PDILT

Summary

PDILT (protein disulfide isomerase like, testis expressed, HGNC:27338) is a protein-coding gene on chromosome 16p12.3, encoding Protein disulfide-isomerase-like protein of the testis (Q8N807). Probable redox-inactive chaperone involved in spermatogenesis.

This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has has an N-terminal ER-signal sequence, two thioredoxin (TRX) domains with non-classical Ser-Lys-Gln-Ser and Ser-Lys-Lys-Cys motifs, respectively, two TRX-like domains, and a C-terminal ER-retention sequence. The protein lacks oxidoreductase activity in vitro and probably functions as a chaperone. This gene’s expression appears to be limited to the testis.

Source: NCBI Gene 204474 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 129 total
• MANE Select transcript: NM_174924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27338
Approved symbol	PDILT
Name	protein disulfide isomerase like, testis expressed
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PDIA7
Ensembl gene	ENSG00000169340
Ensembl biotype	protein_coding
OMIM	618588
Entrez	204474

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000302451, ENST00000575561

RefSeq mRNA: 1 — MANE Select: NM_174924 NM_174924

CCDS: CCDS10584

Canonical transcript exons

ENST00000302451 — 12 exons

Exon	Start	End
ENSE00001143197	20360568	20360657
ENSE00001143206	20362404	20362582
ENSE00001143224	20365420	20365540
ENSE00001258511	20369492	20369689
ENSE00001258516	20372802	20372927
ENSE00001258528	20373012	20373122
ENSE00001258536	20374822	20374959
ENSE00001258543	20376068	20376201
ENSE00001258562	20359175	20359567
ENSE00001304204	20399099	20399307
ENSE00001369072	20404496	20404737
ENSE00003787367	20384645	20384851

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 81.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0193 / max 25.2608, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156689	0.0140	3
156688	0.0053	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	81.97	gold quality
right testis	UBERON:0004534	81.72	gold quality
body of stomach	UBERON:0001161	81.17	gold quality
testis	UBERON:0000473	79.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.70	gold quality
stomach	UBERON:0000945	75.38	gold quality
sperm	CL:0000019	72.18	gold quality
cardia of stomach	UBERON:0001162	71.74	gold quality
fundus of stomach	UBERON:0001160	70.90	gold quality
buccal mucosa cell	CL:0002336	52.31	gold quality
lower esophagus mucosa	UBERON:0035834	46.59	silver quality
colonic epithelium	UBERON:0000397	45.80	gold quality
substantia nigra pars reticulata	UBERON:0001966	45.77	gold quality
synovial joint	UBERON:0002217	44.23	gold quality
subthalamic nucleus	UBERON:0001906	43.97	gold quality
adult organism	UBERON:0007023	43.79	gold quality
amniotic fluid	UBERON:0000173	43.78	gold quality
duodenum	UBERON:0002114	43.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
medulla oblongata	UBERON:0001896	43.23	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
middle temporal gyrus	UBERON:0002771	42.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	41.86	gold quality
sural nerve	UBERON:0015488	41.76	gold quality
superior vestibular nucleus	UBERON:0007227	41.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.69	gold quality
substantia nigra pars compacta	UBERON:0001965	41.54	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
esophagus squamous epithelium	UBERON:0006920	41.41	gold quality
trigeminal ganglion	UBERON:0001675	41.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting PDILT, 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-3162-3P	100.00	65.37	363
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-1322	97.98	68.96	625

Literature-anchored findings (GeneRIF, showing 3)

