PGPEP1L

Summary

PGPEP1L (pyroglutamyl-peptidase I like, HGNC:27080) is a protein-coding gene on chromosome 15q26.3, encoding Pyroglutamyl-peptidase 1-like protein (A6NFU8).

Predicted to enable pyroglutamyl-peptidase activity. Predicted to be involved in proteolysis. Predicted to be located in cytosol.

Source: NCBI Gene 145814 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 69 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001167902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27080
Approved symbol	PGPEP1L
Name	pyroglutamyl-peptidase I like
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183571
Ensembl biotype	protein_coding
Entrez	145814

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000378919, ENST00000535714, ENST00000637120, ENST00000905128, ENST00000905129, ENST00000960581, ENST00000960582, ENST00000960583, ENST00000960584, ENST00000960585, ENST00000960586, ENST00000960587

RefSeq mRNA: 4 — MANE Select: NM_001167902 NM_001102612, NM_001167902, NM_001412129, NM_001412130

CCDS: CCDS53977, CCDS58400

Canonical transcript exons

ENST00000535714 — 5 exons

Exon	Start	End
ENSE00001297418	99005429	99005656
ENSE00001479257	98968229	98968697
ENSE00002299533	99007359	99007792
ENSE00003500396	98971036	98971158
ENSE00003682074	98969425	98969651

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 86.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2744 / max 59.2353, expressed in 75 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151753	0.1542	39
151749	0.0597	28
151750	0.0187	7
151748	0.0160	7
151752	0.0152	7
151751	0.0105	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue	UBERON:0001134	86.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.77	gold quality
gastrocnemius	UBERON:0001388	86.00	gold quality
muscle of leg	UBERON:0001383	85.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.88	gold quality
muscle tissue	UBERON:0002385	76.10	gold quality
popliteal artery	UBERON:0002250	71.45	gold quality
tibial artery	UBERON:0007610	71.42	gold quality
right atrium auricular region	UBERON:0006631	70.45	gold quality
right coronary artery	UBERON:0001625	69.82	gold quality
left coronary artery	UBERON:0001626	66.87	gold quality
heart	UBERON:0000948	65.44	gold quality
heart left ventricle	UBERON:0002084	63.63	gold quality
ascending aorta	UBERON:0001496	61.44	gold quality
thoracic aorta	UBERON:0001515	61.15	gold quality
descending thoracic aorta	UBERON:0002345	58.99	gold quality
testis	UBERON:0000473	58.55	gold quality
right testis	UBERON:0004534	58.28	gold quality
left testis	UBERON:0004533	58.13	gold quality
apex of heart	UBERON:0002098	57.28	gold quality
lower esophagus mucosa	UBERON:0035834	56.80	gold quality
nucleus accumbens	UBERON:0001882	54.58	gold quality
muscle layer of sigmoid colon	UBERON:0035805	54.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	54.17	gold quality
prefrontal cortex	UBERON:0000451	54.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	53.69	gold quality
frontal cortex	UBERON:0001870	53.33	gold quality
putamen	UBERON:0001874	53.26	gold quality
right frontal lobe	UBERON:0002810	52.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgpep1l	ENSDARG00000041092
mus_musculus	Pgpep1l	ENSMUSG00000030553
rattus_norvegicus	Pgpep1l	ENSRNOG00000070202
drosophila_melanogaster	CG32147	FBGN0047178
caenorhabditis_elegans		WBGENE00008894
caenorhabditis_elegans		WBGENE00008897
caenorhabditis_elegans	M04C9.1	WBGENE00010856
caenorhabditis_elegans	M04C9.2	WBGENE00010857
caenorhabditis_elegans	M04C9.3	WBGENE00010858
caenorhabditis_elegans		WBGENE00012252
caenorhabditis_elegans		WBGENE00018056
caenorhabditis_elegans		WBGENE00018057

Paralogs (1): PGPEP1 (ENSG00000130517)

Protein

Protein identifiers

Pyroglutamyl-peptidase 1-like protein — A6NFU8 (reviewed: A6NFU8)

All UniProt accessions (2): A0A1B0GWH3, A6NFU8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the peptidase C15 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NFU8-1	1	yes
A6NFU8-2	2

RefSeq proteins (4): NP_001096082, NP_001161374, NP_001399058, NP_001399059 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016125	Peptidase_C15-like	Family
IPR036440	Peptidase_C15-like_sf	Homologous_superfamily

Pfam: PF01470

UniProt features (8 total): active site 3, sequence variant 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NFU8-F1	89.13	0.78

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 (3): 65; 127; 146

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_PROTEOLYSIS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, GOMF_PEPTIDASE_ACTIVITY, chr15q26, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR221_3P, MIR222_3P, MIR5701, MIR8070, MIR550A_3P, GSE13229_MATURE_VS_INTMATURE_NKCELL_UP, GSE13306_LAMINA_PROPRIA_VS_SPLEEN_TREG_UP, MIR664B_5P, MIR3147

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (4): cysteine-type peptidase activity (GO:0008234), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), pyroglutamyl-peptidase activity (GO:0016920)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cysteine-type peptidase activity	1
omega peptidase activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGPEP1L	TTC23	Q5W5X9	555
PGPEP1L	STARD5	P59094	528
PGPEP1L	TMEM270	Q6UE05	479
PGPEP1L	PCDHGA10	Q9Y5H3	449
PGPEP1L	ARRDC4	Q8NCT1	441
PGPEP1L	SYNM	O15061	434
PGPEP1L	CRTAP	O75718	381
PGPEP1L	CTDSPL2	Q05D32	370
PGPEP1L	SFTA2	Q6UW10	370
PGPEP1L	ST8SIA2	Q92186	358
PGPEP1L	SPACA1	Q9HBV2	348
PGPEP1L	HSPBAP1	Q96EW2	348
PGPEP1L	FAM237B	A0A1B0GVD1	348
PGPEP1L	PPP1R36	Q96LQ0	343
PGPEP1L	OTUD1	Q5VV17	339

