KRT20

Summary

KRT20 (keratin 20, HGNC:20412) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 20 (P35900). Plays a significant role in maintaining keratin filament organization in intestinal epithelia.

The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. This cytokeratin is a major cellular protein of mature enterocytes and goblet cells and is specifically expressed in the gastric and intestinal mucosa. The type I cytokeratin genes are clustered in a region of chromosome 17q12-q21.

Source: NCBI Gene 54474 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_019010

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20412
Approved symbol	KRT20
Name	keratin 20
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	CK20, K20, MGC35423
Ensembl gene	ENSG00000171431
Ensembl biotype	protein_coding
OMIM	608218
Entrez	54474

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000167588, ENST00000482529, ENST00000902423, ENST00000902424

RefSeq mRNA: 1 — MANE Select: NM_019010 NM_019010

CCDS: CCDS11379

Canonical transcript exons

ENST00000167588 — 8 exons

Exon	Start	End
ENSE00000395216	40882572	40882654
ENSE00000721314	40877380	40877417
ENSE00000721395	40879813	40879938
ENSE00000863440	40878145	40878365
ENSE00000863442	40880100	40880261
ENSE00000863443	40880614	40880770
ENSE00000863445	40884796	40885242
ENSE00001275723	40875889	40876458

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 99.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.6719 / max 1462.1010, expressed in 94 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165843	2.6719	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.69	gold quality
rectum	UBERON:0001052	99.53	gold quality
duodenum	UBERON:0002114	99.42	gold quality
vermiform appendix	UBERON:0001154	95.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.66	gold quality
small intestine	UBERON:0002108	93.44	gold quality
transverse colon	UBERON:0001157	92.49	gold quality
intestine	UBERON:0000160	83.38	gold quality
colon	UBERON:0001155	79.62	gold quality
colonic epithelium	UBERON:0000397	77.92	gold quality
mucosa of stomach	UBERON:0001199	75.85	gold quality
smooth muscle tissue	UBERON:0001135	74.22	gold quality
body of stomach	UBERON:0001161	70.71	gold quality
stomach	UBERON:0000945	69.53	gold quality
urinary bladder	UBERON:0001255	65.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	60.82	gold quality
fundus of stomach	UBERON:0001160	58.03	gold quality
gall bladder	UBERON:0002110	55.95	gold quality
right coronary artery	UBERON:0001625	54.11	gold quality
skin of abdomen	UBERON:0001416	49.51	gold quality
islet of Langerhans	UBERON:0000006	48.30	gold quality
muscle tissue	UBERON:0002385	47.61	gold quality
zone of skin	UBERON:0000014	47.49	gold quality
endocervix	UBERON:0000458	46.73	gold quality
skin of leg	UBERON:0001511	45.74	gold quality
lower esophagus mucosa	UBERON:0035834	45.37	silver quality
ectocervix	UBERON:0012249	45.34	gold quality
uterine cervix	UBERON:0000002	44.46	gold quality
pancreas	UBERON:0001264	44.06	gold quality
right uterine tube	UBERON:0001302	43.34	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	1748.52
E-MTAB-8410	yes	18.49
E-GEOD-125970	yes	16.26
E-ANND-3	yes	9.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHA15, CDX1, FOXC1

miRNA regulators (miRDB)

34 targeting KRT20, 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-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-496	98.66	69.80	931
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-8057	97.64	66.54	897

Literature-anchored findings (GeneRIF, showing 40)

