MTCL2

Summary

MTCL2 (microtubule crosslinking factor 2, HGNC:16111) is a protein-coding gene on chromosome 20q11.23, encoding Microtubule cross-linking factor 2 (O94964). Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration.

Involved in chromosome segregation. Located in extracellular space; microtubule; and midbody.

Source: NCBI Gene 140710 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 251 total
• MANE Select transcript: NM_080627

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16111
Approved symbol	MTCL2
Name	microtubule crosslinking factor 2
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	dJ132F21.1, FLJ44670, SOGA
Ensembl gene	ENSG00000149639
Ensembl biotype	protein_coding
OMIM	620225
Entrez	140710

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000237536, ENST00000279034, ENST00000463491, ENST00000465671, ENST00000938705

RefSeq mRNA: 2 — MANE Select: NM_080627 NM_080627, NM_199181

CCDS: CCDS46598, CCDS54459

Canonical transcript exons

ENST00000237536 — 15 exons

Exon	Start	End
ENSE00000800452	36862658	36863538
ENSE00001401857	36793249	36794599
ENSE00001461378	36777447	36786637
ENSE00002997757	36796882	36796952
ENSE00003001509	36817407	36817469
ENSE00003021883	36804735	36804902
ENSE00003022731	36829054	36829212
ENSE00003046992	36815126	36816307
ENSE00003057391	36812704	36812844
ENSE00003061605	36809982	36810107
ENSE00003118562	36797502	36797573
ENSE00003131464	36802856	36803107
ENSE00003140549	36808513	36808743
ENSE00003216242	36805853	36805957
ENSE00003550310	36839217	36839441

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 94.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0714 / max 213.3838, expressed in 1718 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187149	5.2634	1591
187151	2.1638	1139
187152	0.8539	441
187150	0.7249	441
187144	0.0655	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellum	UBERON:0002037	94.66	gold quality
cerebellar cortex	UBERON:0002129	94.53	gold quality
cerebellar hemisphere	UBERON:0002245	94.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.02	gold quality
left ventricle myocardium	UBERON:0006566	92.05	silver quality
cortical plate	UBERON:0005343	91.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.55	silver quality
sural nerve	UBERON:0015488	91.38	gold quality
ganglionic eminence	UBERON:0004023	90.79	gold quality
cerebellar vermis	UBERON:0004720	88.66	gold quality
lower lobe of lung	UBERON:0008949	87.78	gold quality
kidney epithelium	UBERON:0004819	87.74	silver quality
ventricular zone	UBERON:0003053	86.75	gold quality
upper arm skin	UBERON:0004263	86.58	silver quality
corpus callosum	UBERON:0002336	85.94	gold quality
inferior vagus X ganglion	UBERON:0005363	84.15	gold quality
adrenal tissue	UBERON:0018303	83.99	gold quality
stromal cell of endometrium	CL:0002255	83.70	gold quality
saphenous vein	UBERON:0007318	83.60	gold quality
superficial temporal artery	UBERON:0001614	83.39	gold quality
right adrenal gland cortex	UBERON:0035827	82.70	gold quality
right coronary artery	UBERON:0001625	82.68	gold quality
adrenal cortex	UBERON:0001235	82.48	gold quality
adrenal gland	UBERON:0002369	82.38	gold quality
right adrenal gland	UBERON:0001233	82.33	gold quality
subthalamic nucleus	UBERON:0001906	82.26	gold quality
left adrenal gland cortex	UBERON:0035825	82.26	gold quality
postcentral gyrus	UBERON:0002581	82.23	gold quality
ventral tegmental area	UBERON:0002691	81.86	gold quality
left adrenal gland	UBERON:0001234	81.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting MTCL2, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216

Literature-anchored findings (GeneRIF, showing 3)

