CHGA

Summary

CHGA (chromogranin A, HGNC:1929) is a protein-coding gene on chromosome 14q32.12, encoding Chromogranin-A (P10645). Strongly inhibits glucose induced insulin release from the pancreas.

The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1113 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_001275

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1929
Approved symbol	CHGA
Name	chromogranin A
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	PHE5, PHES
Ensembl gene	ENSG00000100604
Ensembl biotype	protein_coding
OMIM	118910
Entrez	1113

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000216492, ENST00000334654, ENST00000553866, ENST00000556076, ENST00000556098, ENST00000556876, ENST00000903321, ENST00000903322, ENST00000903323, ENST00000903324, ENST00000903325, ENST00000967838, ENST00000967839

RefSeq mRNA: 2 — MANE Select: NM_001275 NM_001275, NM_001301690

CCDS: CCDS76718, CCDS9906

Canonical transcript exons

ENST00000216492 — 8 exons

Exon	Start	End
ENSE00000808703	92924199	92924245
ENSE00001362941	92923150	92923405
ENSE00002466212	92934801	92935285
ENSE00003303855	92932370	92932851
ENSE00003541988	92931250	92931702
ENSE00003546834	92926605	92926698
ENSE00003576154	92929717	92929815
ENSE00003615610	92927550	92927618

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 37.2262 / max 8109.9905, expressed in 360 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141156	37.1289	360
141158	0.0973	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.50	gold quality
primary visual cortex	UBERON:0002436	99.48	gold quality
duodenum	UBERON:0002114	99.02	gold quality
superior frontal gyrus	UBERON:0002661	98.96	gold quality
pituitary gland	UBERON:0000007	98.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.13	gold quality
prefrontal cortex	UBERON:0000451	97.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.82	gold quality
rectum	UBERON:0001052	97.78	gold quality
frontal cortex	UBERON:0001870	97.47	gold quality
adenohypophysis	UBERON:0002196	97.35	gold quality
right frontal lobe	UBERON:0002810	96.70	gold quality
cerebral cortex	UBERON:0000956	96.32	gold quality
anterior cingulate cortex	UBERON:0009835	96.27	gold quality
right testis	UBERON:0004534	96.17	gold quality
cortical plate	UBERON:0005343	95.85	gold quality
pancreas	UBERON:0001264	95.64	gold quality
left testis	UBERON:0004533	95.62	gold quality
testis	UBERON:0000473	95.20	gold quality
hypothalamus	UBERON:0001898	94.51	gold quality
mucosa of transverse colon	UBERON:0004991	94.10	gold quality
ganglionic eminence	UBERON:0004023	94.06	gold quality
body of pancreas	UBERON:0001150	93.72	gold quality
telencephalon	UBERON:0001893	92.88	gold quality
body of stomach	UBERON:0001161	92.73	gold quality
stomach	UBERON:0000945	92.67	gold quality
small intestine	UBERON:0002108	91.57	gold quality
Ammon’s horn	UBERON:0001954	91.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.05	gold quality
brain	UBERON:0000955	89.66	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	3603.65
E-MTAB-9154	yes	1688.79
E-MTAB-10283	yes	1477.19
E-CURD-46	yes	1133.36
E-GEOD-134144	yes	398.05
E-CURD-88	yes	152.95
E-MTAB-5061	yes	29.77
E-GEOD-83139	yes	8.42
E-GEOD-125970	yes	6.70
E-HCAD-10	yes	3.89
E-HCAD-31	no	2620.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARX, ASCL1, CREB1, CREM, CTNNB1, EBF1, EGR1, JUN, LEF1, REST, SP1

miRNA regulators (miRDB)

38 targeting CHGA, 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-4534	99.99	66.58	1907
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4433A-3P	97.75	62.82	1435

Literature-anchored findings (GeneRIF, showing 40)