• The expression of PDILT, in addition to PDI in the testis, suggests that PDILT performs a specialized chaperone function in testicular cells. (PMID:15475357)
• Further studies of this recently discovered PDI member would help to understand the important role that PDILT plays in the differentiation and maturation of spermatozoids. (PMID:24662985)
• indings have identified the critical regions and conformational changes of PDILT that enable and control its activity. These results advance our understanding of the structural mechanisms involved in the chaperone activity of PDILT. (PMID:29203529)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdia8	ENSDARG00000033599
danio_rerio	zgc:136472	ENSDARG00000058445
mus_musculus	Pdilt	ENSMUSG00000030968
rattus_norvegicus	Pdilt	ENSRNOG00000015368
drosophila_melanogaster	ERp60	FBGN0033663
drosophila_melanogaster	Tmx3	FBGN0036579
drosophila_melanogaster	Pdi	FBGN0286818
caenorhabditis_elegans		WBGENE00003962
caenorhabditis_elegans		WBGENE00003963
caenorhabditis_elegans	pdi-3	WBGENE00003964
caenorhabditis_elegans	M04D5.1	WBGENE00014807
caenorhabditis_elegans	ZK973.11	WBGENE00022836

Paralogs (13): ERP44 (ENSG00000023318), PDIA5 (ENSG00000065485), TMX4 (ENSG00000125827), ERP27 (ENSG00000139055), TMX1 (ENSG00000139921), PDIA6 (ENSG00000143870), TXNDC11 (ENSG00000153066), PDIA4 (ENSG00000155660), TMX3 (ENSG00000166479), PDIA3 (ENSG00000167004), PDIA2 (ENSG00000185615), P4HB (ENSG00000185624), TXNDC5 (ENSG00000239264)

Protein

Protein identifiers

Protein disulfide-isomerase-like protein of the testis — Q8N807 (reviewed: Q8N807)

All UniProt accessions (2): Q8N807, I3L1W7

UniProt curated annotations — full annotation on UniProt →

Function. Probable redox-inactive chaperone involved in spermatogenesis.

Subunit / interactions. Homodimer. The homodimer is not disulfide-linked. Interacts with ERO1A and CLGN.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Testis-specific.

Post-translational modifications. N-glycosylated.

Domain organisation. The thioredoxin domain lacks the conserved redox-active Cys at position 417 which is replaced by a Ser residue, suggesting that it lacks thioredoxin activity.

Similarity. Belongs to the protein disulfide isomerase family.

RefSeq proteins (1): NP_777584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013766	Thioredoxin_domain	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF00085, PF13848

UniProt features (66 total): helix 23, strand 18, sequence variant 7, turn 6, glycosylation site 5, mutagenesis site 2, signal peptide 1, chain 1, sequence conflict 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4NWY	X-RAY DIFFRACTION	2
5XF7	X-RAY DIFFRACTION	2.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N807-F1	85.18	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.

Glycosylation sites (5): 58, 128, 160, 340, 540

Mutagenesis-validated functional residues (2):

Position	Phenotype
135	does not affect homodimerization; when associated with a-420.
420	does not affect homodimerization; when associated with a-135.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_PROTEIN_MATURATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_PROTEIN_FOLDING, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr16p12, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY, GOMF_PROTEIN_DISULFIDE_ISOMERASE_ACTIVITY, GOMF_PROTEIN_FOLDING_CHAPERONE, GSE10239_NAIVE_VS_KLRG1INT_EFF_CD8_TCELL_DN, MIR875_3P, BDP1_TARGET_GENES, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_24H_ACT_CD4_TCELL_UP, GOBP_SEXUAL_REPRODUCTION

GO Biological Process (5): protein folding (GO:0006457), spermatid development (GO:0007286), primordial germ cell migration (GO:0008354), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (3): protein disulfide isomerase activity (GO:0003756), protein folding chaperone (GO:0044183), isomerase activity (GO:0016853)

GO Cellular Component (1): endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
germ cell development	1
spermatid differentiation	1
gamete generation	1
cell migration	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
intramolecular oxidoreductase activity, transposing S-S bonds	1
catalytic activity, acting on a protein	1
molecular_function	1
protein folding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1091 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDILT	CALR3	Q96L12	697
PDILT	PRSS37	A4D1T9	671
PDILT	CLGN	O14967	659
PDILT	RNASE10	Q5GAN6	628
PDILT	MAGEB2	O15479	608
PDILT	TPST2	O60704	598
PDILT	UMOD	P07911	577
PDILT	ADAM2	P78326	574
PDILT	PRSS55	Q6UWB4	547
PDILT	TEX101	Q9BY14	545
PDILT	TGM4	P49221	512
PDILT	CBLIF	P27352	499
PDILT	TAF1D	Q9H5J8	476
PDILT	LY6K	Q17RY6	474
PDILT	DENND4A	Q7Z401	466

