REG1A

Summary

REG1A (regenerating family member 1 alpha, HGNC:9951) is a protein-coding gene on chromosome 2p12, encoding Lithostathine-1-alpha (P05451). Might act as an inhibitor of spontaneous calcium carbonate precipitation.

This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III and IV, based on the primary structures of the encoded proteins. This gene encodes a protein that is secreted by the exocrine pancreas. It is associated with islet cell regeneration and diabetogenesis and may be involved in pancreatic lithogenesis. Reg family members REG1B, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication.

Source: NCBI Gene 5967 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_002909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9951
Approved symbol	REG1A
Name	regenerating family member 1 alpha
Location	2p12
Locus type	gene with protein product
Status	Approved
Aliases	PSP, PTP, PSPS, PSPS1
Ensembl gene	ENSG00000115386
Ensembl biotype	protein_coding
OMIM	167770
Entrez	5967

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 retained_intron, 2 protein_coding

ENST00000233735, ENST00000461579, ENST00000485184, ENST00000488524, ENST00000968102

RefSeq mRNA: 1 — MANE Select: NM_002909 NM_002909

CCDS: CCDS1964

Canonical transcript exons

ENST00000233735 — 6 exons

Exon	Start	End
ENSE00000846820	79123148	79123409
ENSE00001332291	79120488	79120514
ENSE00002462605	79122841	79122952
ENSE00003514496	79120816	79120925
ENSE00003537087	79121988	79122125
ENSE00003550649	79121562	79121680

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 36.6460 / max 52918.4717, expressed in 32 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21129	33.1481	32
21128	3.1375	15
21130	0.1196	5
21132	0.0707	5
21131	0.0482	6
202250	0.0411	7
202253	0.0377	5
202252	0.0229	1
202251	0.0202	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.99	gold quality
body of pancreas	UBERON:0001150	99.99	gold quality
type B pancreatic cell	CL:0000169	99.97	gold quality
duodenum	UBERON:0002114	99.91	gold quality
ileal mucosa	UBERON:0000331	99.87	gold quality
jejunal mucosa	UBERON:0000399	99.87	gold quality
pancreas	UBERON:0001264	99.74	gold quality
pancreatic ductal cell	CL:0002079	99.70	gold quality
epithelial cell of pancreas	CL:0000083	99.56	gold quality
pylorus	UBERON:0001166	99.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.42	gold quality
small intestine	UBERON:0002108	97.79	gold quality
gall bladder	UBERON:0002110	97.39	gold quality
cardia of stomach	UBERON:0001162	96.89	gold quality
vermiform appendix	UBERON:0001154	93.55	gold quality
body of stomach	UBERON:0001161	93.13	gold quality
caecum	UBERON:0001153	92.37	gold quality
fundus of stomach	UBERON:0001160	92.22	gold quality
stomach	UBERON:0000945	90.46	gold quality
right uterine tube	UBERON:0001302	87.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.03	gold quality
jejunum	UBERON:0002115	85.98	gold quality
right coronary artery	UBERON:0001625	85.83	gold quality
left uterine tube	UBERON:0001303	85.20	gold quality
apex of heart	UBERON:0002098	84.86	gold quality
lower esophagus mucosa	UBERON:0035834	84.68	gold quality
ectocervix	UBERON:0012249	84.65	gold quality
metanephros cortex	UBERON:0010533	83.31	gold quality
endocervix	UBERON:0000458	82.87	gold quality
right lobe of liver	UBERON:0001114	81.66	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	83147.69
E-GEOD-83139	yes	73499.40
E-GEOD-81547	yes	65319.93
E-HCAD-31	yes	61087.01
E-ENAD-27	yes	56736.61
E-GEOD-125970	yes	12943.74
E-CURD-46	yes	12121.09
E-MTAB-9543	yes	2074.27
E-MTAB-8495	yes	2032.18
E-GEOD-81608	no	1099.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, KLF5, NR0B2, NR3C1, PARP1, PAX3, SP3, SPI1, STAT3, ZNF362

miRNA regulators (miRDB)

24 targeting REG1A, 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-4795-3P	100.00	74.62	4024
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-571	95.38	66.54	671
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 40)

