MED19

Summary

MED19 (mediator complex subunit 19, HGNC:29600) is a protein-coding gene on chromosome 11q12.1, encoding Mediator of RNA polymerase II transcription subunit 19 (A0JLT2). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. It is a selective cancer dependency (DepMap: 53.0% of cell lines).

The protein encoded by this gene is a subunit of the Mediator complex, which binds to gene-specific regulatory factors and provides support for the basal RNA polymerase II transcription machinery. This gene has been implicated in the growth of several types of cancer, and inhibition of its expression inhibits the growth and spread of these cancers. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 219541 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 2 total
• Cancer dependency (DepMap): dependent in 53.0% of screened cell lines
• MANE Select transcript: NM_001317078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29600
Approved symbol	MED19
Name	mediator complex subunit 19
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	LCMR1
Ensembl gene	ENSG00000156603
Ensembl biotype	protein_coding
OMIM	612385
Entrez	219541

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000337672, ENST00000431606, ENST00000528205, ENST00000534677, ENST00000645681, ENST00000917663, ENST00000917664

RefSeq mRNA: 2 — MANE Select: NM_001317078 NM_001317078, NM_153450

CCDS: CCDS7966, CCDS86203

Canonical transcript exons

ENST00000431606 — 5 exons

Exon	Start	End
ENSE00001027411	57704719	57704815
ENSE00001594061	57704302	57704396
ENSE00001698553	57703710	57704106
ENSE00003477697	57704973	57705229
ENSE00003846435	57711963	57712215

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 95.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3663 / max 114.9226, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119810	15.3379	1801
119811	2.0284	1316

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.77	gold quality
endothelial cell	CL:0000115	95.69	silver quality
secondary oocyte	CL:0000655	95.19	gold quality
pancreatic ductal cell	CL:0002079	94.52	gold quality
kidney epithelium	UBERON:0004819	93.92	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.46	gold quality
nipple	UBERON:0002030	91.28	gold quality
ileal mucosa	UBERON:0000331	90.32	gold quality
sural nerve	UBERON:0015488	89.91	gold quality
tibialis anterior	UBERON:0001385	89.72	gold quality
upper arm skin	UBERON:0004263	89.17	silver quality
corpus epididymis	UBERON:0004359	88.64	gold quality
left ventricle myocardium	UBERON:0006566	88.54	gold quality
lower lobe of lung	UBERON:0008949	88.32	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.26	gold quality
trachea	UBERON:0003126	88.21	gold quality
adult organism	UBERON:0007023	88.06	gold quality
pons	UBERON:0000988	87.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.90	gold quality
pericardium	UBERON:0002407	87.71	gold quality
pharyngeal mucosa	UBERON:0000355	87.70	gold quality
superior surface of tongue	UBERON:0007371	87.67	gold quality
skin of hip	UBERON:0001554	87.54	gold quality
cortical plate	UBERON:0005343	87.46	gold quality
ventral tegmental area	UBERON:0002691	87.32	gold quality
renal medulla	UBERON:0000362	87.16	gold quality
penis	UBERON:0000989	87.13	gold quality
pylorus	UBERON:0001166	87.06	gold quality
amniotic fluid	UBERON:0000173	86.98	gold quality
left testis	UBERON:0004533	86.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.03
E-CURD-112	no	2.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

60 targeting MED19, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-4291	99.20	68.88	2969

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 29)

• findings identify MED19/MED26 as a probable composite REST interface in Mediator and further clarify the mechanistic basis by which Mediator facilitates REST-imposed epigenetic restrictions on neuronal gene expression (PMID:19049968)
• upregulated expression of Med19 was found in breast cancer tissues; Med19 expression was significantly associated with tumor grade (PMID:20890603)
• LCMR1 was strongly overexpressed in NSCLC and its expression was significantly associated with clinical stage. (PMID:21306606)
• results provide new evidence of an important role for Med19 in the development of hepatocellular carcinomas (PMID:21372827)
• Med19 is markedly up-regulated in bladder cancer tissues (PMID:21478038)
• MED19 is a novel proliferation regulator that promotes growth of lung cancer cells (PMID:21519921)
• MED19 played an important role in cell growth and cell cycle progression of human osteosarcoma cells. (PMID:21542455)
• The effect of downregulation of LCMR1 by lentivirus-mediated small hairpin RNA (shRNA) on colorectal cancer cell proliferation and tumorigenesis was explored. (PMID:21732059)
• MED19 serves as a novel proliferation regulator that promotes growth of prostate cancer cells. (PMID:21871180)
• Med19 functions in promoting cellular growth and may be a useful therapeutic target in malignant gastric carcinoma (PMID:22565189)
• LCMR1 suppresses apoptosis in lung cancer cells and this effect is associated with multiple apoptosis-related proteins, including p53, Bax and Mcl-1. (PMID:23076562)
• High MED19 expression is associated with lung adenocarcinoma cell clone conformation, growth, and metastasis. (PMID:23098456)
• Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2. (PMID:23276457)
• High Med19 expression is associated with tongue cancer. (PMID:23705783)
• Data show that the expression of Mediator of RNA polymerase II transcription subunit 19 (Med19) was increased in Osteosarcoma (OS) samples from patients compared to normal bone tissues. (PMID:24565852)
• High expression of Med19 is associated with cisplatin resistance in non-small cell lung cancer cells. (PMID:25735376)
• LCMR1 modulation was sufficient to positively regulate endogenous Tspan8 expression, with concomitant in vitro phenotypic changes such as loss of melanoma cell-matrix adherence and increase in invasion, and Tspan8 expression promoted tumourigenicity in vivo. (PMID:27375018)
• Med19 promotes breast cancer cell proliferation and that this effect is associated with regulating CBFA2T3 and HEB expression. (PMID:27572702)
• FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of colorectal cancer (PMID:27811858)
• We knocked down the Med19 expression in prostate cancer cell lines LNCaP and PC3 by using lentivirus siRNA. Cell proliferation, anchor-independent growth, migration, and invasion were suppressed in Med19 knockdown prostate cancer cells. (PMID:28125713)
• The data suggest that Med19 expression correlates with aggressive characteristics of bladder cancer, and Med19 knockdown suppresses the proliferation and migration of cancer cells through down-regulating the Wnt/beta-catenin pathway. (PMID:28631286)
• DEK and LCMR1 were demonstrated to cooperate in the inhibition of apoptosis in lung cancer cells. (PMID:28765911)
• Med19 induces autophagy and enhances breast cancer cells resistance to the cytotoxic action of Adriamycin. Moreover, Med19 suppression inhibits autophagy and promotes chemosensitivity by targeting the HMGB1 signaling axis. (PMID:30161287)
• High MED19 expression is associated with breast cancer progression. (PMID:30583076)
• Med 19 inhibitioncouldreduce migration abilityof prostate cancer PC3 cells by epithelial-mesenchymal transition (PMID:31715665)
• MED19 alters AR occupancy and gene expression in prostate cancer cells, driving MAOA expression and growth under low androgen. (PMID:33513133)
• The role of mediator complex subunit 19 in human diseases. (PMID:34038190)
• Lung cancer metastasis-related protein 1 promotes the transferring from advanced metastatic prostate cancer to castration-resistant prostate cancer by activating the glucocorticoid receptor alpha signal pathway. (PMID:35184651)
• MED19 encodes two unique protein isoforms that confer prostate cancer growth under low androgen through distinct gene expression programs. (PMID:37880276)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	med19b	ENSDARG00000009472
danio_rerio	med19a	ENSDARG00000037392
mus_musculus	Med19	ENSMUSG00000027080
rattus_norvegicus	Med19	ENSRNOG00000006050
drosophila_melanogaster	MED19	FBGN0036761
caenorhabditis_elegans		WBGENE00007019

Protein

Protein identifiers

Mediator of RNA polymerase II transcription subunit 19 — A0JLT2 (reviewed: A0JLT2)

Alternative names: Lung cancer metastasis-related protein 1, Mediator complex subunit 19

All UniProt accessions (2): A0JLT2, J3KR33

UniProt curated annotations — full annotation on UniProt →

Function. Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.

Subunit / interactions. Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.

Subcellular location. Nucleus.

Similarity. Belongs to the Mediator complex subunit 19 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A0JLT2-1	1	yes
A0JLT2-2	2

RefSeq proteins (2): NP_001304007, NP_703151 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019403	Mediator_Med19_met	Family

Pfam: PF10278

UniProt features (19 total): helix 5, compositionally biased region 4, region of interest 2, splice variant 2, modified residue 2, chain 1, sequence conflict 1, strand 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7EMF	ELECTRON MICROSCOPY	3.5
8TRH	ELECTRON MICROSCOPY	3.7
7ENA	ELECTRON MICROSCOPY	4.07
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
7ENJ	ELECTRON MICROSCOPY	4.4
7NVR	ELECTRON MICROSCOPY	4.5
7LBM	ELECTRON MICROSCOPY	4.8
8GXQ	ELECTRON MICROSCOPY	5.04
8TQW	ELECTRON MICROSCOPY	8.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0JLT2-F1	65.46	0.06

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 (2): 194, 226

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9833110	RSV-host interactions
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-5663205	Infectious disease
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway
R-HSA-9824446	Viral Infection Pathways
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 110 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, TCF11_01, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_NUCLEAR_BODY, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_MEDIATOR_COMPLEX, GOBP_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION

GO Biological Process (5): positive regulation of transcription elongation by RNA polymerase II (GO:0032968), positive regulation of transcription by RNA polymerase II (GO:0045944), RNA polymerase II preinitiation complex assembly (GO:0051123), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (2): transcription coregulator activity (GO:0003712), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), mediator complex (GO:0016592), core mediator complex (GO:0070847)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Adipogenesis	1
Respiratory Syncytial Virus Infection Pathway	1
Metabolism of lipids	1
Metabolism	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
transcription initiation at RNA polymerase II promoter	2
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
transcription preinitiation complex assembly	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
core mediator complex	1
nuclear protein-containing complex	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MED19	MED10	Q9BTT4	987
MED19	MED18	Q9BUE0	977
MED19	MED31	Q9Y3C7	973
MED19	MED27	Q6P2C8	949
MED19	MED11	Q9P086	948
MED19	MED17	Q9NVC6	947
MED19	MED26	O95402	914
MED19	MED9	Q9NWA0	910
MED19	MED7	O43513	900
MED19	MED14	O60244	881
MED19	MED15	Q96RN5	873
MED19	MED13	Q9UHV7	871
MED19	MED22	Q15528	854
MED19	MED20	Q9H944	841
MED19	MED6	O75586	830

IntAct

100 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED10	MED19	psi-mi:“MI:0915”(physical association)	0.910
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
MED19	MED29	psi-mi:“MI:0915”(physical association)	0.890
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
MED18	MED19	psi-mi:“MI:0914”(association)	0.840

BioGRID (418): MED19 (Affinity Capture-MS), MED25 (Affinity Capture-MS), MED12 (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED1 (Affinity Capture-MS), MED27 (Affinity Capture-MS), MED31 (Affinity Capture-MS), MED26 (Affinity Capture-MS), POLR2A (Affinity Capture-MS), MED13L (Affinity Capture-MS), MED16 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED23 (Affinity Capture-MS), MED15 (Affinity Capture-MS)

ESM2 similar proteins: A0JLT2, A4QNZ7, A5PK23, B1AZP2, F5HSE3, O60293, O75420, O95402, P61129, P78312, P97839, Q03111, Q07FY3, Q08C81, Q08DM1, Q174D3, Q1LVC2, Q32NP7, Q3T044, Q4G0F8, Q5EAY2, Q5F368, Q5R8Q8, Q5U2R6, Q6DD45, Q6DRL8, Q6PEI3, Q7TN02, Q80Z38, Q8C1B1, Q8C1S0, Q8CFT2, Q8CGI1, Q8IVL1, Q8K4J6, Q90YL3, Q90YY5, Q969V6, Q96A73, Q99MR1

Diamond homologs: A0JLT2, Q07FY3, Q08C81, Q174D3, Q5EAY2, Q6DRL8, Q8C1S0, Q9N4F2, Q9VVL6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MED19	“form complex”	“Core mediator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 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
Respiratory Syncytial Virus Infection Pathway	23	105.3×	2e-41
RSV-host interactions	23	83.7×	5e-39
Adipogenesis	23	83.7×	5e-39
Regulation of lipid metabolism by PPARalpha	23	75.4×	6e-38
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	14	70.2×	6e-22
Transcriptional regulation of white adipocyte differentiation	23	69.4×	4e-37
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	14	64.1×	2e-21
PPARA activates gene expression	23	50.5×	1e-33

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	20	118.0×	4e-36
RNA polymerase II preinitiation complex assembly	21	111.9×	3e-37
positive regulation of transcription initiation by RNA polymerase II	21	111.9×	3e-37
transcription initiation at RNA polymerase II promoter	6	44.1×	2e-07
somatic stem cell population maintenance	9	43.7×	3e-11
transcription by RNA polymerase II	7	9.7×	3e-04
mRNA processing	6	9.3×	1e-03
protein ubiquitination	9	7.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

686 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57704299:TACCT:T	donor_loss	1.0000
11:57704301:C:A	donor_loss	1.0000
11:57704301:CCTT:C	donor_gain	1.0000
11:57704304:T:A	donor_gain	1.0000
11:57704328:T:TA	donor_gain	1.0000
11:57704397:C:CC	acceptor_gain	1.0000
11:57704713:TCTTA:T	donor_loss	1.0000
11:57704714:CTTA:C	donor_loss	1.0000
11:57704715:TTAC:T	donor_loss	1.0000
11:57704716:TACCT:T	donor_loss	1.0000
11:57704717:ACCTG:A	donor_loss	1.0000
11:57704718:C:CA	donor_loss	1.0000
11:57704813:CAA:C	acceptor_gain	1.0000
11:57704814:AACT:A	acceptor_loss	1.0000
11:57704815:ACTGA:A	acceptor_loss	1.0000
11:57704816:C:CC	acceptor_gain	1.0000
11:57704816:CT:C	acceptor_loss	1.0000
11:57704817:T:C	acceptor_loss	1.0000
11:57705105:C:A	donor_gain	1.0000
11:57705134:G:C	donor_gain	1.0000
11:57704102:CGATT:C	acceptor_gain	0.9900
11:57704105:TT:T	acceptor_gain	0.9900
11:57704107:C:CC	acceptor_gain	0.9900
11:57704107:CTGG:C	acceptor_loss	0.9900
11:57704271:A:AC	donor_gain	0.9900
11:57704272:C:CC	donor_gain	0.9900
11:57704394:TTT:T	acceptor_gain	0.9900
11:57704395:TTC:T	acceptor_loss	0.9900
11:57704396:TCTG:T	acceptor_loss	0.9900
11:57704398:T:C	acceptor_loss	0.9900

AlphaMissense

1613 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57704992:A:G	F152S	1.000
11:57705123:G:C	F108L	1.000
11:57705123:G:T	F108L	1.000
11:57705125:A:G	F108L	1.000
11:57704986:A:G	L154P	0.999
11:57704986:A:T	L154H	0.999
11:57704991:G:C	F152L	0.999
11:57704991:G:T	F152L	0.999
11:57704993:A:G	F152L	0.999
11:57705058:A:G	L130P	0.999
11:57705067:A:T	L127H	0.999
11:57705112:A:G	L112P	0.999
11:57705121:A:G	L109P	0.999
11:57705121:A:T	L109Q	0.999
11:57705124:A:G	F108S	0.999
11:57705133:A:T	L105Q	0.999
11:57705199:A:G	L83P	0.999
11:57705201:A:C	N82K	0.999
11:57705201:A:T	N82K	0.999
11:57704814:A:G	L159S	0.998
11:57705067:A:G	L127P	0.998
11:57705121:A:C	L109R	0.998
11:57705124:A:C	F108C	0.998
11:57705133:A:G	L105P	0.998
11:57705211:C:T	G79D	0.998
11:57705212:C:G	G79R	0.998
11:57704978:C:G	G157R	0.997
11:57704986:A:C	L154R	0.997
11:57705067:A:C	L127R	0.997
11:57705069:G:C	S126R	0.997

dbSNP variants (sampled 300 via entrez): RS1000327817 (11:57708535 C>G), RS1000407539 (11:57703919 G>C), RS1000435541 (11:57708159 G>A), RS1000655769 (11:57710668 G>A), RS1000662931 (11:57710091 G>A), RS1000777054 (11:57709765 T>C), RS1001792877 (11:57713371 C>T), RS1001921971 (11:57711856 A>G,T), RS1002049947 (11:57705448 G>A), RS1002078170 (11:57713576 A>G), RS1002081247 (11:57705664 A>C), RS1002228544 (11:57709336 G>A), RS1002540832 (11:57713668 C>A,T), RS1002614326 (11:57713903 G>A), RS1002676392 (11:57712502 C>A,T)

Disease associations

OMIM: gene MIM:612385 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002539_6	Schizophrenia	2.000000e-09
GCST004521_290	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004946_35	Schizophrenia	9.000000e-09
GCST005232_71	Neuroticism	7.000000e-11
GCST006803_71	Schizophrenia	1.000000e-09
GCST010796_593	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-10
GCST010796_594	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_595	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_596	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_597	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_598	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_599	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_600	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_601	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_602	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_603	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_604	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST90002405_281	Reticulocyte count	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004327	electrocardiography
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs576859	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs576859	MED19, TMX2	3	1.50	1	ethanol

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	2
FR900359	affects phosphorylation	1
chloroprocaine	decreases expression, decreases reaction	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Testosterone	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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