• CGA and CGB were also found to have an immune origin, being present in monocytes and neutrophils during coronary artery bypass surgery, possibly due to raised IL-6 plasma levels. (PMID:12091348)
• CgA may play some role in the early phase of neoplastic progression (PMID:12165659)
• The peptides WE14 and EL35, derived from evolutionarily conserved regions of CHGA, were studied in human endocrine tissues. (PMID:12397377)
• identification of a novel sorting determinant for the regulated pathway (PMID:12432071)
• WE-14 is found in the adrenal chromaffin cell population and in the enterochromaffin-like (ECL) cells of the oxyntic mucosa (PMID:12438141)
• Chromofungin is an antimicrobial peptide with antifungal activity. (PMID:12438152)
• isolation and characterization human CgA-derived peptides produced by endogenous prohormone convertases (PMID:12442257)
• studies for the first time identify Egr-1 as a nuclear target of gastrin and show that functional interplay of Egr-1, Sp1, and CREB is indispensable for gastrin-dependent CgA transactivation in gastric epithelial cells (PMID:12456801)
• differences in CgA and CD57 expression in human neuroendocrine tumors are related to the degree of differentiation of the neoplasms and probably reflect the degree of maturation (functional state) of neuroendocrine granules within the neoplastic cells. (PMID:12687271)
• Immunoreactive patterns of chromogranin A and B [CgA,CgB] were investigated in Creutzfeldt-Jakob disease and Alzheimer’s disease. CgB, but not CgA was selectively associated with prion protein deposits, whereas CgA was only seen in amyloid beta plaques (PMID:12692477)
• expression and localization of chromogranin A (CgA), chromogranin B (CgB), synaptophysin, and insulin were ultrastructurally studied with the immunogold technique in porcine and human pancreatic islet neuroendocrine cells (PMID:12826904)
• Circulating CgA could help regulate the endothelial barrier function and to protect vessels against TNF-induced plasma leakage in pathological conditions characterized by increased production of TNF and CgA, such as cancer or heart failure. (PMID:14734634)
• The relative risk of clinical understaging of prostatic neoplasms significantly varied according to serum CgA levels (PMID:14968443)
• The results indicate that the decrease in the number of CgA positive large dense-core vesicles per terminal, and/or in the number of CgA positive terminals, suggesting possible functional impairment of prefrontal synaptic contact in schizophrenia. (PMID:15337252)
• More chromogranin A was expressed in benign epithelial cells adjacent to adenocarcinomatic lesions than in the adenocarcinoma and in nodular hyperplasia of the prostatic gland. (PMID:15462496)
• V-ATPase-mediated pH gradient in the secretory pathway is an important factor for the formation of dense-core granules by regulating the ability of CgA to form aggregates, a crucial step that may underlie the granulogenic function of the protein. (PMID:15542860)
• In human adrenocortical adenomas CgA is not expressed, and removal of the mass does not modify plasma CgA levels. Endocrine involvement of local CgA in adrenocortical tumorigenesis is unlikely. (PMID:15648545)
• Elevated plasma chromogranin A levels are associated with prostate cancer patients with hormone-refractory disease (PMID:15788643)
• Dysglycemic peptide pancreastatin is active in humans on multiple facets of intermediary metabolism, though is does not antagonize insulin. It is elevated in diabetes, and variant Gly297Ser had increased potency to inhibit glucose uptake. (PMID:15956083)
• Rescue of elevated BP to normalcy was achieved by humanization of Chga mice. (PMID:16007257)
• suggest vasostatins as novel cardioregulatory peptides in mammals (PMID:16151967)
• CgA was detected in secretory granules of serous and ductal cells by immunoelectron microscopy; CgA in humans is produced by HSG and secreted into saliva. (PMID:16330879)
• Commercial CgA antibodies seem more useful for histopathological diagnosis of enterochromaffin-like cell neoplasms than the antibodies to the other CgA regions. (PMID:16408221)
• CgA levels may have a diagnostic, therapeutic and prognostic role in the management of prostate cancer patients. (PMID:16450720)
• These results suggest that the CHGA gene is associated with the risk of developing schizophrenia in the Japanese population. (PMID:16504480)
• trong positive linear relationship exists between serum and plasma CGA levels in pancreatic carcinoid tumor patients. (PMID:17003646)
• propose that CgA promotes the biogenesis of secretory granules by a mechanism involving a granulogenic determinant located within CgA-(40-115) of the mature protein (PMID:17032650)
• The changes in salivary CgA secretion as a result of exposure to a cognitive task may indicate psychological stress in humans. (PMID:17060047)
• Expression of NeuroD1 versus chromogranin-A is more frequent in pCA (PMID:17126478)
• Antiadrenergic effect of vasostatin-1 is mainly due to a phosphatidylinositol 3-kinase dependent nitric oxide release by cardiac endothelial cells. (PMID:17293489)
• Salivary CgA levels peak upon awakening, and then quickly decrease to the nadir after 1 hour and maintained a low level throughout the day. On the other hand, plasma CgA did not show any obvious circadian rhythm. (PMID:17379958)
• CgA is highly expressed in microdissected cells from carcinoid metastases and its promoter controls the adenoviral E1A gene, making it a possible agent for treating liver metastasis. (PMID:17438105)
• common, heritable variation in expression of the human CHGA gene influences endothelial ET-1 secretion in vivo (PMID:17438153)
• The catestatin Gly364Ser variant cleaved from CHAG causes profound changes in human autonomic activity, both parasympathetic and sympathetic, and seems to reduce risk of developing hypertension, especially in men (PMID:17438154)
• chromogranin A salivary levels increase with laughter (PMID:17510497)
• Octreotide suppression test with CgA level assessment in NET patients is a simple, straightforward examination, providing information on the predicted response to the applied SSA and the data on initial clinical tolerance of those agents. (PMID:17578828)
• Increased serum levels of CgA in nonsmall cell lung cancer are independent from protein expression in tumors and more likely related to neuroendocrine response associated with worsening of patient condition. (PMID:17599769)
• These results suggest new roles for secretory protein tertiary structure in hormone and transmitter storage, with implications for secretory cargo condensation (or dense core “packing” structure) within the regulated pathway. (PMID:17718510)
• A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor. (PMID:17889508)
• The finding that PGP 9.5 and ChA are expressed by PC-3 and DU145 cells suggests that these cells may have been derived from metastatic adenocarcinomas which had undergone neuroendocrine differentiation or expression occurred as a result of cell culture. (PMID:17929277)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chga	ENSDARG00000008829
mus_musculus	Chga	ENSMUSG00000021194
rattus_norvegicus	Chga	ENSRNOG00000052549