• did not find any association between abnormalities of either reg1 alpha or reg1 beta gene with type 1 diabetes mellitus, fibrocalculous pancreatopathy, or type 2 diabetes mellitus (PMID:11796176)
• Characterization, structural analysis and putative functions. Review. (PMID:12369899)
• The expression of REG gene is closely related to the carcinoma invasiveness of gastric neoplasms. (PMID:14508825)
• REG expression was reported to be an independent predictor of overall gastric adenocarcinoma patient survival (PMID:15022278)
• Reg I alpha protein may play a role in the development of gastric cancers (PMID:15166487)
• Reg I was observed not only in pancreatic acinar cells but also in the duct-like cells and dilated duct cells. Reg I expression was linked to acinar cell dedifferentiation. (PMID:15211106)
• Analysis of the protein in the bile of patients with pancreaticobiliary maljunction/ choledochal cysts (PMID:15628732)
• REG Ialpha gene is inducible by cytokine stimulation and its gene product may function as a mitogenic and/or an antiapoptotic factor in the development of early gastric cancer. (PMID:15765400)
• Damaged heart may be a target for Reg action, and Reg may protect against acute heart stress. (PMID:15778284)
• Polymorphisms in reg1alpha gene, including the regulatory variants singly or in combination with the known mutations in SPINK1 and/or CTSB genes, are not associated with tropical calcific pancreatitis. (PMID:17990360)
• REG Ialpha protein mediated the anti-apoptotic effects of STAT3 signaling in gastric cancer cells by enhancing Akt activation, Bad phosphorylation and Bcl-xL expression (PMID:18024479)
• in patients treated with chemoradiotherapy, 8 of 23 REG I-positive patients showed complete responses to chemoradiotherapy; only 1 of 19 REG I-negatives did so; survival rate among REG I-positive patients was significantly better than REG I-negatives (PMID:18259819)
• REG expression in Barrett’s esophagus. Expression of REG Ialpha was more frequently observed in patients who showed squamous re-epithelialization of Barrett’s esophagus at biopsy sites. (PMID:18289358)
• REG1A is prognostic molecular marker associated with peritoneal carcinomatosis in colorectal cancer and is significantly raised in peritumoral normal tissue compared to mucosa from healthy individuals, suggesting a molecular field effect of secreted REG1A (PMID:18452172)
• The expression of the REG1A gene is closely related to the infiltrating property of primary gastric carcinoma. (PMID:18630596)
• Overexpression of REG1A is associated with breast cancer. (PMID:18781363)
• REG1A enhances chemo- and radiosensitivity in squamous cell esophageal cancer cells. (PMID:19032369)
• Expression of REG Ialpha but not REG IV was an independent predictor of poor outcome in patients with gastric cancer. (PMID:19329938)
• This finding suggests that REG I may act through IL-6 to exert effects on squamous esophageal cancer cell biology. (PMID:20056108)
• REG Ialpha protein may have a pathophysiological role as a biological mediator for immune cell-derived IL-22 in the ulcerative colitis mucosa. (PMID:20065946)
• Upregulation of REG Ialpha accelerates tumor progression in pancreatic cancer with diabetes. (PMID:20099282)
• Raised serum Reg1alpha protein in type 1 and type 2 diabetes and anti-Reg1alpha antibodies in type 1 diabetes, are reported. (PMID:20972946)
• REG 1A and REG 1B were upregulated during amebiasis and may function to protect the intestinal epithelium from parasite-induced apoptosis. (PMID:21586335)