• CK20 expression modified in H. pylori chronic gastritis (PMID:11642721)
• expression in lymph nodes correlates with poor prognosis in colorectal cancer (PMID:11844829)
• expression pattern is unique to Barrett’s esophagus (PMID:11857318)
• Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction (PMID:11962749)
• The detection of cancer metastasis in the lymph nodes in colon carcinoma is almost doubled (21.9% vs 11.1%) by CK-20 mRNA (PMID:12515621)
• CK 20 mRNA identification by RT-PCR is reliable and may be useful for early diagnosis in peritoneal dissemination of colon cancer (PMID:12636102)
• It is possible to apply a simple and reliable method for the detection of circulating tumor cells based on cytokeratin-20 and prostate stem cell antigen RT-PCR assays in gastrointestinal cancers. (PMID:12894563)
• Down regulation of cytokeratin 20 is associated with transitional and squamous cell carcinoma of the bladder (PMID:12954496)
• The combined expression of CK7 and CK20 has a low specificity in the distinction between esophageal and cardiac (stomach) adenocarcinomas. (PMID:14631371)
• Alteration of CK7 and CK20 expression profile that occurs early in small intestinal tumorigenesis. (PMID:15371952)
• Abnormal CK20 is a useful adjunct to morphology for confirming dysplasia. (PMID:15871722)
• Overexpressed in recurrent superficial urothelial carcinoma. (PMID:16286979)
• CK 20 expression defines a subtype of pancreas cancer with important biologic properties; when present, CK 20 expression is an early event in pancreatic carcinogenesis identifiable in precursor lesions (PMID:16362976)
• CK 20 mRNA expression in urine has the potential to identify patients at risk for recurrence. (PMID:16473461)
• K20 Ser(13) is a highly dynamic protein kinase C-related phosphorylation site that is induced during apoptosis and tissue injury (PMID:16608857)
• CK20 expression is significntly greater in mucinous cystdenomas than in intraductal papillary mucinous adenomas. (PMID:16722930)
• Dysregulation of CK20 expression is an early event in the carcinogenesis of papillary noninvasive bladder cancer. (PMID:17240035)
• Blood and bone marrow cells in colorectal cancer depleted of CD45 do not show an enrichment of cytokeratin 20 as shown by PCR. (PMID:17378731)
• CK20 is a sensitive and specific marker for Crooke’s cells in the anterior pituitary and cytoskeletal changes that occur in corticotrophs in response to hypercortisolism. (PMID:17525485)
• salivary gland neoplasms showed a CK7+/CK20- immunoprofile ranging from 5 to 100%; squamous carcinoma showed negative CK7/20 immunoexpression (PMID:17593078)
• Positive CK20 RT-PCR, depth of tumor invasion, lymph node status, metastasis and microvessel density are significantly correlated with vascular invasion. (PMID:18069772)
• Strong immunohistochemical expression of FGFR3, a superficial staining pattern of CK20, and a low proliferative activity define those papillary urothelial neoplasms of low malignant potential that do not recur. (PMID:18072261)
• Possible relationship between expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. (PMID:18092953)
• These results indicate that the epithelial barrier of the human adenoid is stably maintained by expression of tight junction proteins in the epithelium including Ck20-positive M-like cells. (PMID:18246436)
• tumor stage was related to cytokeratin 20 expression in the colorectal cancer patients (PMID:18265645)
• CK20-positive cells in lymph nodes and circulating mRNA in blood are detected in patients with colorectal neoplasms. (PMID:18387990)
• Loss of CDX2 and CK20 is more frequently encountered in mismatch repair-deficient colorectal cancer. (PMID:18587323)
• Micrometastases of gastric cancer can be detected in circulating peripheral blood using quantitative real-time RT-PCR. CK19 is a better marker than CK18, CK20 and CEA. (PMID:18705345)
• The diagnostic efficacy of urinary CD44 and cytokeratin 20 (CK20) mRNA in comparison with voided urine cytology (VUC) for the detection of bladder cancer, was evaluated. (PMID:18804101)
• GPC3 is frequently expressed in noncutaneous small cell neuroendocrine carcinoma of various origins, in particular in Merkel cell carcinoma, which, in combination with CK20 (PMID:18813128)
• CK20 and CEA are expressed in non-macroscopically involved lymph nodes of colorectal cancer. (PMID:19074466)
• It can be helpful in cases with metastatic rectal carcinoma, especially those with CK7+/CK20+ or CK20-/CK7- immunophenotype. (PMID:19098678)
• CK20 and MUC2 mRNA were quantitated in 52 normal lymph nodes from 12 patients undergoing surgery for benign bowel diseases and in 144 primary colon tumors. (PMID:19119477)
• The expression level of CK20 mRNA in the peripheral blood in patients with gastric cancer declines after postoperative adjuvant chemotherapy. (PMID:19145500)
• KRT20 is directly regulated by CDX1, suggesting a role for CDX1 in maintaining differentiation in intestinal epithelial cells (PMID:19188603)
• Data suggest that CD10 and CK20 may be used for the differential diagnosis of MCN and IPMN-BD. (PMID:19287335)
• CK20 and CEA are significantly more frequently detected in colon cancer patients than in healthy controls and can serve as markers. (PMID:19645077)
• CK20 expression is associated with the progression of breast cancer. (PMID:19664394)
• Chromogranin A, synaptophysin and CK 20 were not expressed in any basal cell carcinoma (PMID:19724850)
• MMP-11 and CK-20 are probable prognostic markers whose expression reflects the stages of tumor differentiation and LNM of breast cancer. (PMID:19914229)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt20	ENSMUSG00000035775
rattus_norvegicus	Krt20	ENSRNOG00000027139

