MITD1

Summary

MITD1 (microtubule interacting and trafficking domain containing 1, HGNC:25207) is a protein-coding gene on chromosome 2q11.2, encoding MIT domain-containing protein 1 (Q8WV92). Required for efficient abscission at the end of cytokinesis, together with components of the ESCRT-III complex.

Abscission, the separation of daughter cells at the end of cytokinesis, is effected by endosomal sorting complexes required for transport III (ESCRT-III). The protein encoded by this gene functions as a homodimer, with the N-termini binding to a subset of ESCRT-III subunits and the C-termini binding to membranes. The encoded protein regulates ESCRT-III activity and is required for proper cytokinesis. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 129531 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_138798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25207
Approved symbol	MITD1
Name	microtubule interacting and trafficking domain containing 1
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	LOC129531
Ensembl gene	ENSG00000158411
Ensembl biotype	protein_coding
Entrez	129531

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 3 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000289359, ENST00000409107, ENST00000413710, ENST00000422537, ENST00000438121, ENST00000464685, ENST00000466880, ENST00000483721, ENST00000487588

RefSeq mRNA: 4 — MANE Select: NM_138798 NM_001320417, NM_001320418, NM_001320419, NM_138798

CCDS: CCDS2040

Canonical transcript exons

ENST00000289359 — 7 exons

Exon	Start	End
ENSE00001164376	99169263	99169470
ENSE00001164384	99180831	99181058
ENSE00003474402	99169550	99169610
ENSE00003527482	99170537	99170652
ENSE00003580802	99171343	99171429
ENSE00003580886	99171510	99171646
ENSE00003704182	99173915	99174016

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 96.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.6291 / max 531.8351, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29878	26.5066	1803
29877	7.1225	1657

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.04	gold quality
monocyte	CL:0000576	95.21	gold quality
vermiform appendix	UBERON:0001154	94.98	gold quality
leukocyte	CL:0000738	94.93	gold quality
spleen	UBERON:0002106	94.69	gold quality
granulocyte	CL:0000094	94.36	gold quality
lymph node	UBERON:0000029	94.10	gold quality
lower esophagus mucosa	UBERON:0035834	94.01	gold quality
metanephros cortex	UBERON:0010533	93.22	gold quality
right uterine tube	UBERON:0001302	93.14	gold quality
rectum	UBERON:0001052	93.13	gold quality
endocervix	UBERON:0000458	92.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.57	gold quality
body of uterus	UBERON:0009853	92.46	gold quality
left lobe of thyroid gland	UBERON:0001120	92.29	gold quality
oocyte	CL:0000023	92.28	gold quality
right ovary	UBERON:0002118	92.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.23	gold quality
right lobe of thyroid gland	UBERON:0001119	92.14	gold quality
tibial nerve	UBERON:0001323	92.08	gold quality
right adrenal gland	UBERON:0001233	91.88	gold quality
left ovary	UBERON:0002119	91.86	gold quality
ectocervix	UBERON:0012249	91.73	gold quality
right adrenal gland cortex	UBERON:0035827	91.69	gold quality
smooth muscle tissue	UBERON:0001135	91.67	gold quality
transverse colon	UBERON:0001157	91.60	gold quality
mucosa of transverse colon	UBERON:0004991	91.59	gold quality
right coronary artery	UBERON:0001625	91.53	gold quality
thyroid gland	UBERON:0002046	91.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting MITD1, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-4760-3P	99.93	70.50	2385

Literature-anchored findings (GeneRIF, showing 7)

