MINDY2

Summary

MINDY2 (MINDY lysine 48 deubiquitinase 2, HGNC:26954) is a protein-coding gene on chromosome 15q21.3-q22.1, encoding Ubiquitin carboxyl-terminal hydrolase MINDY-2 (Q8NBR6). Hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins.

Enables peptidase activity and polyubiquitin modification-dependent protein binding activity. Predicted to be involved in chromatin remodeling and proteolysis. Located in nucleoplasm.

Source: NCBI Gene 54629 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_001040450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26954
Approved symbol	MINDY2
Name	MINDY lysine 48 deubiquitinase 2
Location	15q21.3-q22.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1164
Ensembl gene	ENSG00000128923
Ensembl biotype	protein_coding
OMIM	618408
Entrez	54629

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000316848, ENST00000450403, ENST00000559228, ENST00000559745, ENST00000560289, ENST00000877340, ENST00000877341, ENST00000877342, ENST00000877343, ENST00000877344, ENST00000877345, ENST00000877346, ENST00000877347, ENST00000933140, ENST00000933141, ENST00000963691, ENST00000963692, ENST00000963693

RefSeq mRNA: 2 — MANE Select: NM_001040450 NM_001040450, NM_001040453

CCDS: CCDS42046, CCDS45268

Canonical transcript exons

ENST00000559228 — 9 exons

Exon	Start	End
ENSE00000931475	58787906	58787963
ENSE00002545617	58771302	58772235
ENSE00002564963	58854482	58861900
ENSE00003501469	58851771	58851965
ENSE00003571422	58847297	58847470
ENSE00003627687	58831774	58831916
ENSE00003734241	58802313	58802377
ENSE00003742119	58810230	58810388
ENSE00003747916	58821717	58821819

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8188 / max 266.2477, expressed in 1794 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146952	14.2435	1781
146949	1.5831	890
146951	1.0703	712
146950	0.7422	400
146948	0.1797	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trigeminal ganglion	UBERON:0001675	96.64	gold quality
saphenous vein	UBERON:0007318	95.64	gold quality
pons	UBERON:0000988	94.70	gold quality
superior vestibular nucleus	UBERON:0007227	93.20	gold quality
pericardium	UBERON:0002407	92.52	gold quality
dorsal root ganglion	UBERON:0000044	92.19	gold quality
inferior vagus X ganglion	UBERON:0005363	91.77	gold quality
subthalamic nucleus	UBERON:0001906	91.72	gold quality
renal medulla	UBERON:0000362	90.98	gold quality
superior surface of tongue	UBERON:0007371	90.50	gold quality
vena cava	UBERON:0004087	90.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.90	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.61	gold quality
substantia nigra pars compacta	UBERON:0001965	89.35	gold quality
urethra	UBERON:0000057	89.14	gold quality
sural nerve	UBERON:0015488	89.14	gold quality
synovial joint	UBERON:0002217	89.09	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.87	gold quality
germinal epithelium of ovary	UBERON:0001304	88.81	gold quality
calcaneal tendon	UBERON:0003701	88.74	gold quality
cerebellar vermis	UBERON:0004720	88.51	gold quality
ventricular zone	UBERON:0003053	88.39	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.36	gold quality
pigmented layer of retina	UBERON:0001782	88.30	gold quality
placenta	UBERON:0001987	88.12	gold quality
blood vessel layer	UBERON:0004797	87.95	gold quality
left ventricle myocardium	UBERON:0006566	87.95	gold quality
parietal lobe	UBERON:0001872	87.93	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.70	gold quality
ventral tegmental area	UBERON:0002691	87.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.45

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Results identified FAM63B hypomethylation in bipolar disorder patients and data support that FAM63B is a shared epigenetic risk gene for bipolar disorder and schizophrenia. (PMID:27175219)
• Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2. (PMID:34529927)
• Exosomal circFAM63Bsuppresses bone regeneration of postmenopausal osteoporosis via regulating miR-578/HMGA2 axis. (PMID:38151824)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mindy2	ENSDARG00000017431
mus_musculus	Mindy2	ENSMUSG00000042444
rattus_norvegicus	Mindy2	ENSRNOG00000061337
caenorhabditis_elegans		WBGENE00021926

Paralogs (1): MINDY1 (ENSG00000143409)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase MINDY-2 — Q8NBR6 (reviewed: Q8NBR6)

Alternative names: Deubiquitinating enzyme MINDY-2, Protein FAM63B

All UniProt accessions (3): Q8NBR6, H0YM15, J3KNL7

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins. Binds to polyubiquitin chains of different linkage types, including ‘Lys-6’, ‘Lys-11’, ‘Lys-29’, ‘Lys-33’, ‘Lys-48’ and ‘Lys-63’. May play a regulatory role at the level of protein turnover.