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PDILT	ITIH2	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): SERPINB4 (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), RABL6 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1N5Y4, A3KPF5, D7SFH9, O13811, O44342, P12865, P32474, P38658, P52588, Q0E0I1, Q0JD42, Q10057, Q17688, Q32L47, Q43116, Q498R3, Q4N4N8, Q53LQ0, Q54EN4, Q5FVM7, Q5R5L3, Q5RCM7, Q5WA72, Q5XI02, Q5ZKZ4, Q66GQ3, Q67IX6, Q69ST6, Q6AUC6, Q6NRT6, Q6P5E4, Q7XRB5, Q8IXB1, Q8N807, Q8VX13, Q8VZQ0, Q8W4J3, Q94F09, Q95LM0, Q96DN0

Diamond homologs: D3Z6P0, D4B2L8, O13704, O13811, O22263, O48773, O51890, P00275, P04785, P05307, P07237, P08003, P09102, P09103, P0A617, P0AGG4, P0AGG5, P0AGG6, P0AGG7, P10473, P11598, P13667, P21195, P23400, P27773, P29828, P30101, P34329, P38657, P38659, P38660, P38661, P46843, P52230, P52233, P52588, P52589, P54399, P55059, P73263

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1796 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20359564:ACAG:A	acceptor_gain	1.0000
16:20359565:CAG:C	acceptor_gain	1.0000
16:20359565:CAGC:C	acceptor_gain	1.0000
16:20359566:AG:A	acceptor_gain	1.0000
16:20359567:GCT:G	acceptor_loss	1.0000
16:20359568:C:CC	acceptor_gain	1.0000
16:20360562:CCTTA:C	donor_loss	1.0000
16:20360563:CTTA:C	donor_loss	1.0000
16:20360564:TTA:T	donor_loss	1.0000
16:20360565:TA:T	donor_loss	1.0000
16:20360566:A:AC	donor_gain	1.0000
16:20360566:A:AT	donor_loss	1.0000
16:20360567:C:CC	donor_gain	1.0000
16:20360567:CCT:C	donor_gain	1.0000
16:20360654:CAGC:C	acceptor_gain	1.0000
16:20360658:CTA:C	acceptor_loss	1.0000
16:20360659:T:G	acceptor_loss	1.0000
16:20362402:A:AC	donor_gain	1.0000
16:20362403:C:CC	donor_gain	1.0000
16:20373121:CCCT:C	acceptor_gain	1.0000
16:20373122:CCTTG:C	acceptor_gain	1.0000
16:20373124:T:C	acceptor_gain	1.0000
16:20373124:T:TC	acceptor_gain	1.0000
16:20399097:A:AC	donor_gain	1.0000
16:20399098:C:CC	donor_gain	1.0000
16:20399379:T:TA	donor_gain	1.0000
16:20359563:AACAG:A	acceptor_gain	0.9900
16:20359570:A:AC	acceptor_gain	0.9900
16:20359570:A:C	acceptor_gain	0.9900
16:20359577:C:CT	acceptor_gain	0.9900