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360)

Protein

Protein identifiers

Keratin, type I cytoskeletal 20 — P35900 (reviewed: P35900)

Alternative names: Cytokeratin-20, Keratin-20, Protein IT

All UniProt accessions (1): P35900

UniProt curated annotations — full annotation on UniProt →

Function. Plays a significant role in maintaining keratin filament organization in intestinal epithelia. When phosphorylated, plays a role in the secretion of mucin in the small intestine.

Subunit / interactions. Heterotetramer of two type I and two type II keratins. Associates with KRT8.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed predominantly in the intestinal epithelium. Expressed in luminal cells of colonic mucosa. Also expressed in the Merkel cells of keratinized oral mucosa; specifically at the tips of some rete ridges of the gingival mucosa, in the basal layer of the palatal mucosa and in the taste buds of lingual mucosa.

Post-translational modifications. Hyperphosphorylation at Ser-13 occurs during the early stages of apoptosis but becomes less prominent during the later stages. Phosphorylation at Ser-13 also increases in response to stress brought on by cell injury. Proteolytically cleaved by caspases during apoptosis. Cleavage occurs at Asp-228.

Miscellaneous. There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_061883* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (20 total): region of interest 7, sequence variant 3, mutagenesis site 3, sequence conflict 3, chain 1, domain 1, modified residue 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35900-F1	80.21	0.57

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 (1): 228–229 (cleavage; by caspases)

Post-translational modifications (1): 13

Mutagenesis-validated functional residues (3):

Position	Phenotype
13	promotes keratin filament disassembly.
14	no effect on keratin filament organization.
80	leads to collapsed filaments.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 128 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_SECRETION, STONER_ESOPHAGEAL_CARCINOGENESIS_UP, GOBP_CELLULAR_RESPONSE_TO_STARVATION, GOBP_REGULATION_OF_TRANSPORT, GOBP_TISSUE_MORPHOGENESIS, GATA_Q6, GOBP_RESPONSE_TO_STARVATION, LIU_CDX2_TARGETS_UP

GO Biological Process (6): morphogenesis of an epithelium (GO:0002009), apoptotic process (GO:0006915), cellular response to starvation (GO:0009267), epithelial cell differentiation (GO:0030855), intermediate filament organization (GO:0045109), regulation of protein secretion (GO:0050708)

GO Molecular Function (4): structural constituent of cytoskeleton (GO:0005200), structural constituent of skin epidermis (GO:0030280), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), intermediate filament (GO:0005882), keratin filament (GO:0045095), intermediate filament cytoskeleton (GO:0045111)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epithelium development	2
structural molecule activity	2
cytoskeleton	2
cellular anatomical structure	2
tissue morphogenesis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
cell differentiation	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
protein secretion	1
regulation of protein transport	1
regulation of secretion by cell	1
cytoskeleton organization	1
molecular_function	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
intermediate filament	1

Protein interactions and networks

STRING

1664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT20	CDX2	Q99626	909
KRT20	SYP	P08247	870
KRT20	CEACAM5	P06731	847
KRT20	NKX2-1	P43699	841
KRT20	PIP	P12273	840
KRT20	NAPSA	O96009	822
KRT20	PAX8	Q06710	797
KRT20	MUC2	Q02817	793
KRT20	CHGA	P10645	771
KRT20	UPK3A	O75631	728
KRT20	ENO2	P09104	727
KRT20	MME	P08473	724
KRT20	CALB2	P22676	721
KRT20	MUC5AC	P98088	718
KRT20	NCAM1	P13591	716
KRT20	MUC6	Q6W4X9	716

IntAct

165 interactions, top by confidence:

A	B	Type	Score
VIM	KRT20	psi-mi:“MI:0915”(physical association)	0.830
KRT20	VIM	psi-mi:“MI:0915”(physical association)	0.830
KRT20	BBLN	psi-mi:“MI:0915”(physical association)	0.810
BBLN	KRT20	psi-mi:“MI:0915”(physical association)	0.810
TFIP11	KRT20	psi-mi:“MI:0915”(physical association)	0.780
KRT20	TFIP11	psi-mi:“MI:0915”(physical association)	0.780
KRT20	KRT15	psi-mi:“MI:0915”(physical association)	0.740
NUP62	KRT20	psi-mi:“MI:0915”(physical association)	0.740
KRT15	KRT20	psi-mi:“MI:0915”(physical association)	0.740
KRT20	NUP62	psi-mi:“MI:0915”(physical association)	0.740
KRT20	TXLNA	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	KRT20	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (81): KRT20 (Two-hybrid), KRT20 (Two-hybrid), KRT20 (Two-hybrid), KRT20 (Two-hybrid), KRT20 (Two-hybrid), KRT20 (Two-hybrid), KRT20 (Two-hybrid), C9orf16 (Two-hybrid), USHBP1 (Two-hybrid), KRT40 (Two-hybrid), KRT80 (Two-hybrid), TXLNA (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid)

ESM2 similar proteins: A0A8C0N8E3, A6QQQ9, O62654, P02540, P02541, P02542, P02543, P02544, P03995, P05784, P08552, P08670, P09654, P14136, P17661, P20152, P23239, P23729, P24789, P24790, P25030, P31000, P31001, P31393, P35617, P35900, P47819, P48616, P48670, P48673, P48674, P48675, P48676, P48677, P84198, Q04948, Q28115, Q28706, Q4R4X4, Q58EE9

Diamond homologs: A1KQY9, A1L317, A1L595, A5A6M0, A5A6M5, A5A6N2, A5A6P3, A6BLY7, A6QQQ9, A7YWM2, B0LKP1, B1AQ75, O57607, O57611, O76009, O76013, O77727, O93256, P02533, P02534, P02535, P02537, P05781, P05783, P05784, P06394, P08727, P08728, P08730, P08777, P08778, P08779, P08802, P13645, P13646, P19001, P19012, P25030, P25690, P35527

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
p38	“up-regulates activity”	KRT20	phosphorylation
MAPKAPK2	“up-regulates activity”	KRT20	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the cornified envelope	12	28.5×	3e-13
Keratinization	18	27.1×	4e-20

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	15	95.0×	1e-24
morphogenesis of an epithelium	7	63.4×	2e-09
epithelial cell differentiation	8	37.0×	3e-09
keratinization	6	37.0×	7e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

698 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40877427:T:C	acceptor_gain	1.0000
17:40877428:T:TC	acceptor_gain	1.0000
17:40877430:T:C	acceptor_gain	1.0000
17:40877430:T:TC	acceptor_gain	1.0000
17:40877433:A:AC	acceptor_gain	1.0000
17:40877433:A:C	acceptor_gain	1.0000
17:40878143:A:AC	donor_gain	1.0000
17:40878144:C:CC	donor_gain	1.0000
17:40878144:CTTTA:C	donor_gain	1.0000
17:40878149:CGT:C	donor_gain	1.0000
17:40878187:T:A	donor_gain	1.0000
17:40879811:A:AC	donor_gain	1.0000
17:40879811:A:AG	donor_loss	1.0000
17:40879812:C:CC	donor_gain	1.0000
17:40879812:CCATG:C	donor_gain	1.0000
17:40879935:CAGT:C	acceptor_gain	1.0000
17:40879936:AGT:A	acceptor_gain	1.0000
17:40879937:GT:G	acceptor_gain	1.0000
17:40879938:TCTA:T	acceptor_loss	1.0000
17:40879939:C:CC	acceptor_gain	1.0000
17:40879939:CTA:C	acceptor_loss	1.0000
17:40879944:G:GC	acceptor_gain	1.0000
17:40879948:C:CT	acceptor_gain	1.0000
17:40879949:A:T	acceptor_gain	1.0000
17:40880099:CCTGT:C	donor_gain	1.0000
17:40880258:CTTC:C	acceptor_gain	1.0000
17:40880259:TTCC:T	acceptor_loss	1.0000
17:40880260:TCC:T	acceptor_loss	1.0000
17:40880261:CC:C	acceptor_loss	1.0000
17:40880262:C:CA	acceptor_loss	1.0000

AlphaMissense

2795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40884947:C:G	R80P	0.982
17:40878172:C:G	R371P	0.979
17:40878196:A:G	L363P	0.974
17:40878166:A:G	L373P	0.972
17:40880696:A:G	L183P	0.965
17:40880770:C:A	K158N	0.963
17:40880770:C:G	K158N	0.963
17:40884956:A:G	L77P	0.962
17:40878268:A:G	L339P	0.959
17:40880123:C:G	A257P	0.959
17:40878187:T:A	E366V	0.958
17:40882603:C:G	A148P	0.958
17:40884944:A:G	L81P	0.956
17:40880654:A:G	L197P	0.955
17:40884942:C:G	A82P	0.955
17:40878204:C:A	K360N	0.952
17:40878204:C:G	K360N	0.952
17:40882585:C:G	D154H	0.951
17:40880109:A:C	F261L	0.950
17:40880109:A:T	F261L	0.950
17:40880111:A:G	F261L	0.950
17:40884932:A:G	L85P	0.950
17:40880163:C:A	R243S	0.949
17:40880163:C:G	R243S	0.949
17:40884953:T:A	N78I	0.949
17:40879832:A:G	L300P	0.948
17:40880144:C:G	A250P	0.945
17:40880642:A:G	L201P	0.942
17:40878182:C:G	A368P	0.941
17:40882591:C:G	A152P	0.941

dbSNP variants (sampled 300 via entrez): RS1000096802 (17:40877903 A>G), RS1001038420 (17:40875824 G>A), RS1001089216 (17:40882438 C>G,T), RS1001421610 (17:40883679 T>C,G), RS1001594896 (17:40877545 A>G), RS1001717561 (17:40878642 G>A), RS1001804702 (17:40886345 C>G), RS1001879742 (17:40886754 G>T), RS1002320575 (17:40879012 G>A), RS1002457631 (17:40879975 G>C), RS1002499268 (17:40875400 G>A), RS1003034104 (17:40878661 C>T), RS1003471644 (17:40886175 C>T), RS1003850263 (17:40878611 G>A), RS1003894508 (17:40886031 T>G)

Disease associations

OMIM: gene MIM:608218 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000522_4	Height	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
methyleugenol	increases expression	1
methylselenic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	increases expression	1
Resveratrol	increases expression	1
Decitabine	affects cotreatment, increases expression	1
Arsenic	decreases expression	1
Estradiol	decreases expression, decreases reaction	1
Glucose	affects cotreatment, decreases expression, increases reaction	1
Hydrogen Peroxide	affects expression	1
N-Nitrosopyrrolidine	increases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety