OTULINL

Summary

OTULINL (OTU deubiquitinase with linear linkage specificity like, HGNC:25629) is a protein-coding gene on chromosome 5p15.2, encoding Inactive ubiquitin thioesterase OTULINL (Q9NUU6). Lacks deubiquitinase activity.

Located in cytoplasmic side of endoplasmic reticulum membrane and nuclear envelope.

Source: NCBI Gene 54491 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_019018

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25629
Approved symbol	OTULINL
Name	OTU deubiquitinase with linear linkage specificity like
Location	5p15.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11127, NET20
Ensembl gene	ENSG00000145569
Ensembl biotype	protein_coding
Entrez	54491

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000274217, ENST00000506258, ENST00000513825, ENST00000853045, ENST00000955066, ENST00000955068, ENST00000955069

RefSeq mRNA: 1 — MANE Select: NM_019018 NM_019018

CCDS: CCDS3884

Canonical transcript exons

ENST00000274217 — 8 exons

Exon	Start	End
ENSE00000971039	14607330	14607458
ENSE00001123252	14608748	14609017
ENSE00001123267	14601351	14601442
ENSE00001262918	14581792	14581958
ENSE00001310885	14610141	14616180
ENSE00003460819	14601213	14601244
ENSE00003604513	14600965	14601124
ENSE00003671675	14602183	14602332

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 92.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4189 / max 291.8326, expressed in 1019 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55821	9.0718	1012
55820	0.3471	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	92.35	gold quality
mononuclear cell	CL:0000842	91.96	gold quality
leukocyte	CL:0000738	91.61	gold quality
buccal mucosa cell	CL:0002336	91.53	gold quality
islet of Langerhans	UBERON:0000006	88.65	gold quality
palpebral conjunctiva	UBERON:0001812	87.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.93	gold quality
secondary oocyte	CL:0000655	86.65	gold quality
right lung	UBERON:0002167	85.93	gold quality
stromal cell of endometrium	CL:0002255	85.81	gold quality
rectum	UBERON:0001052	85.50	gold quality
colonic mucosa	UBERON:0000317	85.33	gold quality
lower lobe of lung	UBERON:0008949	85.10	gold quality
decidua	UBERON:0002450	85.06	gold quality
bone marrow	UBERON:0002371	84.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.32	gold quality
upper lobe of lung	UBERON:0008948	83.43	gold quality
upper lobe of left lung	UBERON:0008952	83.41	gold quality
granulocyte	CL:0000094	82.97	gold quality
eye	UBERON:0000970	81.82	gold quality
mucosa of transverse colon	UBERON:0004991	81.49	gold quality
colonic epithelium	UBERON:0000397	81.43	gold quality
bone marrow cell	CL:0002092	81.40	gold quality
oocyte	CL:0000023	81.35	gold quality
blood	UBERON:0000178	80.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.30	gold quality
vermiform appendix	UBERON:0001154	79.31	gold quality
lung	UBERON:0002048	79.06	gold quality
tendon of biceps brachii	UBERON:0008188	78.75	silver quality
pancreas	UBERON:0001264	78.31	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	20.97
E-MTAB-5061	yes	18.62
E-CURD-112	yes	13.19
E-CURD-114	yes	11.82
E-GEOD-81547	yes	11.02
E-GEOD-83139	yes	8.02
E-ANND-3	yes	7.83
E-GEOD-99795	no	228.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

244 targeting OTULINL, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
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-7110-3P	100.00	73.18	2486
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 2)

• The crystal structure of FAM105A/OTULINL indicated that the OTU domain possesses structural deficiencies in both active site and substrate-binding infrastructure predicted to impair normal deubiquitinase (DUB) function. (PMID:31056421)
• Disrupting of family with sequence similarity 105, member A (Fam105a) deteriorates pancreatic beta-cell physiology and insulin secretion in INS-1 cells. (PMID:37311518)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Otulinl	ENSMUSG00000056069
rattus_norvegicus	Otulinl	ENSRNOG00000012109

Paralogs (1): OTULIN (ENSG00000154124)

Protein

Protein identifiers

Inactive ubiquitin thioesterase OTULINL — Q9NUU6 (reviewed: Q9NUU6)

All UniProt accessions (1): Q9NUU6

UniProt curated annotations — full annotation on UniProt →

Function. Lacks deubiquitinase activity.

Subunit / interactions. Does not bind ubiquitin or ubiquitin-like proteins.

Subcellular location. Cytoplasm. Endoplasmic reticulum membrane. Nucleus envelope.

Domain organisation. The N-terminal region that precedes the OTU domain mediates interaction with cellular membranes.

Similarity. Belongs to the peptidase C65 family. Otulin subfamily.

RefSeq proteins (1): NP_061891* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023235	FAM105	Family
IPR023236	OTULINL	Family

Pfam: PF16218

UniProt features (34 total): helix 19, strand 5, mutagenesis site 3, region of interest 2, chain 1, domain 1, turn 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6DRM	X-RAY DIFFRACTION	2.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUU6-F1	89.22	0.76

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 (3):

Position	Phenotype
2–83	loss of membrane binding.
139	fails to confer catalytic activity; when associated with n-352.
352	fails to confer catalytic activity; when associated with c-139.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 273 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, PEREZ_TP63_TARGETS, GOZGIT_ESR1_TARGETS_DN, MODULE_493, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GNF2_MCL1, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, CORRE_MULTIPLE_MYELOMA_UP, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, LYF1_01, SANSOM_APC_TARGETS_DN, PEREZ_TP53_AND_TP63_TARGETS, FOXJ2_02, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (0):

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

GO Cellular Component (7): nuclear envelope (GO:0005635), cytoplasm (GO:0005737), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
binding	1
nucleus	1
organelle envelope	1
intracellular anatomical structure	1
endoplasmic reticulum membrane	1
cytoplasmic side of membrane	1
cytoplasm	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OTULINL	TMEM63C	Q9P1W3	521
OTULINL	OTUD6A	Q7L8S5	495
OTULINL	OTUD4	Q01804	494
OTULINL	OTUD5	Q96G74	477
OTULINL	OTUD3	Q5T2D3	469
OTULINL	OTUD6B	Q8N6M0	461
OTULINL	CEP15	Q9HBI5	460
OTULINL	OTUD7A	Q8TE49	456
OTULINL	ZRANB1	Q9UGI0	447
OTULINL	OTUD1	Q5VV17	443
OTULINL	OTUB2	Q96DC9	435
OTULINL	ALG13	Q9NP73	430
OTULINL	TTC1	Q99614	419
OTULINL	FKBP5	Q13451	413
OTULINL	OTUD7B	Q6GQQ9	392

IntAct

52 interactions, top by confidence:

A	B	Type	Score
OTULINL	TMX2	psi-mi:“MI:0915”(physical association)	0.560
HSD17B11	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
RETREG3	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
AQP6	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
GOLT1A	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
KLF11	OTULINL	psi-mi:“MI:0915”(physical association)	0.560
OTULINL	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF17	TSPAN6	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ACKR3	PDE2A	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
FPR1	NBAS	psi-mi:“MI:0914”(association)	0.350
SCN3B	NBAS	psi-mi:“MI:0914”(association)	0.350
MFSD6	EIF3CL	psi-mi:“MI:0914”(association)	0.350
SLC19A3	SNAP23	psi-mi:“MI:0914”(association)	0.350
SLC39A10	CASK	psi-mi:“MI:0914”(association)	0.350
SLC39A8	CEBPZOS	psi-mi:“MI:0914”(association)	0.350

BioGRID (421): FAM105A (Affinity Capture-MS), FAM105A (Affinity Capture-RNA), FAM105A (Affinity Capture-MS), FAM105A (Affinity Capture-Western), MARCH1 (Proximity Label-MS), MARCH2 (Proximity Label-MS), TEX264 (Proximity Label-MS), ATP6AP2 (Proximity Label-MS), ESYT1 (Proximity Label-MS), NUP155 (Proximity Label-MS), SEC63 (Proximity Label-MS), TOR1AIP1 (Proximity Label-MS), RTN1 (Proximity Label-MS), RABL3 (Proximity Label-MS), SLC33A1 (Proximity Label-MS)

ESM2 similar proteins: A0AUR5, A1A4L4, A1L3F5, A4IIA7, A8MYZ0, D4ACE5, F1MDL2, F6U5F9, H2LP95, O15259, P79457, Q059U7, Q0IIH8, Q149N8, Q29RL0, Q2I0E5, Q2QKL5, Q2TE74, Q3B7D8, Q3B7T1, Q3TTL0, Q3UD82, Q3UQI9, Q4G0A6, Q4R4D7, Q4R796, Q502W6, Q5JPI3, Q5R9R1, Q5RF72, Q66H33, Q66J91, Q6GQV7, Q6NX27, Q6NXY1, Q6RI63, Q811C2, Q8C0W1, Q8CDG3, Q8CF97

Diamond homologs: Q3B7D8, Q3TVP5, Q3UCV8, Q96BN8, Q9NUU6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1313 predictions. Top by Δscore:

Variant	Effect	Δscore
5:14581955:GCAG:G	donor_gain	1.0000
5:14581959:G:GG	donor_gain	1.0000
5:14581960:T:A	donor_loss	1.0000
5:14600951:T:A	acceptor_gain	1.0000
5:14600954:A:AG	acceptor_gain	1.0000
5:14600955:A:G	acceptor_gain	1.0000
5:14600960:CATA:C	acceptor_loss	1.0000
5:14600961:ATAG:A	acceptor_gain	1.0000
5:14600962:T:G	acceptor_gain	1.0000
5:14600963:A:G	acceptor_loss	1.0000
5:14600963:AG:A	acceptor_gain	1.0000
5:14600964:GG:G	acceptor_gain	1.0000
5:14600964:GGA:G	acceptor_gain	1.0000
5:14600964:GGAA:G	acceptor_gain	1.0000
5:14601122:ATG:A	donor_gain	1.0000
5:14601123:TGG:T	donor_loss	1.0000
5:14601125:G:GG	donor_gain	1.0000
5:14601126:T:A	donor_loss	1.0000
5:14601245:G:GG	donor_gain	1.0000
5:14601439:G:GT	donor_gain	1.0000
5:14601440:A:T	donor_gain	1.0000
5:14602178:ATTAG:A	acceptor_gain	1.0000
5:14602328:TTAAG:T	donor_loss	1.0000
5:14602329:TAAG:T	donor_loss	1.0000
5:14602330:AAGG:A	donor_loss	1.0000
5:14602333:G:C	donor_loss	1.0000
5:14602334:T:A	donor_loss	1.0000
5:14607327:A:AG	acceptor_gain	1.0000
5:14607328:A:G	acceptor_gain	1.0000
5:14607456:CAGGT:C	donor_loss	1.0000

AlphaMissense

2350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:14607366:T:A	W179R	0.997
5:14607366:T:C	W179R	0.997
5:14608748:T:A	W210R	0.993
5:14608748:T:C	W210R	0.993
5:14607378:T:G	Y183D	0.992
5:14608863:T:C	L248P	0.991
5:14607368:G:C	W179C	0.989
5:14607368:G:T	W179C	0.989
5:14607427:T:C	L199P	0.989
5:14608854:T:C	F245S	0.989
5:14608844:G:C	A242P	0.988
5:14608852:G:C	K244N	0.988
5:14608852:G:T	K244N	0.988
5:14607430:G:C	R200P	0.986
5:14607343:T:C	L171P	0.985
5:14607384:T:C	F185L	0.985
5:14607386:T:A	F185L	0.985
5:14607386:T:G	F185L	0.985
5:14602259:G:C	R142T	0.982
5:14602260:A:C	R142S	0.981
5:14602260:A:T	R142S	0.981
5:14607379:A:C	Y183S	0.981
5:14607334:C:G	P168R	0.980
5:14602226:G:C	R131P	0.978
5:14607334:C:A	P168H	0.978
5:14607370:T:G	I180S	0.978
5:14607448:T:C	L206S	0.978
5:14608850:A:G	K244E	0.978
5:14602259:G:T	R142I	0.977
5:14607370:T:A	I180N	0.976

dbSNP variants (sampled 300 via entrez): RS1000134634 (5:14580166 A>G), RS1000267043 (5:14592900 G>A), RS1000298671 (5:14585046 C>G,T), RS1000373875 (5:14598157 G>A,T), RS1000501393 (5:14600589 G>C), RS1000710443 (5:14589490 G>C,T), RS1000770546 (5:14606402 C>T), RS1000903476 (5:14582586 G>C), RS1000988524 (5:14594517 G>T), RS1001036710 (5:14583725 C>G), RS1001071061 (5:14608126 G>A), RS1001109354 (5:14596959 T>C), RS1001132472 (5:14605369 T>C), RS1001225942 (5:14605604 C>T), RS1001228638 (5:14600305 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST005038_41	Allergic disease (asthma, hay fever or eczema)	1.000000e-12
GCST005990_49	Non-albumin protein levels	2.000000e-08
GCST007797_40	Asthma onset (childhood vs adult)	6.000000e-06
GCST007798_68	Asthma	9.000000e-13
GCST007800_35	Asthma (childhood onset)	1.000000e-23
GCST007941_38	Medication use (adrenergics, inhalants)	1.000000e-10
GCST007995_21	Asthma (childhood onset)	9.000000e-16
GCST008916_104	Asthma	4.000000e-12
GCST009720_100	Asthma	8.000000e-13
GCST009798_56	Asthma	5.000000e-13
GCST010042_132	Asthma	3.000000e-17
GCST010043_124	Asthma	2.000000e-15
GCST90002381_215	Eosinophil count	1.000000e-10
GCST90014325_19	Asthma	3.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0009941	Inhalant adrenergic use measurement
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Progesterone	affects cotreatment, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	increases expression	2
Cisplatin	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression	2
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	increases expression	1
diallyl trisulfide	decreases expression	1
pentanal	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
licochalcone B	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	decreases expression, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Hydrogen Peroxide	affects expression	1
Niclosamide	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	decreases expression	1

Clinical trials (associated diseases)

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