• Authors selected an HCC-specific RNA-based biomarker panel that depended on the integration of suppressor of glucose autophagy-associated (SOGA1) gene expression with the chosen panel of epigenetic regulators of this gene [long non-coding RNA antisense for X-inactive-specific transcript (lncRNA-TSIX) and microRNA-548-a-3p (miR-548-a-3p)]. (PMID:31004302)
• SOGA1 and SOGA2/MTCL1 are CLASP-interacting proteins required for faithful chromosome segregation in human cells. (PMID:33587225)
• METTL16-mediated N6-methyladenosine modification of Soga1 enables proper chromosome segregation and chromosomal stability in colorectal cancer. (PMID:38084791)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtcl2	ENSDARG00000063075
danio_rerio	mtcl3a	ENSDARG00000088571
mus_musculus	Mtcl2	ENSMUSG00000055485
rattus_norvegicus	Mtcl2	ENSRNOG00000053240

Paralogs (2): MTCL1 (ENSG00000168502), MTCL3 (ENSG00000214338)

Protein

Protein identifiers

Microtubule cross-linking factor 2 — O94964 (reviewed: O94964)

Alternative names: SOGA family member 1, Suppressor of glucose by autophagy, Suppressor of glucose, autophagy-associated protein 1

All UniProt accessions (3): O94964, H0YDM2, X6R3R3

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Preferentially acts on the perinuclear microtubules accumulated around the Golgi. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain. Required for faithful chromosome segregation during mitosis. Regulates autophagy by playing a role in the reduction of glucose production in an adiponectin- and insulin-dependent manner.

Subunit / interactions. Interacts with CLASP1 and CLASP2. The C-terminal 25 kDa form occurs as a monomer.

Subcellular location. Cytoplasm. Cytoskeleton. Golgi apparatus membrane. Midbody Secreted.

Post-translational modifications. Proteolytically cleaved in primary hepatocytes into a C-terminal 80 kDa form. Proteolytically cleaved into a C-terminal SOGA 25 kDa form that is detected in plasma. Phosphorylated during mitosis in a CDK1-dependent manner.

Domain organisation. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain.

Induction. Up-regulated in the plasma by adiponectin in healthy fasting female.

Similarity. Belongs to the MTCL family.

Isoforms (4)

UniProt ID	Names	Canonical?
O94964-2	1	yes
O94964-1	2
O94964-3	3
O94964-4	4

RefSeq proteins (2): NP_542194, NP_954650 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027881	SOGA_CC	Domain
IPR027882	SOGA1/2-like_CC	Domain
IPR049885	MTCL1-3	Family

Pfam: PF11365, PF14818

UniProt features (29 total): region of interest 7, coiled-coil region 5, compositionally biased region 5, splice variant 5, chain 3, modified residue 2, site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94964-F1	55.80	0.20

Functional residue map

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

Catalytic / active sites (1): 926–927 (cleavage)

Post-translational modifications (2): 1169, 1255

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 347 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, CACCAGC_MIR138, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_INSULIN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, ACATTCC_MIR1_MIR206

GO Biological Process (5): chromosome segregation (GO:0007059), insulin receptor signaling pathway (GO:0008286), regulation of autophagy (GO:0010506), negative regulation of gluconeogenesis (GO:0045721), cell division (GO:0051301)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), microtubule (GO:0005874), midbody (GO:0030496), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell cycle process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
autophagy	1
regulation of catabolic process	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
cellular process	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
extracellular vesicle	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTCL2	GPR155	Q7Z3F1	519
MTCL2	TTC29	Q8NA56	519
MTCL2	ITFG1	Q8TB96	442
MTCL2	MROH8	Q9H579	390
MTCL2	MEF2D	Q14814	361
MTCL2	PHIP	Q8WWQ0	360
MTCL2	OGA	O60502	358
MTCL2	SCYL2	Q6P3W7	345
MTCL2	GDPGP1	Q6ZNW5	337
MTCL2	WDFY3	Q8IZQ1	334
MTCL2	DRAM1	Q8N682	333
MTCL2	STXBP4	Q6ZWJ1	327
MTCL2	XIRP2	A4UGR9	322
MTCL2	PCDH15	Q96QU1	322
MTCL2	CDH23	Q9H251	320

