TINAG

Summary

TINAG (tubulointerstitial nephritis antigen, HGNC:14599) is a protein-coding gene on chromosome 6p12.1, encoding Tubulointerstitial nephritis antigen (Q9UJW2). Mediates adhesion of proximal tubule epithelial cells via integrins alpha3-beta1 and alphaV-beta3.

This gene encodes a glycoprotein that is restricted within the kidney to the basement membranes underlying the epithelium of Bowman’s capsule and proximal and distal tubules. Autoantibodies against this protein are found in sera of patients with tubulointerstital nephritis, membranous nephropathy and anti-glomerular basement membrane nephritis. Ontogeny studies suggest that the expression of this antigen is developmentally regulated in a precise spatial and temporal pattern throughout nephrogenesis.

Source: NCBI Gene 27283 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_014464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14599
Approved symbol	TINAG
Name	tubulointerstitial nephritis antigen
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137251
Ensembl biotype	protein_coding
OMIM	606749
Entrez	27283

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000259782, ENST00000370864, ENST00000370869, ENST00000486436

RefSeq mRNA: 1 — MANE Select: NM_014464 NM_014464

CCDS: CCDS4955

Canonical transcript exons

ENST00000259782 — 11 exons

Exon	Start	End
ENSE00000929875	54351352	54351397
ENSE00001135267	54347367	54347517
ENSE00001135276	54343226	54343349
ENSE00001135311	54380526	54380571
ENSE00001135319	54354513	54354636
ENSE00001385797	54389791	54390142
ENSE00001939598	54308441	54308905
ENSE00003523720	54320579	54320642
ENSE00003569377	54326802	54326916
ENSE00003606961	54321297	54321386
ENSE00003688363	54349716	54349896

Expression profiles

Bgee: expression breadth broad, 76 present calls, max score 96.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2823 / max 76.9980, expressed in 50 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68299	0.2304	45
68298	0.0212	9
68297	0.0182	10
68296	0.0125	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	96.75	gold quality
ileal mucosa	UBERON:0000331	94.96	gold quality
adult mammalian kidney	UBERON:0000082	90.68	gold quality
rectum	UBERON:0001052	87.33	gold quality
mucosa of transverse colon	UBERON:0004991	86.86	gold quality
jejunal mucosa	UBERON:0000399	85.84	gold quality
kidney	UBERON:0002113	85.56	gold quality
colonic mucosa	UBERON:0000317	85.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.16	silver quality
duodenum	UBERON:0002114	82.98	gold quality
cortex of kidney	UBERON:0001225	77.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.63	gold quality
transverse colon	UBERON:0001157	77.23	gold quality
small intestine	UBERON:0002108	75.69	gold quality
tibialis anterior	UBERON:0001385	74.21	silver quality
metanephros cortex	UBERON:0010533	72.53	gold quality
adult organism	UBERON:0007023	70.16	gold quality
pancreatic ductal cell	CL:0002079	70.07	silver quality
gall bladder	UBERON:0002110	69.83	gold quality
intestine	UBERON:0000160	67.52	gold quality
metanephros	UBERON:0000081	66.20	gold quality
jejunum	UBERON:0002115	65.50	gold quality
large intestine	UBERON:0000059	64.74	gold quality
colon	UBERON:0001155	63.91	gold quality
vermiform appendix	UBERON:0001154	63.80	gold quality
caecum	UBERON:0001153	60.10	gold quality
colonic epithelium	UBERON:0000397	60.06	gold quality
deltoid	UBERON:0001476	59.55	gold quality
renal medulla	UBERON:0000362	57.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	62.16
E-ANND-3	yes	5.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB

miRNA regulators (miRDB)

18 targeting TINAG, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-4278	95.28	65.49	351
HSA-MIR-433-5P	94.67	64.82	99
HSA-MIR-6732-5P	93.97	64.65	422

Literature-anchored findings (GeneRIF, showing 2)

• An hTIN-ag defect may be a potent cause of end-stage renal failure in childhood. (PMID:20157734)
• TINAG mutation as a genetic cause of pectus excavatum. (PMID:31981812)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctss1	ENSDARG00000036940
danio_rerio	tinagl1	ENSDARG00000061231
danio_rerio	ctsbb	ENSDARG00000101051
mus_musculus	Tinag	ENSMUSG00000032357
rattus_norvegicus	Tinag	ENSRNOG00000058120
drosophila_melanogaster	CtsB	FBGN0030521
drosophila_melanogaster	Swim	FBGN0034709
caenorhabditis_elegans		WBGENE00000781
caenorhabditis_elegans		WBGENE00000782
caenorhabditis_elegans		WBGENE00000784
caenorhabditis_elegans		WBGENE00000785
caenorhabditis_elegans	cpz-1	WBGENE00000788
caenorhabditis_elegans	F26E4.3	WBGENE00009158
caenorhabditis_elegans		WBGENE00013072
caenorhabditis_elegans		WBGENE00013076
caenorhabditis_elegans		WBGENE00013764
caenorhabditis_elegans		WBGENE00016300
caenorhabditis_elegans		WBGENE00016306
caenorhabditis_elegans		WBGENE00019314
caenorhabditis_elegans		WBGENE00019986
caenorhabditis_elegans		WBGENE00022189
caenorhabditis_elegans		WBGENE00044760