IntAct

0 interactions, top by confidence:

BioGRID (2): PGPEP1L (Cross-Linking-MS (XL-MS)), PGPEP1L (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0S6XGG4, A0A1B5L8S2, A6NFU8, A7VMU5, O24357, O35130, O80831, P06623, P09543, P13233, P16330, P40935, P49295, Q06287, Q07071, Q08BZ4, Q0P464, Q14397, Q1LXS2, Q2NL24, Q40545, Q52L34, Q567W6, Q56XE8, Q5RFD0, Q5XGC5, Q69ZS7, Q6AXM7, Q6KAI0, Q6UB35, Q76IC5, Q7M753, Q84MA1, Q8BH86, Q8IUF1, Q91754, Q91X44, Q969U7, Q99K82, Q9BDB7

Diamond homologs: A6NFU8, O73944, Q76IC5, Q7NHX6, Q9CWB5, Q9ESW8, Q9NXJ5, Q838N8, P42673

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	61
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1526477	GRCh37/hg19 15q26.3(chr15:99439498-99720434)	Pathogenic
564232	GRCh37/hg19 15q26.2-26.3(chr15:98144229-99857338)x1	Likely pathogenic

SpliceAI

780 predictions. Top by Δscore:

Variant	Effect	Δscore
15:98969648:CGAG:C	acceptor_gain	1.0000
15:98969654:G:C	acceptor_gain	1.0000
15:98971032:TTA:T	donor_loss	1.0000
15:98971033:TA:T	donor_loss	1.0000
15:98971034:A:AC	donor_gain	1.0000
15:98971035:C:CC	donor_gain	1.0000
15:98971035:CTTG:C	donor_gain	1.0000
15:99005425:TTA:T	donor_loss	1.0000
15:99005426:TA:T	donor_loss	1.0000
15:99005427:A:AC	donor_gain	1.0000
15:99005428:C:CC	donor_gain	1.0000
15:99005428:CCAG:C	donor_gain	1.0000
15:98968693:CGTAT:C	acceptor_gain	0.9900
15:98968698:C:CC	acceptor_gain	0.9900
15:98969452:TCGAC:T	donor_gain	0.9900
15:98969647:ACGAG:A	acceptor_gain	0.9900
15:98969648:CGAGC:C	acceptor_gain	0.9900
15:98969649:GAG:G	acceptor_gain	0.9900
15:98969650:AG:A	acceptor_gain	0.9900
15:98969650:AGCTG:A	acceptor_loss	0.9900
15:98969651:GC:G	acceptor_loss	0.9900
15:98969652:C:CC	acceptor_gain	0.9900
15:98969652:CT:C	acceptor_loss	0.9900
15:98969653:T:A	acceptor_loss	0.9900
15:98969654:G:GC	acceptor_gain	0.9900
15:98969656:G:GC	acceptor_gain	0.9900
15:98969662:G:T	acceptor_gain	0.9900
15:98971029:CACTT:C	donor_loss	0.9900
15:98971030:ACTTA:A	donor_loss	0.9900
15:98971034:ACTTG:A	donor_gain	0.9900

AlphaMissense

909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:98969601:T:A	E65D	0.958
15:98969601:T:G	E65D	0.958
15:98969553:G:C	F81L	0.920
15:98969553:G:T	F81L	0.920
15:98969555:A:G	F81L	0.920
15:98968635:A:G	I145T	0.911
15:98969565:G:C	D77E	0.902
15:98969565:G:T	D77E	0.902
15:98969611:A:G	I62T	0.898
15:98968629:A:T	V147D	0.895
15:98968635:A:T	I145N	0.895
15:98968675:A:C	Y132D	0.895
15:98969602:T:A	E65V	0.887
15:98969611:A:T	I62N	0.887
15:98969593:C:T	G68D	0.881
15:98969611:A:C	I62S	0.878
15:98969442:A:C	F118L	0.871
15:98969442:A:T	F118L	0.871
15:98969444:A:G	F118L	0.871
15:98968678:A:C	Y131D	0.866
15:98968692:A:T	V126D	0.866
15:98968635:A:C	I145S	0.865
15:98969567:C:G	D77H	0.855
15:98968633:G:C	H146D	0.847
15:98968581:A:G	L163S	0.846
15:98968668:G:A	S134F	0.845
15:98968686:T:A	D128V	0.845
15:98968641:G:T	A143E	0.838
15:98968669:A:G	S134P	0.836
15:98969532:G:C	C88W	0.832

dbSNP variants (sampled 300 via entrez): RS1000050212 (15:98980764 G>A,C,T), RS1000160001 (15:98978530 T>C), RS1000164597 (15:98983144 A>G), RS1000281989 (15:98970530 C>G), RS1000297883 (15:98998427 G>A), RS1000397530 (15:98970218 A>G), RS1000432111 (15:98978861 C>G), RS1000675592 (15:99002307 T>C), RS1000743301 (15:98971763 G>A), RS1000747674 (15:98968673 G>A), RS1000831300 (15:98976060 T>A), RS1000932897 (15:98989796 T>C), RS1001246288 (15:98985029 G>A), RS1001279460 (15:98985061 G>C), RS1001322278 (15:98977774 G>A)

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

3 associations (top):

Study	Trait	p-value
GCST008839_443	Height	7.000000e-13
GCST010726_63	Periventricular white matter hyperintensities	9.000000e-06
GCST90020028_1474	Hip circumference adjusted for BMI	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
butyraldehyde	increases expression	1
abrine	increases expression	1
Silicon Dioxide	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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