AlphaMissense

3895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20362492:G:T	A443D	0.984
16:20362493:C:G	A443P	0.984
16:20365428:A:T	V410E	0.983
16:20384686:A:G	L123P	0.978
16:20376172:A:G	W147R	0.977
16:20376172:A:T	W147R	0.977
16:20365482:A:T	L392H	0.976
16:20369532:A:G	L359P	0.975
16:20376162:C:G	R150P	0.975
16:20376078:C:T	G178D	0.973
16:20384758:C:T	G99D	0.971
16:20399143:A:G	L53P	0.969
16:20376079:C:G	G178R	0.967
16:20374835:A:G	L223P	0.966
16:20374894:A:C	F203L	0.963
16:20374894:A:T	F203L	0.963
16:20374896:A:G	F203L	0.963
16:20362426:A:G	L465P	0.960
16:20369601:A:T	V336D	0.960
16:20374892:C:T	G204E	0.960
16:20384683:A:G	F124S	0.960
16:20399113:A:G	L63P	0.959
16:20365431:A:G	F409S	0.958
16:20365482:A:G	L392P	0.958
16:20372881:A:G	L280P	0.956
16:20399115:G:C	F62L	0.956
16:20399115:G:T	F62L	0.956
16:20399117:A:G	F62L	0.956
16:20374838:A:T	V222D	0.955
16:20399100:G:C	F67L	0.955

dbSNP variants (sampled 300 via entrez): RS1000040458 (16:20380987 G>A), RS1000061660 (16:20361479 C>T), RS1000105930 (16:20394317 C>T), RS1000110471 (16:20360292 T>G), RS1000126809 (16:20366938 T>C), RS1000139628 (16:20398650 C>T), RS1000185965 (16:20370729 A>G,T), RS1000192736 (16:20361463 G>A,C), RS1000204527 (16:20383803 T>G), RS1000245301 (16:20360569 T>G), RS1000269416 (16:20389549 T>A), RS1000291124 (16:20366781 G>A,T), RS1000306053 (16:20383533 G>A,C), RS1000360532 (16:20377022 A>G), RS1000367519 (16:20378389 TCTC>T)

Disease associations

OMIM: gene MIM:618588 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST000649_18	Chronic kidney disease	1.000000e-20
GCST002376_1	Urinary uromodulin levels	6.000000e-27
GCST002376_5	Urinary uromodulin levels	4.000000e-15
GCST002720_1	Kidney function decline traits	2.000000e-17
GCST002720_6	Kidney function decline traits	8.000000e-13
GCST002720_7	Kidney function decline traits	9.000000e-08
GCST002720_8	Kidney function decline traits	4.000000e-06
GCST003790_11	Glomerular filtration rate	2.000000e-15
GCST003790_5	Glomerular filtration rate	4.000000e-07
GCST003790_6	Glomerular filtration rate	2.000000e-09
GCST005984_40	Glomerular filtration rate	6.000000e-59
GCST005985_56	Creatinine levels	2.000000e-53
GCST005986_22	Blood urea nitrogen levels	7.000000e-29
GCST006190_84	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-08
GCST006191_2	Diastolic blood pressure x smoking status (ever vs never) interaction (1df test)	2.000000e-08
GCST007094_91	Diastolic blood pressure	2.000000e-09
GCST007344_13	Estimated glomerular filtration rate	4.000000e-20
GCST007344_16	Estimated glomerular filtration rate	3.000000e-83
GCST007344_58	Estimated glomerular filtration rate	7.000000e-06
GCST007344_84	Estimated glomerular filtration rate	3.000000e-09
GCST007833_10	Urolithiasis	9.000000e-11
GCST007877_17	Creatinine levels	2.000000e-16
GCST007927_31	Medication use (beta blocking agents)	7.000000e-11
GCST007928_3	Medication use (diuretics)	1.000000e-11
GCST007930_102	Medication use (agents acting on the renin-angiotensin system)	7.000000e-17
GCST008058_189	Estimated glomerular filtration rate	3.000000e-259
GCST008059_102	Estimated glomerular filtration rate	1.000000e-213
GCST008060_31	Estimated glomerular filtration rate	1.000000e-37
GCST008062_8	Blood urea nitrogen levels	5.000000e-42
GCST008064_26	Chronic kidney disease	7.000000e-86

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005663	urinary uromodulin measurement
EFO:0006829	GFR change measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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