Paralogs (12): CTSZ (ENSG00000101160), CTSH (ENSG00000103811), CTSC (ENSG00000109861), CTSL (ENSG00000135047), CTSV (ENSG00000136943), TINAGL1 (ENSG00000142910), CTSK (ENSG00000143387), CTSS (ENSG00000163131), CTSB (ENSG00000164733), CTSW (ENSG00000172543), CTSF (ENSG00000174080), CTSO (ENSG00000256043)

Protein

Protein identifiers

Tubulointerstitial nephritis antigen — Q9UJW2 (reviewed: Q9UJW2)

All UniProt accessions (3): Q9UJW2, Q5T466, Q5T471

UniProt curated annotations — full annotation on UniProt →

Function. Mediates adhesion of proximal tubule epithelial cells via integrins alpha3-beta1 and alphaV-beta3. This is a non catalytic peptidase C1 family protein.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Tissue specificity. Expressed in the kidney cortex, small intestine and cornea.

Post-translational modifications. It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus 2 alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.

Miscellaneous. Antibodies against TINAG are found in sera of patients with tubulointerstitial nephritis, a rare autoimmune disorder that causes acute and chronic renal injury. Major isoform.

Similarity. Belongs to the peptidase C1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJW2-1	1, TIN1	yes
Q9UJW2-2	2, TIN2

RefSeq proteins (1): NP_055279* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000668	Peptidase_C1A_C	Domain
IPR001212	Somatomedin_B_dom	Domain
IPR013128	Peptidase_C1A	Family
IPR025661	Pept_asp_AS	Active_site
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF00112

UniProt features (29 total): sequence conflict 8, disulfide bond 6, sequence variant 5, glycosylation site 5, splice variant 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJW2-F1	82.65	0.63

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 (1): 49–50 (cleavage; by furin)

Disulfide bonds (6): 81–95, 81–83, 87–94, 95–102, 63–70, 70–102

Glycosylation sites (5): 38, 175, 314, 360, 455

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): HNF1_Q6, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, chr6p12, RGTTAMWNATT_HNF1_01, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, TGANTCA_AP1_C, HNF1_C, GOCC_BASEMENT_MEMBRANE, HNF1_01, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, NFE2_01, SAFFORD_T_LYMPHOCYTE_ANERGY, GOBP_PROTEOLYSIS, ER_Q6_02, GOMF_PEPTIDASE_ACTIVITY

GO Biological Process (2): proteolysis (GO:0006508), cell adhesion (GO:0007155)

GO Molecular Function (3): nucleotide binding (GO:0000166), cysteine-type endopeptidase activity (GO:0004197), cysteine-type peptidase activity (GO:0008234)

GO Cellular Component (4): basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
cellular process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
endopeptidase activity	1
cysteine-type peptidase activity	1
peptidase activity	1
extracellular matrix	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TINAG	TINF2	Q9BSI4	774
TINAG	TNKS	O95271	661
TINAG	FST	P19883	614
TINAG	LRRC1	Q9BTT6	589
TINAG	GAL3ST4	Q96RP7	485
TINAG	CPO	Q8IVL8	472
TINAG	MRM1	Q6IN84	457
TINAG	PGLYRP1	O75594	452
TINAG	OR5B17	Q8NGF7	435
TINAG	OR5B3	Q8NH48	432
TINAG	SAMD13	Q5VXD3	417
TINAG	SACK1B	Q5T0W9	405
TINAG	TDRD3	Q9H7E2	400
TINAG	TINAGL1	Q9GZM7	399
TINAG	LRIG2	O94898	388

IntAct

6 interactions, top by confidence:

A	B	Type	Score
NEDD9	RHEB	psi-mi:“MI:0914”(association)	0.530
TINAG	CPB2	psi-mi:“MI:0915”(physical association)	0.370
TINAG	TMEM45B	psi-mi:“MI:0915”(physical association)	0.370
TSHB	SMCHD1	psi-mi:“MI:0914”(association)	0.350
TINAG	VPS26A	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): TYW3 (Affinity Capture-MS), NUDT6 (Affinity Capture-MS), EPDR1 (Affinity Capture-MS), TINAG (Affinity Capture-MS), ACAD11 (Affinity Capture-MS), MOCS1 (Affinity Capture-MS), CTU2 (Affinity Capture-MS), TINAG (Affinity Capture-MS), STK40 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), ZNF696 (Affinity Capture-MS), IDE (Affinity Capture-MS), CTU1 (Affinity Capture-MS), ZNF579 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A1A4K5, A2VDP5, A8K7I4, J3SBP3, J3SEZ3, O14638, P06802, P0DQQ4, P15396, P18563, P18564, P22413, P54793, P97259, P97675, Q08834, Q09328, Q13822, Q14CN2, Q1RPR6, Q29444, Q2TU62, Q32KH8, Q3SZI1, Q4FZV0, Q5FYA8, Q5GF25, Q5R5M5, Q64610, Q6AYF4, Q6DDW2, Q6DYE8, Q6NXH2, Q6PT52, Q6Q473, Q863C4, Q8BTJ4, Q8K1B9, Q8K2I4

