MINDY4

Summary

MINDY4 (MINDY lysine 48 deubiquitinase 4, HGNC:21916) is a protein-coding gene on chromosome 7p14.3, encoding Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (Q4G0A6). Probable hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins.

Predicted to enable K48-linked deubiquitinase activity. Predicted to be involved in protein K48-linked deubiquitination and proteolysis.

Source: NCBI Gene 84182 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_032222

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21916
Approved symbol	MINDY4
Name	MINDY lysine 48 deubiquitinase 4
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22374
Ensembl gene	ENSG00000106125
Ensembl biotype	protein_coding
OMIM	621315
Entrez	84182

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000265299, ENST00000409881, ENST00000494187, ENST00000852494, ENST00000852495

RefSeq mRNA: 1 — MANE Select: NM_032222 NM_032222

CCDS: CCDS43565

Canonical transcript exons

ENST00000265299 — 18 exons

Exon	Start	End
ENSE00001908624	30891957	30892387
ENSE00002203309	30771417	30771556
ENSE00003463334	30778432	30778551
ENSE00003468210	30850454	30850555
ENSE00003477977	30882921	30882993
ENSE00003480103	30872243	30872306
ENSE00003482798	30828679	30828737
ENSE00003485548	30859257	30859324
ENSE00003491284	30852216	30852279
ENSE00003492943	30882181	30882361
ENSE00003513855	30840760	30840848
ENSE00003520293	30785749	30785992
ENSE00003598723	30853394	30853459
ENSE00003611129	30791165	30791574
ENSE00003622993	30839200	30839316
ENSE00003645812	30781977	30782212
ENSE00003652576	30836658	30836764
ENSE00003663486	30875495	30875656

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 88.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3699 / max 108.5483, expressed in 1635 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78005	9.7667	1623
78006	0.3582	189
78007	0.2449	109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.94	gold quality
right coronary artery	UBERON:0001625	83.77	gold quality
fallopian tube	UBERON:0003889	82.59	gold quality
right ovary	UBERON:0002118	81.84	gold quality
left coronary artery	UBERON:0001626	81.66	gold quality
left ovary	UBERON:0002119	81.06	gold quality
right lung	UBERON:0002167	80.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.58	gold quality
upper lobe of left lung	UBERON:0008952	80.56	gold quality
ovary	UBERON:0000992	80.53	gold quality
lower esophagus	UBERON:0013473	80.52	gold quality
ascending aorta	UBERON:0001496	80.35	gold quality
thoracic aorta	UBERON:0001515	80.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.08	gold quality
popliteal artery	UBERON:0002250	79.79	gold quality
tibial artery	UBERON:0007610	79.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.52	gold quality
left uterine tube	UBERON:0001303	79.46	gold quality
lung	UBERON:0002048	79.19	gold quality
right testis	UBERON:0004534	78.67	gold quality
testis	UBERON:0000473	78.50	gold quality
right lobe of thyroid gland	UBERON:0001119	78.42	gold quality
left lobe of thyroid gland	UBERON:0001120	77.95	gold quality
thyroid gland	UBERON:0002046	77.95	gold quality
left testis	UBERON:0004533	77.65	gold quality
ventricular zone	UBERON:0003053	77.51	gold quality
descending thoracic aorta	UBERON:0002345	77.36	gold quality
smooth muscle tissue	UBERON:0001135	77.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting MINDY4, 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-4533	100.00	69.48	2758
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-6858-3P	96.37	64.41	771
HSA-MIR-3170	95.84	64.32	721
HSA-MIR-598-5P	92.45	70.36	75

Literature-anchored findings (GeneRIF, showing 1)

• FAM188B is a putative oncogene that functions via interaction with USP7. (PMID:29795372)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mindy4	ENSDARG00000077696
mus_musculus	Mindy4	ENSMUSG00000038022
rattus_norvegicus	Mindy4	ENSRNOG00000011530
drosophila_melanogaster	CG14142	FBGN0036143