• Regenerating I protein was highly expressed in pure seminoma and in placental-like alkaline phosphatase-positive seminiferous tubules with in situ carcinoma. (PMID:21683984)
• ELISA showed that the serum level of REG1alpha was significantly higher in patients with pancreatic cancer than it was in the normal controls. (PMID:21691750)
• found a significant increase in REG Ialpha in the sera of celiac disease patients when compared with controls (PMID:21867979)
• Regenerating islet-derived 1alpha (Reg-1alpha) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3) receptor. (PMID:22158612)
• Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid arthritis. (PMID:22203215)
• Immunohistochemistry against known cell-type markers on serial sections has localised the expression of REGs to metaplastic Paneth cells (REG1A, REG1B and REG3A) and enteroendocrine cells (REG4), with a marked expansion of expression during inflammation. (PMID:23519454)
• Pancreactic stone protein levels were able to diagnose sepsis in patients admitted to intensive care units. (PMID:23531337)
• Reduced REG1A expression is associated with chemosensitivity in advanced thoracic esophageal squamous cell carcinoma. (PMID:23645481)
• Autoimmunity to REG Ialpha might play a role in the degeneration of minor salivary gland ductal epithelial cells in primary Sjogren’s syndrome. (PMID:23701206)
• PSP/reg and CRP are differentially regulated by HNF1A and HNF4A in maturity-onset diabetes of the young (PMID:23803251)
• Reg family proteins stimulate pancreatic beta cell proliferation. (PMID:24055447)
• The effects of REG IA on AD and SCC cells were different in the in vitro study, and a correlation between REG IA expression and patient prognosis was noted in the in vivo study (PMID:24065141)
• REG Ialpha overexpression is a characteristic ofsessile serrated adenoma/polyps of the colon, which appears to reflect aberration of crypt cell compartmentalization. (PMID:24225137)
• PSP/reg levels were significantly higher in patients with a PELOD score of 12 or higher or in those with multiple organ dysfunction syndrome. Patients who died tended to have higher PSP/reg levels. (PMID:24594294)
• PSP/reg is significantly up-regulated in T2DM patients, and PSP/reg levels are related to the duration of diabetes. (PMID:25234740)
• Collectively, these findings suggest that REG Ialpha activates c-Jun via the JNK and ERK pathway, thereby enhancing radiosensitivity (PMID:25656613)
• the expression of REG Ialpha and REG Ibeta may be upregulated in human beta cells under inflammatory conditions through the JAK/STAT pathway (PMID:25767811)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-125e6.11	ENSDARG00000025783
danio_rerio	zgc:172053	ENSDARG00000038321
danio_rerio	si:dkey-241l7.6	ENSDARG00000041248
danio_rerio	si:dkey-9i23.4	ENSDARG00000051993
danio_rerio	lectin	ENSDARG00000055833
danio_rerio	si:ch211-125e6.5	ENSDARG00000069381
danio_rerio	si:dkey-241l7.3	ENSDARG00000086956
danio_rerio	si:dkey-241l7.5	ENSDARG00000088989
danio_rerio	si:dkey-241l7.4	ENSDARG00000089478
danio_rerio	si:ch211-125e6.12	ENSDARG00000092090
danio_rerio	si:dkey-9i23.5	ENSDARG00000092459
danio_rerio	si:ch211-125e6.14	ENSDARG00000094183
danio_rerio	si:ch211-125e6.13	ENSDARG00000094370
danio_rerio	si:dkey-241l7.2	ENSDARG00000105335
mus_musculus	Reg2	ENSMUSG00000023140
mus_musculus	Reg1	ENSMUSG00000059654
rattus_norvegicus	Reg1a	ENSRNOG00000006486
caenorhabditis_elegans		WBGENE00012621
caenorhabditis_elegans		WBGENE00016912
caenorhabditis_elegans		WBGENE00019328
caenorhabditis_elegans		WBGENE00019914
caenorhabditis_elegans		WBGENE00020585