Diamond homologs: A0A0F7G352, A0E358, A1E295, F4HVZ1, G5EGP8, O46427, O60911, O97578, P00787, P05167, P05993, P07688, P07711, P07858, P09668, P0DO76, P10605, P19092, P25774, P25778, P25792, P25793, P25802, P25807, P32954, P36400, P43157, P43233, P43507, P43508, P43509, P43510, P49935, P53634, P81494, P83205, P90850, P92131, P92132, P92133

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2077 predictions. Top by Δscore:

Variant	Effect	Δscore
6:54326913:GACA:G	donor_gain	1.0000
6:54326917:G:GG	donor_gain	1.0000
6:54343350:G:GG	donor_gain	1.0000
6:54349705:A:AG	acceptor_gain	1.0000
6:54349706:T:G	acceptor_gain	1.0000
6:54349711:CATA:C	acceptor_loss	1.0000
6:54349712:ATAG:A	acceptor_loss	1.0000
6:54349713:T:G	acceptor_gain	1.0000
6:54349714:A:AG	acceptor_gain	1.0000
6:54349714:AGACT:A	acceptor_gain	1.0000
6:54349715:G:GA	acceptor_gain	1.0000
6:54349715:GA:G	acceptor_gain	1.0000
6:54349715:GAC:G	acceptor_gain	1.0000
6:54349715:GACT:G	acceptor_gain	1.0000
6:54349715:GACTG:G	acceptor_gain	1.0000
6:54349893:CAAC:C	donor_gain	1.0000
6:54349893:CAACG:C	donor_loss	1.0000
6:54349894:AAC:A	donor_gain	1.0000
6:54349895:AC:A	donor_gain	1.0000
6:54349896:CGTA:C	donor_loss	1.0000
6:54349897:G:GG	donor_gain	1.0000
6:54349897:GTAA:G	donor_loss	1.0000
6:54349898:T:A	donor_loss	1.0000
6:54351394:CAAG:C	donor_loss	1.0000
6:54351397:GGT:G	donor_loss	1.0000
6:54351399:T:A	donor_loss	1.0000
6:54354511:A:AG	acceptor_gain	1.0000
6:54354512:G:GG	acceptor_gain	1.0000
6:54354512:GCC:G	acceptor_gain	1.0000
6:54354635:GG:G	donor_gain	1.0000

AlphaMissense

3148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:54347382:G:C	R255P	0.999
6:54349732:T:C	C306R	0.998
6:54349733:G:A	C306Y	0.998
6:54349828:T:A	C338S	0.998
6:54349828:T:C	C338R	0.998
6:54349829:G:C	C338S	0.998
6:54389808:G:C	W438C	0.998
6:54389808:G:T	W438C	0.998
6:54349733:G:T	C306F	0.997
6:54349734:C:G	C306W	0.997
6:54351392:T:A	V374D	0.997
6:54354624:T:A	V413D	0.997
6:54389802:T:A	N436K	0.997
6:54389802:T:G	N436K	0.997
6:54389806:T:A	W438R	0.997
6:54389806:T:C	W438R	0.997
6:54389820:G:C	W442C	0.997
6:54389820:G:T	W442C	0.997
6:54343331:T:A	W244R	0.996
6:54343331:T:C	W244R	0.996
6:54347372:G:C	A252P	0.996
6:54347373:C:A	A252D	0.996
6:54347375:G:C	A253P	0.996
6:54347495:T:A	W293R	0.996
6:54347495:T:C	W293R	0.996
6:54349732:T:A	C306S	0.996
6:54349733:G:C	C306S	0.996
6:54349829:G:A	C338Y	0.996
6:54349830:T:G	C338W	0.996
6:54343312:A:C	Q237H	0.995

dbSNP variants (sampled 300 via entrez): RS1000004946 (6:54388683 T>C), RS1000033785 (6:54334214 G>T), RS1000106711 (6:54334528 A>G), RS1000131525 (6:54352202 T>C,G), RS1000178297 (6:54355625 G>A,T), RS1000247709 (6:54387198 C>G), RS1000260243 (6:54373513 T>C), RS1000299733 (6:54323986 T>C), RS1000305850 (6:54357606 T>A,C), RS1000411605 (6:54361214 G>A), RS1000465947 (6:54341719 A>G), RS1000483214 (6:54355415 C>A), RS1000502307 (6:54372215 C>A,T), RS1000503861 (6:54388469 A>G), RS1000563819 (6:54384145 T>C,G)

Disease associations

OMIM: gene MIM:606749 | 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
GCST000823_11	Radiation response	4.000000e-07
GCST004033_11	QRS interval (sulfonylurea treatment interaction)	3.000000e-07
GCST007565_92	Morning person	6.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007922	response to sulfonylurea
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Zoledronic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
sodium arsenite	affects expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Cidofovir	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	affects expression	1
Valproic Acid	decreases methylation	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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