Similarity. Belongs to the MINDY deubiquitinase family. FAM63 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBR6-1	1	yes
Q8NBR6-2	2

RefSeq proteins (2): NP_001035540, NP_001035543 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007518	MINDY	Family
IPR033979	MINDY_domain	Domain

Pfam: PF04424

UniProt features (40 total): strand 11, helix 11, region of interest 4, site 3, compositionally biased region 3, mutagenesis site 2, active site 2, chain 1, modified residue 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6Z49	X-RAY DIFFRACTION	2
6Z7V	X-RAY DIFFRACTION	2.65
7NPI	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBR6-F1	65.02	0.28

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 (5): 542 (ubiquitin-binding); 545–546 (ubiquitin-binding); 549 (ubiquitin-binding); 266 (nucleophile); 448 (proton acceptor)

Post-translational modifications (1): 94

Mutagenesis-validated functional residues (2):

Position	Phenotype
519	strongly decreased binding to ’lys-48’ or ’lys-63’-tetraubiquitin chains.
546	no effect on binding to ’lys-48’- or ’lys-63’-tetraubiquitin chains.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 332 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, MORF_RAD51L3, MORF_CTSB, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, MORF_IL4, MORF_PRKCA, BASAKI_YBX1_TARGETS_DN, CUI_TCF21_TARGETS_2_DN, MORF_ATF2, ZHAN_MULTIPLE_MYELOMA_CD1_DN, XU_GH1_EXOGENOUS_TARGETS_DN, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, LEE_RECENT_THYMIC_EMIGRANT, GOBP_PROTEOLYSIS, OSF2_Q6

GO Biological Process (2): proteolysis (GO:0006508), chromatin remodeling (GO:0006338)

GO Molecular Function (11): cysteine-type deubiquitinase activity (GO:0004843), cysteine-type carboxypeptidase activity (GO:0016807), K48-linked polyubiquitin modification-dependent protein binding (GO:0036435), K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), K11-linked polyubiquitin modification-dependent protein binding (GO:0071795), K6-linked polyubiquitin modification-dependent protein binding (GO:0071796), K48-linked deubiquitinase activity (GO:1990380), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), histone deubiquitinase activity (GO:0140934)

GO Cellular Component (2): nucleoplasm (GO:0005654), cell periphery (GO:0071944)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
polyubiquitin modification-dependent protein binding	4
deubiquitinase activity	3
cellular anatomical structure	2
protein metabolic process	1
chromatin organization	1
cysteine-type peptidase activity	1
carboxypeptidase activity	1
cysteine-type exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
histone modifying activity	1
nuclear lumen	1

Protein interactions and networks

STRING

648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MINDY2	MINDY3	Q9H8M7	547
MINDY2	MINDY4	Q4G0A6	545
MINDY2	KLC1	Q07866	518
MINDY2	LTN1	O94822	455
MINDY2	TRMO	Q9BU70	388
MINDY2	SSH2	Q76I76	384
MINDY2	USP40	Q9NVE5	377
MINDY2	SLC13A5	Q86YT5	372
MINDY2	COMTD1	Q86VU5	367
MINDY2	CACFD1	Q9UGQ2	367
MINDY2	TSPYL5	Q86VY4	364
MINDY2	CEACAM18	A8MTB9	363
MINDY2	PHF21A	Q96BD5	358
MINDY2	MRFAP1L1	Q96HT8	355
MINDY2	GOLGA8K	D6RF30	355

IntAct

6 interactions, top by confidence:

A	B	Type	Score
KCNJ11	MINDY2	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CADPS	ACOT7	psi-mi:“MI:0914”(association)	0.350
MINDY2	SLC27A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): PTRH2 (Affinity Capture-MS), USP22 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), SLC27A2 (Affinity Capture-MS), CYP2J2 (Affinity Capture-MS), ARL13B (Affinity Capture-MS), XXYLT1 (Affinity Capture-MS), GNPAT (Affinity Capture-MS), NCR3LG1 (Affinity Capture-MS), GNA13 (Affinity Capture-MS), SCCPDH (Affinity Capture-MS), PPM1B (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), IKBIP (Affinity Capture-MS)

ESM2 similar proteins: A3KMI0, A3KQS4, A5PF44, A6QP16, A8E7C5, B1H2Q2, F4HZF0, O15226, O96838, P34550, Q09874, Q29FC1, Q2KI23, Q2KJ22, Q3SWY8, Q3T9Z9, Q3V0G7, Q4R4A2, Q5BJQ2, Q5R7G8, Q5U2S3, Q5VVW2, Q5XHY7, Q61502, Q6NZC7, Q6P158, Q6P5D3, Q6PDI6, Q6PGC1, Q75E61, Q76LS9, Q7M760, Q7TSI3, Q7XI08, Q7Z478, Q8C437, Q8GY87, Q8H106, Q8N5J2, Q8NBR6

Diamond homologs: A3KQS4, P53155, Q2KI23, Q2KJ22, Q5BJQ2, Q5R7G8, Q6PDI6, Q76LS9, Q8N5J2, Q8NBR6, Q08930, Q09874

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2345 predictions. Top by Δscore:

Variant	Effect	Δscore
15:58772233:A:T	donor_gain	1.0000
15:58787900:TTTCA:T	acceptor_loss	1.0000
15:58787901:TTCA:T	acceptor_loss	1.0000
15:58787902:TCAGG:T	acceptor_loss	1.0000
15:58787903:CAG:C	acceptor_loss	1.0000
15:58787904:A:AG	acceptor_gain	1.0000
15:58787904:A:C	acceptor_loss	1.0000
15:58787905:G:GA	acceptor_gain	1.0000
15:58787962:AGGTT:A	donor_loss	1.0000
15:58787964:G:GA	donor_loss	1.0000
15:58787964:G:GG	donor_gain	1.0000
15:58802308:TACA:T	acceptor_loss	1.0000
15:58802310:CA:C	acceptor_loss	1.0000
15:58802311:A:AG	acceptor_gain	1.0000
15:58802311:A:T	acceptor_loss	1.0000
15:58802311:AG:A	acceptor_gain	1.0000
15:58802312:G:GG	acceptor_gain	1.0000
15:58802312:GG:G	acceptor_gain	1.0000
15:58802312:GGA:G	acceptor_gain	1.0000
15:58802374:ACAGG:A	donor_loss	1.0000
15:58802375:CAGGT:C	donor_loss	1.0000
15:58802376:AGGT:A	donor_loss	1.0000
15:58802379:T:G	donor_loss	1.0000
15:58810222:A:AG	acceptor_gain	1.0000
15:58810223:T:G	acceptor_gain	1.0000
15:58810224:TTTCA:T	acceptor_loss	1.0000
15:58810225:TTCA:T	acceptor_loss	1.0000
15:58810226:TCAG:T	acceptor_loss	1.0000
15:58810227:CAG:C	acceptor_loss	1.0000
15:58810228:A:AC	acceptor_loss	1.0000

AlphaMissense

4071 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:58772122:T:G	Y243D	1.000
15:58772133:G:C	K246N	1.000
15:58772133:G:T	K246N	1.000
15:58772175:G:C	Q260H	1.000
15:58772175:G:T	Q260H	1.000
15:58772184:C:A	N263K	1.000
15:58772184:C:G	N263K	1.000
15:58772185:G:A	G264R	1.000
15:58772185:G:C	G264R	1.000
15:58772186:G:A	G264E	1.000
15:58772189:C:A	P265H	1.000
15:58772191:T:C	C266R	1.000
15:58772192:G:A	C266Y	1.000
15:58772193:C:G	C266W	1.000
15:58772195:C:A	P267H	1.000
15:58772204:C:A	A270D	1.000
15:58772214:T:A	N273K	1.000
15:58772214:T:G	N273K	1.000
15:58787949:T:C	L295P	1.000
15:58810264:T:C	L333P	1.000
15:58810272:G:C	G336R	1.000
15:58810272:G:T	G336C	1.000
15:58810273:G:A	G336D	1.000
15:58810276:T:C	L337P	1.000
15:58810282:T:A	V339E	1.000
15:58810286:T:A	N340K	1.000
15:58810286:T:G	N340K	1.000
15:58810293:T:C	F343L	1.000
15:58810294:T:C	F343S	1.000
15:58810295:C:A	F343L	1.000

dbSNP variants (sampled 300 via entrez): RS1000045122 (15:58794507 T>C), RS1000135771 (15:58825526 A>G), RS1000140295 (15:58817307 G>A), RS1000150256 (15:58849145 A>G), RS1000167084 (15:58825869 G>C,T), RS1000206956 (15:58789332 C>A,T), RS1000232770 (15:58784382 G>A,C), RS1000245087 (15:58799339 A>G), RS1000267179 (15:58784123 C>G,T), RS1000347283 (15:58859451 T>G), RS1000362316 (15:58819713 G>A), RS1000425900 (15:58813902 A>G), RS1000457031 (15:58814115 T>C,G), RS1000463864 (15:58851652 G>T), RS1000560634 (15:58846389 C>T)

Disease associations

OMIM: gene MIM:618408 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST012299_21	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	5.000000e-07
GCST012308_3	Schizophrenia	1.000000e-09
GCST012310_3	Schizophrenia x sex interaction	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
titanium dioxide	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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