Paralogs (5): REG4 (ENSG00000134193), REG3G (ENSG00000143954), REG3A (ENSG00000172016), REG1B (ENSG00000172023), CLEC19A (ENSG00000261210)

Protein

Protein identifiers

Lithostathine-1-alpha — P05451 (reviewed: P05451)

Alternative names: Islet cells regeneration factor, Islet of Langerhans regenerating protein, Pancreatic stone protein, Pancreatic thread protein, Regenerating islet-derived protein 1-alpha, Regenerating protein I alpha

All UniProt accessions (1): P05451

UniProt curated annotations — full annotation on UniProt →

Function. Might act as an inhibitor of spontaneous calcium carbonate precipitation. May be associated with neuronal sprouting in brain, and with brain and pancreas regeneration.

Subcellular location. Secreted.

Tissue specificity. In pancreatic acinar cells and, in lower levels, in brain. Enhanced expression of PSP-related transcripts and intraneuronal accumulation of PSP-like proteins is found in brain from Alzheimer disease and Down syndrome patients.

Post-translational modifications. The composition of the O-linked carbohydrate on Thr-27 is complex and varied. In the crystallographic structure, the attached sugar appears to be N-acetylglucosamine, typical of an intracellular protein, rather than N-acetylgalactosamine.

RefSeq proteins (1): NP_002900* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059

UniProt features (24 total): strand 8, sequence conflict 4, helix 4, disulfide bond 3, signal peptide 1, chain 1, domain 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1QDD	X-RAY DIFFRACTION	1.3
1LIT	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05451-F1	90.86	0.79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 23

Disulfide bonds (3): 36–47, 64–162, 137–154

Glycosylation sites (1): 27

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells

MSigDB gene sets: 105 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOMF_GROWTH_FACTOR_ACTIVITY, LEE_LIVER_CANCER_CIPROFIBRATE_DN, PATIL_LIVER_CANCER, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_HORMONE, LEE_LIVER_CANCER_DENA_DN, SANSOM_APC_TARGETS_DN, MODULE_88, chr2p12, LEE_LIVER_CANCER_E2F1_DN

GO Biological Process (4): positive regulation of cell population proliferation (GO:0008284), response to peptide hormone (GO:0043434), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), signal transduction (GO:0007165)

GO Molecular Function (7): growth factor activity (GO:0008083), signaling receptor activity (GO:0038023), peptidoglycan binding (GO:0042834), oligosaccharide binding (GO:0070492), molecular function inhibitor activity (GO:0140678), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
antimicrobial humoral response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
molecular transducer activity	1
glycosaminoglycan binding	1
carbohydrate binding	1
molecular function regulator activity	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REG1A	ZC3H12A	Q5D1E8	889
REG1A	CLPS	P04118	743
REG1A	CLEC1A	Q8NC01	650
REG1A	DEFA6	Q01524	641
REG1A	EXTL3	O43909	639
REG1A	TFF1	P04155	607
REG1A	DEFA5	Q01523	587
REG1A	LYVE1	Q9Y5Y7	469
REG1A	PRSS1	P07477	424
REG1A	PARP1	P09874	423
REG1A	REG3A	Q06141	419
REG1A	MUC12	Q9UKN1	417
REG1A	HIBCH	Q6NVY1	393
REG1A	PSME4	Q14997	392
REG1A	ABCC6	P78420	364

IntAct

8 interactions, top by confidence:

A	B	Type	Score
REG1B	REG1A	psi-mi:“MI:0915”(physical association)	0.560
REG1B	REG1A	psi-mi:“MI:0914”(association)	0.560
REG1A	REG1B	psi-mi:“MI:0914”(association)	0.560
REG1A	NAA25	psi-mi:“MI:0914”(association)	0.530
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
NEK4	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): REG1A (Affinity Capture-MS), REG1A (Affinity Capture-MS), REG1A (Affinity Capture-MS), NAA25 (Affinity Capture-MS), REG1B (Affinity Capture-MS), NAA20 (Affinity Capture-MS), REG1A (Affinity Capture-MS), APP (Reconstituted Complex), RFWD2 (Affinity Capture-Western)

ESM2 similar proteins: A1XXJ9, A7X3X0, A7X3X3, A7X3X8, A7X3Y2, B5U6Y6, D2YVH7, D2YVJ8, D2YVK5, D8VNS6, I7ICN3, O09037, O09049, O93426, O93427, P05451, P0DM38, P10758, P23132, P23807, P25031, P35230, P35231, P42854, P43137, P48304, P81112, P81114, Q06141, Q08731, Q09GJ8, Q09GK0, Q56EB0, Q5FZI6, Q68AX7, Q6TPG9, Q6UW15, Q6X5S0, Q6X5S1, Q6X5S4

Diamond homologs: A1XXJ9, A3FM55, A7X3W1, A7X3W6, A7X3X0, A7X3X3, A7X3X8, A7X3Y2, A7X3Y6, A7X3Z0, A7X3Z4, A7X3Z7, A7X401, A7X406, A7X409, A7X413, B0VXV0, B0VXV1, B5U6Y6, C6JUN9, D1MGU0, D2YVH7, D2YVI2, D2YVJ6, D2YVJ8, D2YVK1, D2YVK5, D2YW40, D8VNS6, I7ICN3, J3S3U6, J3SBP0, O93427, P05451, P07439, P0DL30, P0DM36, P0DM38, P0DM39, P0DM53

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

458 predictions. Top by Δscore:

Variant	Effect	Δscore
2:79121557:TTCA:T	acceptor_loss	1.0000
2:79121558:TCAG:T	acceptor_loss	1.0000
2:79121560:A:AG	acceptor_gain	1.0000
2:79121560:AG:A	acceptor_gain	1.0000
2:79121561:G:GG	acceptor_gain	1.0000
2:79121561:GG:G	acceptor_gain	1.0000
2:79121561:GGC:G	acceptor_gain	1.0000
2:79121561:GGCC:G	acceptor_gain	1.0000
2:79121561:GGCCA:G	acceptor_gain	1.0000
2:79121654:GACC:G	donor_gain	1.0000
2:79121677:AGAT:A	donor_gain	1.0000
2:79121678:GAT:G	donor_gain	1.0000
2:79121678:GATG:G	donor_gain	1.0000
2:79121679:AT:A	donor_gain	1.0000
2:79121681:G:GA	donor_loss	1.0000
2:79121681:G:GG	donor_gain	1.0000
2:79121682:T:G	donor_loss	1.0000
2:79121685:G:GG	donor_gain	1.0000
2:79121691:A:T	donor_gain	1.0000
2:79121983:A:AG	acceptor_gain	1.0000
2:79121987:GCTCT:G	acceptor_gain	1.0000
2:79122127:T:G	donor_loss	1.0000
2:79120511:ACAGG:A	donor_loss	0.9900
2:79120512:CAGG:C	donor_loss	0.9900
2:79120513:AGG:A	donor_loss	0.9900
2:79120514:GGTA:G	donor_loss	0.9900
2:79120515:GTA:G	donor_loss	0.9900
2:79120516:T:A	donor_loss	0.9900
2:79120814:A:AG	acceptor_gain	0.9900
2:79120815:G:GG	acceptor_gain	0.9900

AlphaMissense

1102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:79122891:G:C	W124C	1.000
2:79122891:G:T	W124C	1.000
2:79121668:G:C	W57C	0.999
2:79121668:G:T	W57C	0.999
2:79121675:G:C	A60P	0.999
2:79121994:T:A	C64S	0.999
2:79121995:G:C	C64S	0.999
2:79122101:G:C	W99C	0.999
2:79122101:G:T	W99C	0.999
2:79122852:G:C	W111C	0.999
2:79122852:G:T	W111C	0.999
2:79122858:G:C	W113C	0.999
2:79122858:G:T	W113C	0.999
2:79123161:G:C	W149C	0.999
2:79123161:G:T	W149C	0.999
2:79121995:G:A	C64Y	0.998
2:79121996:C:G	C64W	0.998
2:79122928:T:A	C137S	0.998
2:79122929:G:C	C137S	0.998
2:79123159:T:A	W149R	0.998
2:79123159:T:C	W149R	0.998
2:79123198:T:A	C162S	0.998
2:79123199:G:C	C162S	0.998
2:79121636:T:A	C47S	0.997
2:79121637:G:C	C47S	0.997
2:79122929:G:A	C137Y	0.997
2:79122930:T:G	C137W	0.997
2:79123192:T:C	F160L	0.997
2:79123194:T:A	F160L	0.997
2:79123194:T:G	F160L	0.997

dbSNP variants (sampled 300 via entrez): RS1000656326 (2:79122522 T>C), RS1001324470 (2:79120074 A>G), RS1001969984 (2:79119086 C>A), RS1002022139 (2:79119358 C>T), RS1002645541 (2:79121460 T>C), RS1002734316 (2:79121231 G>A), RS1002958051 (2:79118966 C>A,T), RS1004419952 (2:79120124 T>C), RS1004555432 (2:79123326 TGA>T), RS1004709212 (2:79120409 T>G), RS1004878542 (2:79123844 G>A), RS1005969530 (2:79121435 A>G), RS1006500093 (2:79121254 T>C), RS1006589297 (2:79118531 C>T), RS1006651267 (2:79122232 G>A,C)

Disease associations

OMIM: gene MIM:167770 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): focal segmental glomerulosclerosis (MONDO:0100313), kidney disorder (MONDO:0005240)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002238_2	Contrast sensitivity	1.000000e-07
GCST005951_41	Body mass index	4.000000e-08
GCST006585_326	Blood protein levels	2.000000e-17
GCST009391_55	Metabolite levels	5.000000e-06
GCST010172_14	Idiopathic downbeat nystagmus	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005419	contrast sensitivity measurement
EFO:0004340	body mass index
EFO:0010474	cystathionine measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	increases expression, increases methylation	2
Valproic Acid	decreases methylation, affects cotreatment, decreases expression	2
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
tetrathiomolybdate	increases expression	1
sulindac sulfide	decreases expression	1
caprylic aldehyde	increases methylation	1
pentanal	increases methylation	1
heptanal	increases methylation	1
Benzo(a)pyrene	decreases methylation	1
Hydralazine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease