MORC2 (Affinity Capture-MS), HERC1 (Affinity Capture-MS), GMEB1 (Affinity Capture-MS), RNF40 (Affinity Capture-MS), MORC1 (Affinity Capture-MS), MORC1 (Affinity Capture-Western), RNF40 (Affinity Capture-MS), GMEB1 (Affinity Capture-MS), MORC1 (Affinity Capture-MS), MORC2 (Affinity Capture-MS), HERC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: F4JPP0, F4JRS4, F4K2G3, F4KAF2, F7BJB9, Q14149, Q56Y74, Q5FV35, Q84WV6, Q86VD1, Q8BMD7, Q8TE76, Q9WVL5, Q8C5W4, Q23243, Q9Y6X9, Q69ZX6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

114 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

6347 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108959116:CCACC:C	acceptor_gain	1.0000
3:108959117:CACC:C	acceptor_gain	1.0000
3:108959117:CACCC:C	acceptor_gain	1.0000
3:108959119:CC:C	acceptor_gain	1.0000
3:108959120:CC:C	acceptor_gain	1.0000
3:108959120:CCTG:C	acceptor_loss	1.0000
3:108959121:CTGG:C	acceptor_loss	1.0000
3:108959122:T:C	acceptor_loss	1.0000
3:108969730:CA:C	acceptor_gain	1.0000
3:108969731:A:AC	acceptor_gain	1.0000
3:108969731:A:C	acceptor_gain	1.0000
3:108969731:A:T	acceptor_gain	1.0000
3:108979679:C:CT	acceptor_gain	1.0000
3:109032834:C:CT	acceptor_gain	1.0000
3:109032835:A:T	acceptor_gain	1.0000
3:109035339:CCA:C	donor_gain	1.0000
3:109035439:CAT:C	acceptor_gain	1.0000
3:109035441:T:C	acceptor_gain	1.0000
3:109035441:T:TC	acceptor_gain	1.0000
3:109035470:T:C	acceptor_gain	1.0000
3:109035472:T:C	acceptor_gain	1.0000
3:109054726:A:AC	donor_gain	1.0000
3:109054727:C:CC	donor_gain	1.0000
3:109055205:A:AC	donor_gain	1.0000
3:109055206:C:CC	donor_gain	1.0000
3:109056864:C:CT	acceptor_gain	1.0000
3:109057341:A:AC	donor_gain	1.0000
3:109057342:C:CC	donor_gain	1.0000
3:109057497:A:C	acceptor_gain	1.0000
3:109057499:T:C	acceptor_gain	1.0000

AlphaMissense

6529 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:109054817:T:A	K414I	0.993
3:109099392:G:A	S130F	0.993
3:109099382:G:C	F133L	0.992
3:109099382:G:T	F133L	0.992
3:109099384:A:G	F133L	0.992
3:109095061:A:T	V144D	0.991
3:109099383:A:G	F133S	0.991
3:109099444:C:G	D113H	0.991
3:109099393:A:G	S130P	0.990
3:109099392:G:T	S130Y	0.989
3:109099466:A:C	S105R	0.989
3:109099466:A:T	S105R	0.989
3:109100418:T:G	S105R	0.989
3:109054807:A:C	F417L	0.988
3:109054807:A:T	F417L	0.988
3:109054809:A:G	F417L	0.988
3:109099449:C:T	G111E	0.988
3:109057394:C:G	R375P	0.987
3:109094969:A:G	S175P	0.986
3:109100419:T:A	K104N	0.985
3:109100419:T:G	K104N	0.985
3:109093487:A:G	L213S	0.984
3:109054808:A:G	F417S	0.983
3:109054816:T:A	K414N	0.983
3:109054816:T:G	K414N	0.983
3:109099431:A:G	F117S	0.983
3:109099443:T:G	D113A	0.983
3:109093464:C:G	D221H	0.981
3:109099449:C:A	G111V	0.981
3:109057391:A:G	L376S	0.980

dbSNP variants (sampled 300 via entrez): RS1000006707 (3:108971897 G>A,T), RS1000020163 (3:109012808 A>G), RS1000038007 (3:109054795 T>C,G), RS1000055954 (3:109011046 G>A), RS1000071325 (3:109100623 G>A), RS1000072619 (3:109004061 T>C), RS1000098824 (3:109100843 T>C), RS1000103948 (3:109097010 T>C,G), RS1000173780 (3:109039654 C>T), RS1000178427 (3:109032918 T>C), RS1000189598 (3:109111893 T>G), RS1000197514 (3:108977655 G>A), RS1000218178 (3:109030810 T>A,C), RS1000232203 (3:109020015 A>C), RS1000238378 (3:109072941 A>G)

Disease associations

OMIM: gene MIM:603205 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002251_4	Homeostasis model assessment of beta-cell function (dietary factor interaction)	3.000000e-07
GCST002415_5	Colorectal cancer (diet interaction)	2.000000e-06
GCST002415_7	Colorectal cancer (diet interaction)	2.000000e-06
GCST003225_27	Pelvic organ prolapse (moderate/severe)	6.000000e-07
GCST010241_33	Apolipoprotein A1 levels	1.000000e-16
GCST010242_220	HDL cholesterol levels	8.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004469	HOMA-B
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation	2
bisphenol A	affects cotreatment, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.