IntAct

74 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
PPP2R5A	AXIN1	psi-mi:“MI:0914”(association)	0.530
ZNF263	AHCYL1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
SGO1	USP12	psi-mi:“MI:0914”(association)	0.530
MTCL2	JPH2	psi-mi:“MI:0915”(physical association)	0.400
SLC25A25	MTCL2	psi-mi:“MI:0915”(physical association)	0.400
PRKAA1	MTCL2	psi-mi:“MI:0915”(physical association)	0.400
PRKAB1	MTCL2	psi-mi:“MI:0915”(physical association)	0.400
PRKAG1	MTCL2	psi-mi:“MI:0915”(physical association)	0.400
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Cul4a	GPS1	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
E6	TRAFD1	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350

BioGRID (155): SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

Diamond homologs: E1U8D0, O94964, Q3UHU5, Q5TF21, Q6NZL0, Q9Y4B5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	88.8×	1e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	78.4×	1e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	78.4×	1e-10
Activation of BH3-only proteins	7	57.9×	9e-10
RHO GTPases activate PKNs	8	42.3×	6e-10
Intrinsic Pathway for Apoptosis	7	34.2×	3e-08
RAF activation	6	33.6×	4e-07
FOXO-mediated transcription	5	28.0×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	22.3×	5e-04
substantia nigra development	5	22.3×	5e-04
intracellular protein localization	8	10.2×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	211
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2346 predictions. Top by Δscore:

Variant	Effect	Δscore
20:36796881:CCT:C	donor_gain	1.0000
20:36796896:T:TA	donor_gain	1.0000
20:36796909:A:C	donor_gain	1.0000
20:36796948:CGTGT:C	acceptor_gain	1.0000
20:36796950:TGT:T	acceptor_gain	1.0000
20:36796951:GT:G	acceptor_gain	1.0000
20:36796952:TCT:T	acceptor_loss	1.0000
20:36796953:C:A	acceptor_loss	1.0000
20:36796953:C:CC	acceptor_gain	1.0000
20:36796954:T:A	acceptor_loss	1.0000
20:36797497:CTCA:C	donor_loss	1.0000
20:36797499:CA:C	donor_loss	1.0000
20:36797500:ACCT:A	donor_gain	1.0000
20:36797501:CCT:C	donor_gain	1.0000
20:36797501:CCTC:C	donor_gain	1.0000
20:36797503:T:TA	donor_gain	1.0000
20:36797574:C:CC	acceptor_gain	1.0000
20:36802850:CCTCA:C	donor_loss	1.0000
20:36802852:TCACC:T	donor_loss	1.0000
20:36802853:CA:C	donor_loss	1.0000
20:36802854:ACCT:A	donor_loss	1.0000
20:36802855:C:G	donor_loss	1.0000
20:36802855:CCTGG:C	donor_gain	1.0000
20:36804730:CTCA:C	donor_loss	1.0000
20:36804731:TCA:T	donor_loss	1.0000
20:36804732:CA:C	donor_loss	1.0000
20:36804733:A:AC	donor_gain	1.0000
20:36804734:C:CC	donor_gain	1.0000
20:36804734:C:T	donor_loss	1.0000
20:36804898:TTGGG:T	acceptor_gain	1.0000

AlphaMissense

10765 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012996 (20:36781112 A>C), RS1000018826 (20:36838501 G>A), RS1000079053 (20:36786076 G>A), RS1000126185 (20:36799469 G>A), RS1000130704 (20:36854638 G>C), RS1000162147 (20:36799841 A>G), RS1000211343 (20:36821347 C>T), RS1000269604 (20:36831933 C>T), RS1000276654 (20:36821631 T>A,C), RS1000333058 (20:36806211 A>G), RS1000386967 (20:36814581 T>C), RS1000421902 (20:36792685 T>C), RS1000434864 (20:36801650 A>G), RS1000444963 (20:36807962 G>A), RS1000497674 (20:36865410 A>T)

Disease associations

OMIM: gene MIM:620225 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002794_12	Airway wall thickness	8.000000e-06
GCST010002_66	Refractive error	2.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006898	airway wall thickness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	increases abundance, affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	decreases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
2-butenal	decreases expression	1
arsenite	affects binding, decreases reaction	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Ethanol	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Estradiol	increases expression	1
Smoke	decreases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vitamin E	decreases expression	1
Asbestos, Serpentine	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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