Paralogs (2): MINDY3 (ENSG00000148481), MINDY4B (ENSG00000214237)

Protein

Protein identifiers

Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 — Q4G0A6 (reviewed: Q4G0A6)

Alternative names: Probable deubiquitinating enzyme MINDY-4

All UniProt accessions (1): Q4G0A6

UniProt curated annotations — full annotation on UniProt →

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

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

RefSeq proteins (1): NP_115598* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025257	MINDY-3/4_CD	Domain
IPR039785	MINY3/4	Family
IPR059022	MINDY4_N	Domain

Pfam: PF13898, PF26038

UniProt features (23 total): sequence variant 7, sequence conflict 4, compositionally biased region 4, modified residue 3, region of interest 2, active site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0A6-F1	68.40	0.46

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): 456 (nucleophile); 677 (proton acceptor)

Post-translational modifications (3): 223, 289, 219

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, CAGCAGG_MIR370, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, CCTGTGA_MIR513, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_K48_LINKED_DEUBIQUITINATION, CERVERA_SDHB_TARGETS_1_UP, AACTGGA_MIR145, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, P53_02, GOMF_UBIQUITIN_LIKE_PROTEIN_PEPTIDASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, LEE_BMP2_TARGETS_UP

GO Biological Process (2): proteolysis (GO:0006508), protein K48-linked deubiquitination (GO:0071108)

GO Molecular Function (5): cysteine-type deubiquitinase activity (GO:0004843), K48-linked deubiquitinase activity (GO:1990380), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deubiquitinase activity	2
protein metabolic process	1
protein deubiquitination	1
cysteine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MINDY4	MINDY1	Q8N5J2	649
MINDY4	INMT	O95050	577
MINDY4	MINDY2	Q8NBR6	545
MINDY4	USP22	Q9UPT9	458
MINDY4	FAM228B	P0C875	455
MINDY4	KCTD18	Q6PI47	455
MINDY4	C2orf74	A8MZ97	447
MINDY4	DGKH	Q86XP1	434
MINDY4	TSPYL5	Q86VY4	433
MINDY4	SIRPD	Q9H106	419
MINDY4	SANBR	Q6NSI8	418
MINDY4	OR10H3	O60404	404
MINDY4	RGS14	O43566	397
MINDY4	C2CD2	Q9Y426	388
MINDY4	CIMIP6	Q8N5S3	379

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MINDY4	TRIM56	psi-mi:“MI:0915”(physical association)	0.000
MINDY4	AGMAT	psi-mi:“MI:0915”(physical association)	0.000
MINDY4	NFKBIL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (78): AGMAT (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), FAM188B (Reconstituted Complex), RAD50 (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), SF3B4 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), PRPF8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), DSP (Affinity Capture-MS), EEF1G (Affinity Capture-MS), SF3B1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM13, A1A4L4, A2RRS8, B0DOB4, D4A039, O00750, O70167, O70173, Q08EC4, Q1LXR6, Q3ULW6, Q3UQI9, Q3V0L5, Q3ZAV8, Q4AC94, Q4G0A6, Q52KB6, Q5DTU0, Q5F479, Q5JV73, Q5SUS0, Q5T0N1, Q5XIR4, Q5XIZ9, Q6IFT4, Q6IRN0, Q6IRU7, Q6P1H6, Q6P4K6, Q6PF55, Q6REY9, Q6ZPF3, Q7TP65, Q7Z2Z1, Q80TQ5, Q80VH0, Q8C008, Q8IWE5, Q8N4X5, Q8N5R6

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

4492 predictions. Top by Δscore:

Variant	Effect	Δscore
7:30771538:G:GT	donor_gain	1.0000
7:30771552:GAAAG:G	donor_gain	1.0000
7:30771553:AAAGG:A	donor_loss	1.0000
7:30771557:G:GA	donor_loss	1.0000
7:30771558:T:A	donor_loss	1.0000
7:30771585:G:GT	donor_gain	1.0000
7:30781969:AAT:A	acceptor_gain	1.0000
7:30781971:T:TA	acceptor_gain	1.0000
7:30781973:ATAG:A	acceptor_loss	1.0000
7:30781975:A:AG	acceptor_gain	1.0000
7:30781975:AGGC:A	acceptor_loss	1.0000
7:30781976:G:GG	acceptor_gain	1.0000
7:30781976:G:T	acceptor_loss	1.0000
7:30836656:A:AG	acceptor_gain	1.0000
7:30836656:AGAG:A	acceptor_gain	1.0000
7:30836657:G:GA	acceptor_gain	1.0000
7:30836657:GA:G	acceptor_gain	1.0000
7:30836657:GAGG:G	acceptor_gain	1.0000
7:30836761:AAAGG:A	donor_loss	1.0000
7:30836763:AGGTA:A	donor_loss	1.0000
7:30836765:GT:G	donor_loss	1.0000
7:30836766:T:G	donor_loss	1.0000
7:30840849:G:GG	donor_gain	1.0000
7:30850551:GCACT:G	donor_gain	1.0000
7:30850556:G:GG	donor_gain	1.0000
7:30852280:G:GG	donor_gain	1.0000
7:30875613:A:AG	donor_gain	1.0000
7:30771515:G:GT	donor_gain	0.9900
7:30771534:TCAGG:T	donor_gain	0.9900
7:30778548:CAAGG:C	donor_loss	0.9900

AlphaMissense

4955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:30839251:T:A	W431R	0.999
7:30839251:T:C	W431R	0.999
7:30875508:T:C	L608P	0.997
7:30882217:T:A	W670R	0.997
7:30882217:T:C	W670R	0.997
7:30891958:T:A	W743R	0.997
7:30891958:T:C	W743R	0.997
7:30891979:T:A	W750R	0.997
7:30891979:T:C	W750R	0.997
7:30882244:A:C	S679R	0.996
7:30882246:C:A	S679R	0.996
7:30882246:C:G	S679R	0.996
7:30882353:T:C	L715P	0.996
7:30882982:C:G	C738W	0.995
7:30839253:G:C	W431C	0.994
7:30839253:G:T	W431C	0.994
7:30875619:G:A	G645D	0.994
7:30882238:C:G	H677D	0.994
7:30882984:T:A	I739N	0.994
7:30840788:T:A	V462D	0.993
7:30872300:T:G	C601W	0.993
7:30875625:T:C	L647S	0.993
7:30882224:T:A	V672D	0.993
7:30891960:G:C	W743C	0.993
7:30891960:G:T	W743C	0.993
7:30891981:G:C	W750C	0.993
7:30891981:G:T	W750C	0.993
7:30771542:T:C	F17L	0.992
7:30771544:C:A	F17L	0.992
7:30771544:C:G	F17L	0.992

dbSNP variants (sampled 300 via entrez): RS1000036169 (7:30840470 A>G), RS1000075121 (7:30826106 A>G), RS1000108453 (7:30847607 A>G), RS1000113570 (7:30884144 G>A), RS1000133574 (7:30776941 G>C), RS1000136353 (7:30839909 G>C,T), RS1000142277 (7:30831836 A>G), RS1000165821 (7:30854904 G>A), RS1000167747 (7:30802030 T>C), RS1000186195 (7:30868735 T>G), RS1000218892 (7:30792299 C>A,T), RS1000230814 (7:30817590 G>C), RS1000237634 (7:30823606 A>G), RS1000322722 (7:30795510 G>A), RS1000333595 (7:30834757 A>G)

Disease associations

OMIM: gene MIM:621315 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001432_2	Nephrolithiasis	2.000000e-14
GCST004691_13	Huntington’s disease progression	5.000000e-06
GCST005175_53	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	8.000000e-06
GCST007267_80	Systolic blood pressure	4.000000e-10
GCST007833_8	Urolithiasis	5.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0004723	coronary artery calcification
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Cytarabine	decreases expression	1
Methapyrilene	increases methylation	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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