• MITD1 participates in the abscission phase of cytokinesis and ESCRT-III subunits are important for the recruitment of MITD1 to the midbody. (PMID:23015756)
• results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division (PMID:23045692)
• Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer. (PMID:33200223)
• Prognostic Impact of MITD1 and Associates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma. (PMID:34346239)
• MITD1 Deficiency Suppresses Clear Cell Renal Cell Carcinoma Growth and Migration by Inducing Ferroptosis through the TAZ/SLC7A11 Pathway. (PMID:36046690)
• Pan-Cancer Analysis of the Prognostic and Immunotherapeutic Value of MITD1. (PMID:36291174)
• Microtubule interacting and trafficking domain containing 1 deficiency leads to poor survival via tissue factor-mediated coagulation in bladder cancer. (PMID:38554936)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mitd1	ENSDARG00000044766
mus_musculus	Mitd1	ENSMUSG00000026088
rattus_norvegicus	Mitd1	ENSRNOG00000018467
drosophila_melanogaster	CG14985	FBGN0035482
drosophila_melanogaster	CG30398	FBGN0050398
caenorhabditis_elegans		WBGENE00013436

Protein

Protein identifiers

MIT domain-containing protein 1 — Q8WV92 (reviewed: Q8WV92)

All UniProt accessions (5): A0A1W2PP14, B8ZZL5, Q8WV92, F8WED5, H7C3Q6

UniProt curated annotations — full annotation on UniProt →

Function. Required for efficient abscission at the end of cytokinesis, together with components of the ESCRT-III complex.

Subunit / interactions. Homodimer. Interacts (via MIT domain) with CHMP1A, CHMP1B, CHMP2A and IST1.

Subcellular location. Late endosome membrane. Midbody. Membrane.

Domain organisation. The C-terminal domain interacts with lipid membranes containing acidic phosphoinositides and is required for location at the midbody. The MIT domain interacts with the MIT-interacting motifs of several components of the ESCRT-III complex.

RefSeq proteins (4): NP_001307346, NP_001307347, NP_001307348, NP_620153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007330	MIT_dom	Domain
IPR032341	MITD1_C	Domain
IPR036181	MIT_dom_sf	Homologous_superfamily
IPR038113	MITD1_C_sf	Homologous_superfamily
IPR045331	MITD1_N	Domain
IPR052817	MIT_domain_contain_protein1	Family

Pfam: PF04212, PF16565

UniProt features (29 total): mutagenesis site 8, helix 8, strand 7, sequence conflict 2, chain 1, domain 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4A5X	X-RAY DIFFRACTION	1.91
4A5Z	X-RAY DIFFRACTION	2.3
2YMB	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WV92-F1	92.09	0.85

Functional residue map

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

Mutagenesis-validated functional residues (8):

Position	Phenotype
231	strongly reduces binding to membranes; when associated with e-221 and e-220.
69	abolishes interaction with chmp1a, chmp1b and chmp2a.
73	abolishes interaction with chmp1a, chmp1b and chmp2a. abolishes location at the midbody.
132	abolishes homodimerization; when associated with a-221 and a-225.
168	strongly reduces binding to membranes; when associated with e-221 and e-231.
220	strongly reduces binding to membranes; when associated with e-168 and e-231.
221	abolishes homodimerization; when associated with a-132 and a-225.
225	abolishes homodimerization; when associated with a-132 and a-221.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): GOBP_MITOTIC_CYTOKINESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CYTOKINETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_BINDING, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_CYTOKINESIS, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_MULTIVESICULAR_BODY_SORTING_PATHWAY, GOBP_VIRAL_LIFE_CYCLE, GOBP_MITOTIC_CELL_CYCLE, GOBP_VIRION_ASSEMBLY, GOBP_MEMBRANE_ORGANIZATION, GOBP_CYTOSKELETON_DEPENDENT_CYTOKINESIS

GO Biological Process (4): mitotic cytokinesis (GO:0000281), negative regulation of protein binding (GO:0032091), midbody abscission (GO:0061952), cell division (GO:0051301)