Paralogs (1): CHGB (ENSG00000089199)

Protein

Protein identifiers

Chromogranin-A — P10645 (reviewed: P10645)

Alternative names: Pituitary secretory protein I

All UniProt accessions (3): P10645, G3V2Q7, G5E968

UniProt curated annotations — full annotation on UniProt →

Function. Strongly inhibits glucose induced insulin release from the pancreas. Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. Displays antibacterial activity against Gram-positive bacteria S.aureus and M.luteus, and Gram-negative bacteria E.coli and P.aeruginosa. Can induce mast cell migration, degranulation and production of cytokines and chemokines. Acts as a potent scavenger of free radicals in vitro. May play a role in the regulation of cardiac function and blood pressure. Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation.

Subunit / interactions. Self-interacts; self-assembly is promoted in vitro by chondroitin sulfate attachment which occurs at mildly acidic pH conditions. Interacts with SCG3. Interacts with ITPR1 in the secretory granules.

Subcellular location. Secreted. Cytoplasmic vesicle. Secretory vesicle Cytoplasmic vesicle. Secretory vesicle. Neuronal dense core vesicle.

Tissue specificity. Detected in cerebrospinal fluid (at protein level). Detected in urine (at protein level). Found in the brain.

Post-translational modifications. Sulfated on tyrosine residues and/or contains sulfated glycans. O-glycosylated with core 1 or possibly core 8 glycans. Contains chondroitin sulfate (CS); CS attachment is pH-dependent, being observed at mildly acidic conditions of pH 5 but not at neutral pH, and promotes self-assembly in vitro. Proteolytic processing gives rise to an additional longer form of catestatin (residues 358-390) which displays a less potent catecholamine release-inhibitory activity. Plasmin-mediated proteolytic processing can give rise to additional shorter and longer forms of catestatin peptides.

Miscellaneous. Binds calcium with a low-affinity.

Similarity. Belongs to the chromogranin/secretogranin protein family.

RefSeq proteins (2): NP_001266, NP_001288619 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001819	Chromogranin_AB	Family
IPR001990	Granin	Family
IPR018054	Chromogranin_CS	Conserved_site

Pfam: PF01271

UniProt features (81 total): peptide 18, modified residue 16, sequence conflict 14, sequence variant 12, compositionally biased region 8, glycosylation site 4, region of interest 3, strand 2, signal peptide 1, chain 1, disulfide bond 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1LV4	SOLUTION NMR
6R2X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10645-F1	59.33	0.15

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 (16): 142, 194, 203, 218, 270, 300, 319, 322, 333, 371, 372, 398, 402, 424, 438, 456

