PERCC1

Summary

PERCC1 (proline and glutamate rich with coiled coil 1, HGNC:52293) is a protein-coding gene on chromosome 16p13.3, encoding Protein PERCC1 (A0A1W2PR82). Plays a critical role in intestinal function.

Predicted to be involved in digestive tract morphogenesis and enteroendocrine cell differentiation. Implicated in congenital diarrhea.

Source: NCBI Gene 105371045 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001365310

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:52293
Approved symbol	PERCC1
Name	proline and glutamate rich with coiled coil 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000284395
Ensembl biotype	protein_coding
OMIM	618656
Entrez	105371045

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000640283

RefSeq mRNA: 1 — MANE Select: NM_001365310 NM_001365310

CCDS: CCDS92081

Canonical transcript exons

ENST00000640283 — 2 exons

Exon	Start	End
ENSE00003803804	1432547	1434441
ENSE00003806394	1431078	1431108

Expression profiles

Bgee: expression breadth broad, 40 present calls, max score 55.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0453 / max 34.3935, expressed in 17 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152097	0.0453	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	55.95	gold quality
body of stomach	UBERON:0001161	55.71	gold quality
stomach	UBERON:0000945	55.40	gold quality
prostate gland	UBERON:0002367	53.27	gold quality
fundus of stomach	UBERON:0001160	52.36	gold quality
sural nerve	UBERON:0015488	51.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	51.10	gold quality
apex of heart	UBERON:0002098	50.75	gold quality
cerebellum	UBERON:0002037	49.84	gold quality
cerebellar cortex	UBERON:0002129	49.84	gold quality
cerebellar hemisphere	UBERON:0002245	49.82	gold quality
stromal cell of endometrium	CL:0002255	48.35	gold quality
ventricular zone	UBERON:0003053	47.05	gold quality
granulocyte	CL:0000094	46.53	silver quality
bone marrow cell	CL:0002092	45.92	gold quality
colonic epithelium	UBERON:0000397	45.91	gold quality
right lobe of thyroid gland	UBERON:0001119	45.91	gold quality
pituitary gland	UBERON:0000007	45.83	gold quality
left lobe of thyroid gland	UBERON:0001120	45.40	gold quality
thyroid gland	UBERON:0002046	45.37	gold quality
skeletal muscle tissue	UBERON:0001134	43.65	gold quality
adenohypophysis	UBERON:0002196	41.90	gold quality
heart left ventricle	UBERON:0002084	41.46	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	40.54	silver quality
bone marrow	UBERON:0002371	40.32	gold quality
placenta	UBERON:0001987	40.11	silver quality
cortical plate	UBERON:0005343	40.05	gold quality
nucleus accumbens	UBERON:0001882	38.75	silver quality
muscle tissue	UBERON:0002385	38.61	gold quality
brain	UBERON:0000955	38.58	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Nonsense mutation in the novel PERCC1 gene as a genetic cause of congenital diarrhea and enteropathy. (PMID:36076104)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Percc1	ENSMUSG00000114245
rattus_norvegicus	Percc1	ENSRNOG00000065484

Protein

Protein identifiers

Protein PERCC1 — A0A1W2PR82 (reviewed: A0A1W2PR82)

Alternative names: Proline and glutamage-rich protein with a coiled coil domain

All UniProt accessions (1): A0A1W2PR82

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in intestinal function. Acts by promoting the development of enteroendocrine cells (EECs) of the gastrointestinal tract and pancreas. It is thereby required for normal enteroendocrine peptide hormone secretion.

Disease relevance. Diarrhea 11, malabsorptive, congenital (DIAR11) [MIM:618662] A disease characterized by severe, life-threatening watery diarrhea associated with generalized malabsorption and a paucity of enteroendocrine cells. DIAR11 is characterized by onset of intractable diarrhea within the first few weeks of life. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_001352239* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR053819	TEADIR3_omega_loop	Conserved_site

Pfam: PF15238

UniProt features (6 total): region of interest 3, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A1W2PR82-F1	64.66	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 13 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_DIGESTIVE_TRACT_MORPHOGENESIS, GOBP_ENTEROENDOCRINE_CELL_DIFFERENTIATION, GOBP_TUBE_MORPHOGENESIS, GOBP_TUBE_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, HP_DIARRHEA, HP_ABNORMAL_INTESTINE_MORPHOLOGY, HP_ABNORMAL_SMALL_INTESTINE_MORPHOLOGY, HP_ABNORMAL_DIGESTIVE_SYSTEM_MORPHOLOGY, HP_VILLOUS_ATROPHY, chr16p13

GO Biological Process (2): enteroendocrine cell differentiation (GO:0035883), digestive tract morphogenesis (GO:0048546)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epithelial cell differentiation	1
tube morphogenesis	1
digestive tract development	1

Protein interactions and networks

STRING

52 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PERCC1	PRKDC	P78527	567
PERCC1	GPR180	Q86V85	269
PERCC1	GCHFR	P30047	248
PERCC1	ACTB	P02570	225
PERCC1	ALB	P02768	224
PERCC1	NR3C2	P08235	224
PERCC1	GAPDH	P00354	223
PERCC1	AGFG1	P52594	215
PERCC1	IGHV4-38-2	P0DP08	213
PERCC1	PXDN	Q92626	203
PERCC1	PXDNL	A1KZ92	203
PERCC1	PECAM1	P16284	200
PERCC1	DCXR	Q7Z4W1	191
PERCC1	INIP	Q9NRY2	187
PERCC1	FGF2	P09038	185

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: A0A1W2PR82, A0A286YDK6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	1
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3255349	NM_001365310.2(PERCC1):c.390C>G (p.Tyr130Ter)	Pathogenic
2582632	NM_001365310.2(PERCC1):c.348C>G (p.Tyr116Ter)	Likely pathogenic
4073527	NM_001365310.2(PERCC1):c.188C>G (p.Ser63Ter)	Likely pathogenic

SpliceAI

5 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1434439:TGCTG:T	donor_gain	0.3900
16:1434419:T:A	acceptor_gain	0.3500
16:1434417:G:GA	acceptor_gain	0.3300
16:1434418:A:AA	acceptor_gain	0.3300
16:1434414:C:CC	acceptor_gain	0.2000

AlphaMissense

1698 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1433226:G:C	R211S	0.996
16:1433226:G:T	R211S	0.996
16:1432858:T:C	F89L	0.995
16:1432860:T:A	F89L	0.995
16:1432860:T:G	F89L	0.995
16:1432859:T:C	F89S	0.994
16:1433242:T:C	F217L	0.993
16:1433244:C:A	F217L	0.993
16:1433244:C:G	F217L	0.993
16:1432894:T:C	F101L	0.992
16:1432896:T:A	F101L	0.992
16:1432896:T:G	F101L	0.992
16:1433125:T:C	F178L	0.991
16:1433127:C:A	F178L	0.991
16:1433127:C:G	F178L	0.991
16:1432880:A:T	D96V	0.990
16:1433225:G:C	R211T	0.990
16:1433299:T:C	F236L	0.990
16:1433301:C:A	F236L	0.990
16:1433301:C:G	F236L	0.990
16:1433243:T:C	F217S	0.989
16:1433300:T:C	F236S	0.988
16:1432871:T:A	I93N	0.987
16:1433225:G:T	R211M	0.987
16:1432891:T:G	Y100D	0.985
16:1433320:T:A	W243R	0.985
16:1433320:T:C	W243R	0.985
16:1433322:G:C	W243C	0.984
16:1433322:G:T	W243C	0.984
16:1432859:T:G	F89C	0.983

dbSNP variants (sampled 300 via entrez): RS1000157574 (16:1434291 T>A,C), RS1000275621 (16:1430729 G>A), RS1000415286 (16:1430935 C>A,G), RS1000456618 (16:1431795 G>A,C,T), RS1000492314 (16:1434237 T>A), RS1001678557 (16:1434325 G>A,T), RS1001912834 (16:1431150 A>G,T), RS1002058701 (16:1432673 C>G,T), RS1002514323 (16:1432110 T>A), RS1003185955 (16:1431948 G>A), RS1003193366 (16:1429384 TAA>T), RS1003221093 (16:1429589 A>G), RS1003898619 (16:1431492 C>T), RS1004066047 (16:1433886 G>A), RS1004069851 (16:1430461 G>C)

Disease associations

OMIM: gene MIM:618656 | disease phenotypes: MIM:618662

GenCC curated gene-disease

Mondo (1): diarrhea 11, malabsorptive, congenital (MONDO:0032857)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002014	Diarrhea
HP:0011473	Villous atrophy

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Niclosamide	increases expression	1

Clinical trials (associated diseases)

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