GO Molecular Function (4): protein domain specific binding (GO:0019904), phosphatidylinositol binding (GO:0035091), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): membrane (GO:0016020), midbody (GO:0030496), late endosome membrane (GO:0031902), extracellular exosome (GO:0070062), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
cellular anatomical structure	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
regulation of protein binding	1
negative regulation of binding	1
membrane organization	1
mitotic cytokinetic process	1
cellular process	1
anion binding	1
binding	1
late endosome	1
endosome membrane	1
extracellular vesicle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MITD1	CHMP2A	O43633	876
MITD1	CHMP1A	Q9HD42	797
MITD1	IST1	P53990	740
MITD1	VPS4A	Q9UN37	737
MITD1	CHMP3	Q9Y3E7	724
MITD1	A0A140T963	A0A140T963	724
MITD1	ENTPD2	Q9Y5L3	668
MITD1	VPS4B	O75351	667
MITD1	GNL1	P36915	540
MITD1	TBCEL	Q5QJ74	514
MITD1	CEP55	Q53EZ4	496
MITD1	RILPL2	Q969X0	471
MITD1	SPAST	Q9UBP0	470
MITD1	ERAL1	O75616	467
MITD1	CHMP1B	Q7LBR1	447

IntAct

104 interactions, top by confidence:

A	B	Type	Score
MITD1	CHMP2A	psi-mi:“MI:0915”(physical association)	0.730
CHMP2A	MITD1	psi-mi:“MI:0403”(colocalization)	0.730
CHMP2A	MITD1	psi-mi:“MI:0915”(physical association)	0.730
ZFYVE19	MITD1	psi-mi:“MI:0915”(physical association)	0.720
MITD1	ZFYVE19	psi-mi:“MI:0915”(physical association)	0.720
MITD1	ZFYVE19	psi-mi:“MI:0915”(physical association)	0.560
MITD1	CHMP5	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE19	MITD1	psi-mi:“MI:0915”(physical association)	0.560
CHMP5	MITD1	psi-mi:“MI:0915”(physical association)	0.560
PTC1	MITD1	psi-mi:“MI:0915”(physical association)	0.560
MITD1	PTC1	psi-mi:“MI:0915”(physical association)	0.560
KANK2	MITD1	psi-mi:“MI:0915”(physical association)	0.560
MITD1	GPHN	psi-mi:“MI:0915”(physical association)	0.560
RTN3	MITD1	psi-mi:“MI:0915”(physical association)	0.560
CHMP1B	MITD1	psi-mi:“MI:0915”(physical association)	0.560
MITD1	MITD1	psi-mi:“MI:0915”(physical association)	0.560
MITD1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
MITD1	CHMP1A	psi-mi:“MI:0915”(physical association)	0.560
ZNF655	MITD1	psi-mi:“MI:0915”(physical association)	0.560
MITD1	CARD10	psi-mi:“MI:0915”(physical association)	0.560
TTC33	MITD1	psi-mi:“MI:0915”(physical association)	0.560
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530

BioGRID (53): MITD1 (Two-hybrid), MITD1 (Two-hybrid), MITD1 (Co-fractionation), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS), MITD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A1Z3X3, A4GWN3, A5PK39, E9Q4Z2, O00763, O55236, O60733, O60942, P10687, P10894, P29144, P49754, P82922, P97570, P97789, P97819, Q15147, Q2KJA6, Q32PW3, Q5IH13, Q5KU39, Q5R8R4, Q5ZKK2, Q640G7, Q641K1, Q64514, Q64560, Q69YN2, Q6NY98, Q6NYU2, Q7ZVK4, Q80YV4, Q8BPM2, Q8CI33, Q8IVH8, Q8IZH2, Q8K114, Q8QFR2

Diamond homologs: P52917, Q09803, Q5I0J5, Q8VDV8, Q8WV92

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Neutrophil degranulation	10	4.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	5	76.2×	2e-07
late endosome to lysosome transport	5	76.2×	2e-07
viral budding via host ESCRT complex	6	74.1×	5e-08
midbody abscission	6	67.6×	5e-08
multivesicular body sorting pathway	5	61.7×	5e-07
regulation of centrosome duplication	5	56.4×	8e-07
regulation of mitotic spindle assembly	5	56.4×	8e-07
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	6	50.2×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1059 predictions. Top by Δscore:

Variant	Effect	Δscore
2:99169611:C:CC	acceptor_gain	1.0000
2:99170532:CTAA:C	donor_loss	1.0000
2:99170533:TAA:T	donor_loss	1.0000
2:99170534:AAC:A	donor_loss	1.0000
2:99170535:A:AC	donor_gain	1.0000
2:99170535:ACC:A	donor_loss	1.0000
2:99170536:C:CC	donor_gain	1.0000
2:99170576:T:TA	donor_gain	1.0000
2:99170648:ATGCC:A	acceptor_gain	1.0000
2:99170649:TGCC:T	acceptor_gain	1.0000
2:99170650:GCC:G	acceptor_gain	1.0000
2:99170651:CC:C	acceptor_gain	1.0000
2:99170651:CCC:C	acceptor_gain	1.0000
2:99170652:CC:C	acceptor_gain	1.0000
2:99170652:CCTGT:C	acceptor_loss	1.0000
2:99170653:C:CA	acceptor_loss	1.0000
2:99170653:C:CC	acceptor_gain	1.0000
2:99171341:A:AC	donor_gain	1.0000
2:99171342:C:CC	donor_gain	1.0000
2:99171425:TACAG:T	acceptor_gain	1.0000
2:99171427:CAG:C	acceptor_gain	1.0000
2:99171505:CATA:C	donor_loss	1.0000
2:99171506:ATAC:A	donor_loss	1.0000
2:99171507:TA:T	donor_loss	1.0000
2:99171508:A:AG	donor_loss	1.0000
2:99171647:C:CC	acceptor_gain	1.0000
2:99174013:GTACC:G	acceptor_loss	1.0000
2:99174016:CCT:C	acceptor_loss	1.0000
2:99174017:CTACA:C	acceptor_loss	1.0000
2:99174018:T:A	acceptor_loss	1.0000

AlphaMissense

1645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:99170546:C:G	R195P	0.996
2:99169432:T:A	R231S	0.993
2:99169432:T:G	R231S	0.993
2:99169575:C:T	G210E	0.993
2:99169577:C:A	R209S	0.993
2:99169577:C:G	R209S	0.993
2:99171362:A:G	L153P	0.993
2:99169578:C:G	R209T	0.992
2:99169426:A:C	C233W	0.991
2:99169576:C:G	G210R	0.991
2:99169576:C:T	G210R	0.991
2:99169412:A:T	V238E	0.990
2:99169597:A:G	W203R	0.989
2:99169597:A:T	W203R	0.989
2:99171536:C:G	D122H	0.989
2:99171547:A:T	V118D	0.989
2:99171594:A:C	S102R	0.989
2:99171594:A:T	S102R	0.989
2:99171596:T:G	S102R	0.989
2:99180861:C:G	G41R	0.989
2:99180861:C:T	G41R	0.989
2:99169433:C:G	R231T	0.988
2:99170600:A:G	L177P	0.988
2:99171408:A:G	C138R	0.988
2:99173954:C:G	A72P	0.988
2:99169427:C:T	C233Y	0.987
2:99169434:T:C	R231G	0.987
2:99169578:C:A	R209M	0.987
2:99180882:C:G	A34P	0.985
2:99169572:A:T	L211H	0.984

dbSNP variants (sampled 300 via entrez): RS1000186375 (2:99162464 C>T), RS1000206874 (2:99169851 A>G), RS1000220232 (2:99176887 C>A,T), RS1000239362 (2:99169544 T>A,C), RS1000244744 (2:99173745 A>C), RS1000373733 (2:99183024 C>G), RS1000392886 (2:99166915 C>G), RS1000484305 (2:99163341 T>C), RS1000540689 (2:99168112 A>G), RS1000611261 (2:99167890 C>T), RS1000660028 (2:99181910 T>A,C), RS1000676661 (2:99168015 C>T), RS1000713355 (2:99181405 C>G), RS1001169906 (2:99175342 C>T), RS1001567564 (2:99179427 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616299

GenCC curated gene-disease

Mondo (1): lipoyl transferase 1 deficiency (MONDO:0014576)

Orphanet (1): Lipoyl transferase 1 deficiency (Orphanet:401862)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001241_13	Bipolar disorder	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylparaben	increases expression	1
sodium arsenite	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
MT19c compound	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Ethanol	decreases expression, increases abundance, affects cotreatment	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	increases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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