MINDY3

Summary

MINDY3 (MINDY lysine 48 deubiquitinase 3, HGNC:23578) is a protein-coding gene on chromosome 10p13, encoding Ubiquitin carboxyl-terminal hydrolase MINDY-3 (Q9H8M7). Hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins.

The protein encoded by this gene contains a caspase-associated recruitment domain and may function in apoptosis. It has been identified as a tumor suppressor in lung and gastric cancers, and a polymorphism in the gene may be associated with gastric cancer risk. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 80013 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_024948

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23578
Approved symbol	MINDY3
Name	MINDY lysine 48 deubiquitinase 3
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13397, CARP, my042, DERP5
Ensembl gene	ENSG00000148481
Ensembl biotype	protein_coding
OMIM	611649
Entrez	80013

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000277632, ENST00000378036, ENST00000418767, ENST00000436829, ENST00000476912, ENST00000477891, ENST00000922923, ENST00000953409

RefSeq mRNA: 2 — MANE Select: NM_024948 NM_001318330, NM_024948

CCDS: CCDS7110

Canonical transcript exons

ENST00000277632 — 15 exons

Exon	Start	End
ENSE00001285483	15860206	15860507
ENSE00003459653	15837204	15837318
ENSE00003485661	15821656	15821726
ENSE00003527786	15833630	15833709
ENSE00003537348	15796100	15796172
ENSE00003548388	15786561	15786648
ENSE00003586148	15789247	15789319
ENSE00003600081	15782155	15782226
ENSE00003638576	15816835	15816915
ENSE00003639172	15834543	15834616
ENSE00003642118	15841426	15841599
ENSE00003667571	15847864	15847943
ENSE00003685315	15838228	15838279
ENSE00003688029	15843212	15843272
ENSE00003850119	15778174	15779141

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2193 / max 199.4382, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108446	21.2193	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	96.91	gold quality
calcaneal tendon	UBERON:0003701	94.58	gold quality
endocervix	UBERON:0000458	93.08	gold quality
pons	UBERON:0000988	92.90	gold quality
popliteal artery	UBERON:0002250	92.34	gold quality
tibial artery	UBERON:0007610	92.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.30	gold quality
rectum	UBERON:0001052	92.28	gold quality
artery	UBERON:0001637	92.14	gold quality
right coronary artery	UBERON:0001625	92.13	gold quality
right ovary	UBERON:0002118	92.04	gold quality
aorta	UBERON:0000947	92.01	gold quality
dorsal root ganglion	UBERON:0000044	91.97	gold quality
descending thoracic aorta	UBERON:0002345	91.94	gold quality
body of uterus	UBERON:0009853	91.94	gold quality
adrenal tissue	UBERON:0018303	91.92	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.88	gold quality
spinal cord	UBERON:0002240	91.85	gold quality
corpus callosum	UBERON:0002336	91.85	gold quality
ectocervix	UBERON:0012249	91.80	gold quality
left coronary artery	UBERON:0001626	91.74	gold quality
thoracic aorta	UBERON:0001515	91.65	gold quality
ascending aorta	UBERON:0001496	91.63	gold quality
secondary oocyte	CL:0000655	91.59	gold quality
left ovary	UBERON:0002119	91.52	gold quality
colonic epithelium	UBERON:0000397	91.47	gold quality
coronary artery	UBERON:0001621	91.23	gold quality
cerebellar vermis	UBERON:0004720	91.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.07	gold quality
skin of abdomen	UBERON:0001416	90.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting MINDY3, 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-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-548AJ-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 4)

• CARP is a novel caspase recruitment domain containing pro-apoptotic protein. (CARP, CARD containing Protein) (PMID:12054670)
• results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G(1)/S-regulatory proteins by interacting with JAB1 (PMID:21499297)
• CARP is a potential tumor suppressor of gastric carcinoma and the rs2297882 C>T phenotype of CARP may serve as a predictor of gastric carcinoma. (PMID:24870804)
• CircFAM188A Regulates Autophagy via miR-670-3p and ULK1 in Epithelial Ovarian Carcinoma. (PMID:39229655)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mindy3	ENSDARG00000028715
mus_musculus	Mindy3	ENSMUSG00000026767
rattus_norvegicus	Mindy3	ENSRNOG00000016955
drosophila_melanogaster	CG7332	FBGN0030973

Paralogs (2): MINDY4 (ENSG00000106125), MINDY4B (ENSG00000214237)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase MINDY-3 — Q9H8M7 (reviewed: Q9H8M7)

Alternative names: Dermal papilla-derived protein 5, Deubiquitinating enzyme MINDY-3, Protein CARP

All UniProt accessions (4): Q9H8M7, X6R9S5, X6RC30, X6RC97

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins.

Subunit / interactions. Interacts with COPS5.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed with high levels in heart, skeletal muscle, and kidney, and low levels in liver and brain. Also expressed in lung (at protein level).

Similarity. Belongs to the MINDY deubiquitinase family. FAM188 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H8M7-1	1	yes
Q9H8M7-2	2

RefSeq proteins (2): NP_001305259, NP_079224* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR025257	MINDY-3/4_CD	Domain
IPR039785	MINY3/4	Family

Pfam: PF13898

UniProt features (9 total): sequence conflict 4, active site 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8Q06	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8M7-F1	88.52	0.75

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 (2): 51 (nucleophile); 287 (proton acceptor)

Post-translational modifications (1): 125

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): GTTAAAG_MIR302B, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, ATGTTAA_MIR302C, chr10p13, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_K48_LINKED_DEUBIQUITINATION, GOCC_NUCLEAR_ENVELOPE, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_PROTEOLYSIS, GOCC_NUCLEAR_MEMBRANE, SCGGAAGY_ELK1_02

GO Biological Process (3): proteolysis (GO:0006508), apoptotic process (GO:0006915), protein K48-linked deubiquitination (GO:0071108)

GO Molecular Function (6): cysteine-type deubiquitinase activity (GO:0004843), K48-linked deubiquitinase activity (GO:1990380), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleoplasm (GO:0005654), nuclear membrane (GO:0031965), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deubiquitinase activity	2
protein metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
protein deubiquitination	1
cysteine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1
nucleus	1
nuclear envelope	1
organelle membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

595 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MINDY3	TMEM45A	Q9NWC5	868
MINDY3	CARD6	Q9BX69	805
MINDY3	GHITM	Q9H3K2	800
MINDY3	TMEM9	Q9P0T7	775
MINDY3	COPS7A	Q9UBW8	771
MINDY3	CRADD	P78560	727
MINDY3	CASP1	P29466	713
MINDY3	CARD8	Q9Y2G2	713
MINDY3	NLRP1	Q9C000	665
MINDY3	APAF1	O14727	652
MINDY3	URGCP	Q8TCY9	637
MINDY3	BCL10	O95999	632
MINDY3	NOD1	Q9Y239	605
MINDY3	RIPK2	O43353	591
MINDY3	RIPK1	Q13546	555
MINDY3	RIGI	O95786	555

IntAct

49 interactions, top by confidence:

A	B	Type	Score
RAD23A	MINDY3	psi-mi:“MI:0915”(physical association)	0.780
TRIM49	CKS1B	psi-mi:“MI:0914”(association)	0.740
TRIM49	MINDY3	psi-mi:“MI:0915”(physical association)	0.740
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
SDCBP	MINDY3	psi-mi:“MI:0915”(physical association)	0.560
TRIM49C	MINDY3	psi-mi:“MI:0915”(physical association)	0.560
DAZAP2	MINDY3	psi-mi:“MI:0915”(physical association)	0.560
COPS5	MINDY3	psi-mi:“MI:0915”(physical association)	0.540
MINDY3	COPS5	psi-mi:“MI:0403”(colocalization)	0.540
DOK2	NCK2	psi-mi:“MI:0914”(association)	0.530
MOS	CLUH	psi-mi:“MI:0914”(association)	0.530
MINDY3	UBB	psi-mi:“MI:0914”(association)	0.530
KIF9	MINDY3	psi-mi:“MI:0915”(physical association)	0.400
ORF69	PEPD	psi-mi:“MI:0914”(association)	0.350
TRAF2	UMAD1	psi-mi:“MI:0914”(association)	0.350
RBCK1	UMAD1	psi-mi:“MI:0914”(association)	0.350
TRADD	HNRNPCL2	psi-mi:“MI:0914”(association)	0.350
TRAF2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
CD19	POLR2M	psi-mi:“MI:0914”(association)	0.350
RFX3	IGSF8	psi-mi:“MI:0914”(association)	0.350

BioGRID (80): FAM188A (Two-hybrid), FAM188A (Biochemical Activity), UBB (Affinity Capture-MS), RNF25 (Affinity Capture-MS), LIN7A (Affinity Capture-MS), MPP6 (Affinity Capture-MS), MCM3 (Affinity Capture-MS), MCM5 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), KIFC1 (Affinity Capture-MS), ZNF644 (Affinity Capture-MS), RPUSD3 (Affinity Capture-MS), LANCL2 (Affinity Capture-MS), HNRNPLL (Affinity Capture-MS), CSK (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2QC33, A0FKG7, A6H7H7, F1N9S8, O95453, P0C0T1, P42694, P50747, P69341, Q0IIH8, Q0VGM9, Q13572, Q28559, Q4R528, Q5BJZ6, Q5F480, Q5R699, Q5RC51, Q5ZIA0, Q5ZIW7, Q640G7, Q6DDJ3, Q6DFV5, Q6DG88, Q6DJB3, Q6GR37, Q6NYU2, Q6PZ02, Q6PZ03, Q6PZ05, Q7T0P6, Q80UY1, Q80YV4, Q811C2, Q8BGE6, Q8BYN3, Q8C9S8, Q8N4J0, Q8VDG3, Q8WYN0

Diamond homologs: A0AUR5, D2DGW3, Q0IIH8, Q4R528, Q6NX27, Q9CV28, Q9H8M7, Q9VWN5, P47948, P47949, Q0VA42, Q1A7B1, A1A4L4, A8MYZ0, Q3UQI9, Q4G0A6, Q5RF72

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	MINDY3	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2853 predictions. Top by Δscore:

Variant	Effect	Δscore
10:15786649:C:CC	acceptor_gain	1.0000
10:15789232:T:TA	donor_gain	1.0000
10:15789241:G:C	donor_gain	1.0000
10:15789245:A:AC	donor_gain	1.0000
10:15789246:C:CC	donor_gain	1.0000
10:15789246:CT:C	donor_gain	1.0000
10:15789246:CTA:C	donor_gain	1.0000
10:15789246:CTATT:C	donor_gain	1.0000
10:15796094:TTTTA:T	donor_loss	1.0000
10:15796095:TTTA:T	donor_loss	1.0000
10:15796096:TTA:T	donor_loss	1.0000
10:15796097:TA:T	donor_loss	1.0000
10:15796099:CCTT:C	donor_gain	1.0000
10:15796168:ATATC:A	acceptor_gain	1.0000
10:15796169:TATC:T	acceptor_gain	1.0000
10:15796170:ATC:A	acceptor_gain	1.0000
10:15796171:TC:T	acceptor_gain	1.0000
10:15796172:CC:C	acceptor_gain	1.0000
10:15796173:C:CC	acceptor_gain	1.0000
10:15796173:CTG:C	acceptor_loss	1.0000
10:15833710:C:CC	acceptor_gain	1.0000
10:15834538:ATTAC:A	donor_loss	1.0000
10:15834539:TTA:T	donor_loss	1.0000
10:15834540:TACCT:T	donor_loss	1.0000
10:15834545:G:A	donor_gain	1.0000
10:15834613:TGCC:T	acceptor_gain	1.0000
10:15834614:GCC:G	acceptor_gain	1.0000
10:15834615:CC:C	acceptor_gain	1.0000
10:15834615:CCC:C	acceptor_gain	1.0000
10:15834616:CC:C	acceptor_gain	1.0000

AlphaMissense

2904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:15782183:C:T	G387E	1.000
10:15782185:A:C	N386K	1.000
10:15782185:A:T	N386K	1.000
10:15789309:G:C	F322L	1.000
10:15789309:G:T	F322L	1.000
10:15789311:A:G	F322L	1.000
10:15796120:A:G	F312S	1.000
10:15816851:G:A	T289I	1.000
10:15816856:G:C	H287Q	1.000
10:15816856:G:T	H287Q	1.000
10:15816858:G:C	H287D	1.000
10:15816879:A:G	W280R	1.000
10:15816879:A:T	W280R	1.000
10:15821693:C:T	G255E	1.000
10:15833692:A:G	L223P	1.000
10:15834552:C:T	G214E	1.000
10:15860213:C:A	W29C	1.000
10:15860213:C:G	W29C	1.000
10:15860215:A:G	W29R	1.000
10:15860215:A:T	W29R	1.000
10:15779024:A:G	W436R	0.999
10:15779024:A:T	W436R	0.999
10:15779045:A:G	W429R	0.999
10:15779045:A:T	W429R	0.999
10:15779056:A:G	L425P	0.999
10:15779058:A:C	C424W	0.999
10:15779126:C:A	G402W	0.999
10:15779126:C:G	G402R	0.999
10:15779126:C:T	G402R	0.999
10:15782184:C:G	G387R	0.999

dbSNP variants (sampled 300 via entrez): RS1000053351 (10:15854736 T>C), RS1000084003 (10:15855006 A>C,T), RS1000117553 (10:15806069 T>C), RS1000160339 (10:15847304 G>A), RS1000187660 (10:15809758 CAT>C), RS1000248783 (10:15815837 G>A), RS1000262898 (10:15794876 A>G), RS1000310198 (10:15851848 T>C), RS1000336866 (10:15827411 T>C), RS1000363690 (10:15788279 A>C), RS1000443298 (10:15847534 T>TG), RS1000446501 (10:15817039 G>A,C,T), RS1000479790 (10:15788611 A>G), RS1000529076 (10:15833067 T>C), RS1000594738 (10:15852955 A>C,T)

Disease associations

OMIM: gene MIM:611649 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002450_7	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	8.000000e-06
GCST002826_14	Urate levels (BMI interaction)	3.000000e-06
GCST002875_15	Diisocyanate-induced asthma	1.000000e-06
GCST008151_4	Waist circumference	5.000000e-06
GCST008160_49	Waist circumference	5.000000e-06
GCST008398_12	Glycated hemoglobin levels	3.000000e-07
GCST90002396_478	Mean reticulocyte volume	2.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0006995	response to diisocyanate
EFO:0004541	HbA1c measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	3
Aflatoxin B1	decreases methylation, increases methylation	3
Cyclosporine	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Troglitazone	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	affects methylation	1
Methyl Methanesulfonate	increases expression	1
Testosterone	decreases expression	1

Clinical trials (associated diseases)

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