Disulfide bonds (1): 35–56

Glycosylation sites (4): 181, 183, 251, 424

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 253 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOCC_SECRETORY_GRANULE, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_RELAXATION_OF_CARDIAC_MUSCLE, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (19): regulation of the force of heart contraction (GO:0002026), mast cell chemotaxis (GO:0002551), regulation of blood pressure (GO:0008217), killing of cells of another organism (GO:0031640), protein localization to secretory granule (GO:0033366), negative regulation of catecholamine secretion (GO:0033604), defense response to bacterium (GO:0042742), mast cell degranulation (GO:0043303), innate immune response (GO:0045087), mast cell activation (GO:0045576), negative regulation of insulin secretion (GO:0046676), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), defense response to fungus (GO:0050832), positive regulation of cardiac muscle contraction (GO:0060452), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway (GO:1900738), positive regulation of relaxation of cardiac muscle (GO:1901899), positive regulation of dense core granule biogenesis (GO:2000707)

GO Molecular Function (0):

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), transport vesicle (GO:0030133), secretory granule (GO:0030141), chromaffin granule (GO:0042583), perinuclear region of cytoplasm (GO:0048471), neuronal dense core vesicle (GO:0098992), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of biological quality	2
defense response	2
defense response to bacterium	2
cellular anatomical structure	2
endomembrane system	2
cytoplasm	2
regulation of heart contraction	1
leukocyte chemotaxis	1
mast cell migration	1
blood circulation	1
cell killing	1
disruption of cell in another organism	1
protein localization to organelle	1
catecholamine secretion	1
regulation of catecholamine secretion	1
negative regulation of amine transport	1
negative regulation of secretion by cell	1
response to bacterium	1
mast cell activation involved in immune response	1
mast cell mediated immunity	1
lysosome localization	1
leukocyte degranulation	1
establishment of organelle localization	1
immune response	1
defense response to symbiont	1
myeloid leukocyte activation	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
response to fungus	1
positive regulation of heart contraction	1
positive regulation of striated muscle contraction	1
regulation of cardiac muscle contraction	1
cardiac muscle contraction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
adrenergic receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of G protein-coupled receptor signaling pathway	1
regulation of phospholipase C-activating G protein-coupled receptor signaling pathway	1

Protein interactions and networks

STRING

2180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHGA	SCG3	Q8WXD2	985
CHGA	CHGB	P05060	978
CHGA	ENO2	P09104	939
CHGA	SCG2	P13521	939
CHGA	SYP	P08247	918
CHGA	SST	P01166	868
CHGA	CPE	P16870	853
CHGA	GAST	P01350	840
CHGA	GCG	P01275	821
CHGA	NCAM1	P13591	815
CHGA	KRT20	P35900	771
CHGA	SCG5	P01164	762
CHGA	GRP	P07491	739
CHGA	LGR5	O75473	734
CHGA	KRT7	P08729	729

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CHGA	DENR	psi-mi:“MI:0914”(association)	0.530
CHGA	CDC37	psi-mi:“MI:0915”(physical association)	0.370
CHGA	NEK2	psi-mi:“MI:0915”(physical association)	0.370
PFDN1	CHGA	psi-mi:“MI:0915”(physical association)	0.370
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CHGA (Affinity Capture-MS), SAPCD2 (Affinity Capture-MS), CCDC101 (Affinity Capture-MS), DENR (Affinity Capture-MS), CHGA (Affinity Capture-Western), CHGA (Biochemical Activity), SAPCD2 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), DENR (Affinity Capture-MS), XPNPEP3 (Affinity Capture-MS), CHGA (Affinity Capture-MS), CHGA (Two-hybrid), CHGA (Two-hybrid), CHGA (Two-hybrid), CHGA (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2BDC9, A2VD12, A4IFM1, B5X1Q3, B5X216, B6ZI38, O14836, O35181, O60279, O75128, O77559, P05059, P07141, P09603, P0C8S2, P10354, P10645, P13085, P24054, P26339, P56975, P58073, P97297, Q3TVI8, Q3USH1, Q4V9H3, Q4W8E7, Q5FVQ7, Q5R5B8, Q673G8, Q6PAL1, Q6QZN6, Q6ZSG2, Q80XI1, Q8CAE9, Q8JZQ0, Q8K201, Q8NBI3

Diamond homologs: P04404, P05059, P10354, P10645, P26339, P33716, Q9XS63

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	CHGA	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	CHGA	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	CHGA	“transcriptional regulation”
CHGA	up-regulates	Secretory_granule_organization
CHGA	up-regulates	Peptide_hormone_processing

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1082 predictions. Top by Δscore:

Variant	Effect	Δscore
14:92929714:CAGG:C	acceptor_loss	1.0000
14:92929715:A:AG	acceptor_gain	1.0000
14:92929715:AGG:A	acceptor_loss	1.0000
14:92929716:G:GT	acceptor_gain	1.0000
14:92929716:GGC:G	acceptor_gain	1.0000
14:92929812:AAAG:A	donor_loss	1.0000
14:92929815:GG:G	donor_loss	1.0000
14:92929816:GTCT:G	donor_loss	1.0000
14:92923402:CAAGG:C	donor_loss	0.9900
14:92923403:AAG:A	donor_loss	0.9900
14:92923405:GGTG:G	donor_loss	0.9900
14:92923406:GTGA:G	donor_loss	0.9900
14:92923407:T:G	donor_loss	0.9900
14:92924197:A:AG	acceptor_gain	0.9900
14:92924198:G:GA	acceptor_gain	0.9900
14:92926675:A:T	donor_gain	0.9900
14:92926696:G:GT	donor_gain	0.9900
14:92927548:A:AG	acceptor_gain	0.9900
14:92927549:G:GG	acceptor_gain	0.9900
14:92927549:GAT:G	acceptor_gain	0.9900
14:92927617:AGG:A	donor_loss	0.9900
14:92927618:GG:G	donor_loss	0.9900
14:92927619:G:GG	donor_loss	0.9900
14:92927620:T:G	donor_loss	0.9900
14:92929710:A:AG	acceptor_gain	0.9900
14:92929711:T:G	acceptor_gain	0.9900
14:92929712:A:AG	acceptor_gain	0.9900
14:92929712:ACCAG:A	acceptor_gain	0.9900
14:92929713:C:G	acceptor_gain	0.9900
14:92929715:AG:A	acceptor_gain	0.9900

AlphaMissense

2992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:92926614:T:C	C35R	0.994
14:92927598:T:C	L79P	0.994
14:92926614:T:A	C35S	0.992
14:92926615:G:C	C35S	0.992
14:92927550:A:T	D63V	0.992
14:92926677:T:C	C56R	0.990
14:92927571:T:C	L70P	0.990
14:92934841:T:C	L444P	0.990
14:92926679:T:G	C56W	0.988
14:92927586:T:C	L75S	0.988
14:92926616:C:G	C35W	0.987
14:92926690:T:A	L60H	0.987
14:92927550:A:C	D63A	0.987
14:92926630:T:A	I40N	0.986
14:92926677:T:A	C56S	0.985
14:92926678:G:C	C56S	0.985
14:92926690:T:C	L60P	0.984
14:92932831:A:C	S424R	0.984
14:92932833:C:A	S424R	0.984
14:92932833:C:G	S424R	0.984
14:92926615:G:T	C35F	0.983
14:92926615:G:A	C35Y	0.982
14:92926630:T:G	I40S	0.981
14:92934829:T:A	I440N	0.981
14:92927559:T:C	I66T	0.980
14:92927607:T:C	L82P	0.980
14:92934834:G:C	A442P	0.980
14:92926618:T:A	I36N	0.979
14:92926621:T:A	V37D	0.979
14:92926678:G:A	C56Y	0.979

dbSNP variants (sampled 300 via entrez): RS1000019911 (14:92932744 A>G), RS1000032868 (14:92927693 A>G), RS1000051650 (14:92933303 G>A,T), RS1000144031 (14:92921404 A>C), RS1000428786 (14:92927301 G>A,C), RS1000590827 (14:92929171 G>A), RS1000597391 (14:92931966 C>A,T), RS1000657243 (14:92927890 G>A), RS1000697750 (14:92923287 A>C), RS1001323106 (14:92926995 G>T), RS1002281614 (14:92932021 C>G), RS1002947770 (14:92925962 G>A), RS1003099880 (14:92929554 C>G), RS1003374184 (14:92924686 C>A), RS1003402692 (14:92930848 A>G)

Disease associations

OMIM: gene MIM:118910 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005951_7	Body mass index	4.000000e-08
GCST006585_262	Blood protein levels	6.000000e-14
GCST006585_2672	Blood protein levels	1.000000e-07
GCST90000025_548	Appendicular lean mass	4.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Tunicamycin	decreases expression, increases expression	2
Thapsigargin	decreases expression, increases expression	2
securinine	decreases expression	1
testosterone enanthate	affects cotreatment, decreases expression	1
bisphenol A	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
cetrorelix	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	decreases expression	1
Lycopene	increases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Atrazine	decreases expression	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Camptothecin	increases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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