CHRFAM7A

Summary

CHRFAM7A (CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion, HGNC:15781) is a protein-coding gene on chromosome 15q13.2, encoding CHRNA7-FAM7A fusion protein (Q494W8).

The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The family member CHRNA7, which is located on chromosome 15 in a region associated with several neuropsychiatric disorders, is partially duplicated and forms a hybrid with a novel gene from the family with sequence similarity 7 (FAM7A). Alternative splicing has been observed, and two variants exist, for this hybrid gene. The N-terminally truncated products predicted by the largest open reading frames for each variant would lack the majority of the neurotransmitter-gated ion-channel ligand binding domain but retain the transmembrane region that forms the ion channel. Although current evidence supports transcription of this hybrid gene, translation of the nicotinic acetylcholine receptor-like protein-encoding open reading frames has not been confirmed.

Source: NCBI Gene 89832 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_139320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15781
Approved symbol	CHRFAM7A
Name	CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion
Location	15q13.2
Locus type	gene with protein product
Status	Approved
Aliases	D-10, CHRNA7-DR1
Ensembl gene	ENSG00000166664
Ensembl biotype	protein_coding
OMIM	609756
Entrez	89832

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000299847, ENST00000397827, ENST00000401522, ENST00000562729, ENST00000567722, ENST00000569278, ENST00000570098, ENST00000692430, ENST00000853243

RefSeq mRNA: 2 — MANE Select: NM_139320 NM_139320, NM_148911

CCDS: CCDS32184, CCDS42008

Canonical transcript exons

ENST00000299847 — 10 exons

Exon	Start	End
ENSE00001231930	30386863	30386987
ENSE00001623005	30372147	30372341
ENSE00001704368	30371098	30371184
ENSE00001764950	30367418	30367527
ENSE00002578725	30393252	30393540
ENSE00002579504	30360566	30362811
ENSE00003471833	30377030	30377109
ENSE00003555124	30372978	30373145
ENSE00003561724	30383319	30383382
ENSE00003667438	30380353	30380399

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 83.83.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.42	gold quality
calcaneal tendon	UBERON:0003701	76.20	gold quality
descending thoracic aorta	UBERON:0002345	75.56	gold quality
monocyte	CL:0000576	75.24	gold quality
thoracic aorta	UBERON:0001515	74.44	gold quality
ascending aorta	UBERON:0001496	74.19	gold quality
bone marrow	UBERON:0002371	74.00	gold quality
leukocyte	CL:0000738	73.07	gold quality
right lung	UBERON:0002167	71.11	gold quality
thyroid gland	UBERON:0002046	70.86	gold quality
smooth muscle tissue	UBERON:0001135	70.53	gold quality
left lobe of thyroid gland	UBERON:0001120	70.27	gold quality
right lobe of thyroid gland	UBERON:0001119	70.26	gold quality
adrenal tissue	UBERON:0018303	70.11	gold quality
testis	UBERON:0000473	69.79	gold quality
right testis	UBERON:0004534	69.73	gold quality
left testis	UBERON:0004533	69.11	gold quality
vermiform appendix	UBERON:0001154	68.94	gold quality
tibial nerve	UBERON:0001323	68.48	gold quality
endocervix	UBERON:0000458	67.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.37	gold quality
mucosa of stomach	UBERON:0001199	67.24	gold quality
adipose tissue	UBERON:0001013	66.39	gold quality
endometrium	UBERON:0001295	65.99	gold quality
bone marrow cell	CL:0002092	65.91	gold quality
granulocyte	CL:0000094	65.85	gold quality
omental fat pad	UBERON:0010414	65.13	gold quality
tonsil	UBERON:0002372	65.04	gold quality
lymph node	UBERON:0000029	64.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	4.62
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting CHRFAM7A, 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-4692	100.00	67.32	2066
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1825	99.72	68.11	1089

Literature-anchored findings (GeneRIF, showing 40)

• 3-Mb map of 15q13-q14 showing that CHRFAM7A is part of a large segmental duplication in the opposite orientation to CHRNA7 and revealing several other duplications (PMID:11829490)
• Human mesothelioma cells and human biopsies of mesothelioma as well as of normal pleural mesothelial cells functionally express CHRNA7. (PMID:14729617)
• Results demonstrate that human and rat nicotinic acetylcholine receptors are senstive targets for volatile organic compounds in industrial products and are used in the risk assessment of these compounds. (PMID:15885267)
• CHRFAM7A was identified as a candidate gene in the D15S165 region in a study of allelic variants at chromosome 15q14 in schizophrenia. (PMID:16417613)
• These observations indicate that episodic memory function is a schizophrenia endophenotype and implicate the CHRFAM7A/CHRNA7 locus in modulating its function. (PMID:17012698)
• In persons with bipolar type schizoaffective disorder, CHRNA7 promoter region allelic variants are linked to the capacity to inhibit the P50 auditory evoked potential and thus are associated with a type of illness similar to schizophrenia. (PMID:17192894)
• In 20 smoking-matched people (n = 10 schizophrenia, n = 10 controls), we found significantly lower CHRFAM7A in cotinine and self-reported smokers versus nonsmokers (p (PMID:19082523)
• No significant associations of 2-bp deletion or CHRFAM7A copy number with antisaccade performance parameters were observed. (PMID:19149910)
• polymorphism of CHRFAM7A can be implicated in Alzheimer’s disease, dementia with Lewy bodies and Pick’s disease (PMID:19641318)
• the partially duplicated alpha7 nAChR subunit gene may specifically participate in the inflammatory response of the innate immune system. (PMID:20926142)
• evidence on the association between variations in CHRNA7 or CHRFAM7A and the risk of dementia is still sparse and inconclusive. Further studies are needed to establish whether some polymorphisms may affect the probability of developing dementia [review] (PMID:22300029)
• lack of CHRFAM7A expression in ADNFLE patients might be an important factor in the pathogenesis of autosomal dominant nocturnal frontal lobe epilepsy (PMID:23553139)
• the involvement of CHRFAM7A in the pathophysiology of the idiopathic generalized epilepsy and indication that c.497-498TG deletion or a nearby polymorphism in the CHRFAM7A gene may play a role in the pathogenesis of this disease (PMID:24024466)
• This association study was replicated in the NIA-LOAD Familial Study dataset. CHRFAM7A is a dominant negative regulator of CHRNA7 function, the receptor that facilitates amyloid-beta1-42 internalization through endocytosis and has been implicated in AD. (PMID:24787912)
• CHRFAM7A, a human-specific and partially duplicated alpha7-nicotinic acetylcholine receptor gene with the potential to specify a human-specific inflammatory response to injury. (PMID:25473097)
• Data show that a 1 kb sequence in the untranslated regions of the alpha7-nicotinic acetylcholine receptor (alpha7nAChR) gene CHRFAM7A that is modulated by lipopolysaccharides (LPS). (PMID:25681457)
• Data show preferential fetal CHRFAM7A expression in the human prefrontal cortex and suggest abnormalities in the CHRFAM7A/CHRNA7 ratios in schizophrenia and bipolar disorder, due mainly to overexpression of CHRFAM7A. (PMID:26206074)
• gp120IIIB promotes the downregulation of CHRFAM7A in neuronal cells. (PMID:26567012)
• Our study observations support the role for CHRFAM7A gene in schizophrenia pathogenesis and suggest a potential novel link between deficient CHRFAM7A expression and negative psychopathology (PMID:29305655)
• Genetic variation CHRFAM7A is associated with nicotine dependence and response to varenicline treatment. (PMID:30089821)
• Study suggests a negative modulatory effect of CHRFAM7A on synaptic transmission (relevance in schizophrenia) and a modulatory effect on Abeta1-42 uptake (relevance to Alzheimer disease). (PMID:30710073)
• Association of a Functional Polymorphism in the CHRFAM7A Gene with Inflammatory Response Mediators and Neuropathic Pain after Spinal Cord Injury. (PMID:30924722)
• The analysis of the CHRFAM7A gene’s regulatory region reveals some of the mechanisms driving its expression and responsiveness to LPS in human immune cell models. donepezil differently modulates CHRFAM7A responsiveness to LPS. (PMID:31048268)
• The CHRFAM7A gene contributes to the pathogenesis of neuropsychiatric disorders. (PMID:31348980)
• Acetylcholinesterase inhibitors targeting the cholinergic anti-inflammatory pathway: a new therapeutic perspective in aging-related disorders. (PMID:31583530)
• CHRFAM7A reduces monocyte/macrophage migration and colony formation in vitro. (PMID:32303780)
• Human-specific gene CHRFAM7A mediates M2 macrophage polarization via the Notch pathway to ameliorate hypertrophic scar formation. (PMID:32890966)
• CHRFAM7A Overexpression Attenuates Cerebral Ischemia-Reperfusion Injury via Inhibiting Microglia Pyroptosis Mediated by the NLRP3/Caspase-1 pathway. (PMID:33405023)
• The human-specific duplicated alpha7 gene inhibits the ancestral alpha7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release. (PMID:33515545)
• Effect of CHRFAM7A Delta2bp gene variant on secondary inflammation after spinal cord injury. (PMID:33956875)
• Structure, Dynamics, and Ligand Recognition of Human-Specific CHRFAM7A (Dupalpha7) Nicotinic Receptor Linked to Neuropsychiatric Disorders. (PMID:34067314)
• Regulation of the acetylcholine/alpha7nAChR anti-inflammatory pathway in COVID-19 patients. (PMID:34088975)
• The Human-Restricted Isoform of the alpha7 nAChR, CHRFAM7A: A Double-Edged Sword in Neurological and Inflammatory Disorders. (PMID:35408823)
• Up-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy. (PMID:36479618)
• Human-specific duplicate CHRFAM7A gene is associated with more severe osteoarthritis and amplifies pain behaviours. (PMID:36627169)
• Human-specific CHRFAM7A primes macrophages for a heightened pro-inflammatory response at the earlier stage of inflammation. (PMID:37655479)
• An original potentiating mechanism revealed by the cryo-EM structures of the human alpha7 nicotinic receptor in complex with nanobodies. (PMID:37749098)
• Structural mechanisms of alpha7 nicotinic receptor allosteric modulation and activation. (PMID:38382524)
• Unraveling the molecular interactions between alpha7 nicotinic receptor and a RIC3 variant associated with backward speech. (PMID:38472514)
• CHRFAM7A diversifies human immune adaption through Ca[2+] signalling and actin cytoskeleton reorganization. (PMID:38569318)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000101522
danio_rerio	chrna7a	ENSDARG00000101702
mus_musculus	Chrna7	ENSMUSG00000030525
rattus_norvegicus	Chrna7	ENSRNOG00000010853

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

CHRNA7-FAM7A fusion protein — Q494W8 (reviewed: Q494W8)

Alternative names: CHRNA7-DR1, D-10

All UniProt accessions (3): A0A0A6YYA8, Q494W8, H3BPP0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Expressed in hippocampus.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family.

RefSeq proteins (2): NP_647536, NP_683709 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

UniProt features (6 total): transmembrane region 5, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q494W8-F1	69.27	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_COGNITION, chr15q13, GOBP_CELL_CELL_SIGNALING, AGTCTTA_MIR499, CATRRAGC_UNKNOWN, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_SYNAPTIC_SIGNALING, GOCC_NEURON_PROJECTION, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE, GOCC_TRANSPORTER_COMPLEX

GO Biological Process (9): chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), cognition (GO:0050890), monoatomic ion transport (GO:0006811), negative regulation of monoatomic ion transmembrane transport (GO:0034766), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079), negative regulation of excitatory postsynaptic potential (GO:0090394)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), ion channel inhibitor activity (GO:0008200)

GO Cellular Component (6): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transmembrane transport	2
anterograde trans-synaptic signaling	1
monoatomic ion transport	1
transmembrane transport	1
regulation of biological quality	1
nervous system process	1
transport	1
negative regulation of transmembrane transport	1
regulation of monoatomic ion transmembrane transport	1
negative regulation of monoatomic ion transport	1
regulation of membrane potential	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
negative regulation of biological process	1
excitatory postsynaptic potential	1
modulation of excitatory postsynaptic potential	1
signaling receptor activity	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
postsynaptic neurotransmitter receptor activity	1
ligand-gated monoatomic cation channel activity	1
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
monoatomic ion channel activity	1
channel inhibitor activity	1
transmembrane transporter binding	1
ion channel regulator activity	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
plasma membrane signaling receptor complex	1
plasma membrane bounded cell projection	1
cell junction	1
synaptic membrane	1
postsynapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRFAM7A	OTUD7A	Q8TE49	962
CHRFAM7A	ARHGAP11B	Q3KRB8	582
CHRFAM7A	SLC35F2	Q8IXU6	574
CHRFAM7A	HNRNPCL1	O60812	570
CHRFAM7A	ULK4	Q96C45	564
CHRFAM7A	MTMR10	Q9NXD2	544
CHRFAM7A	DOP1B	Q9Y3R5	510
CHRFAM7A	IMMP2L	Q96T52	476
CHRFAM7A	RIC3	Q7Z5B4	475
CHRFAM7A	TRPM1	Q7Z4N2	431
CHRFAM7A	CSMD1	Q96PZ7	402
CHRFAM7A	FAN1	Q9Y2M0	394
CHRFAM7A	CAPN1	P07384	392
CHRFAM7A	GOLGA8H	P0CJ92	359
CHRFAM7A	BCHE	P06276	357

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CHRFAM7A	CHRNA7	psi-mi:“MI:0915”(physical association)	0.400
CHRNA7	CHRFAM7A	psi-mi:“MI:0915”(physical association)	0.400
CHRFAM7A	CFTR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): CHRFAM7A (Negative Genetic), CHRFAM7A (PCA), CHRFAM7A (Affinity Capture-RNA)

ESM2 similar proteins: A8MPY1, F1R8P4, O75311, O93430, P02713, P02714, P02715, P02716, P02717, P02718, P04759, P05376, P09628, P09660, P09690, P20782, P22770, P22771, P23415, P23416, P24046, P24524, P25110, P26714, P28476, P43144, P47742, P49580, P49582, P50572, P50573, P54244, P56475, P56476, P57695, Q05941, Q07001, Q08832, Q0II76, Q24352

Diamond homologs: A5X5Y0, O70212, O95264, P04757, P05376, P18845, P19370, P22770, P23979, P26153, P32297, P35563, P36544, P43143, P43679, P46098, P48182, P49581, P49582, P54131, Q05941, Q07263, Q15825, Q494W8, Q5IS76, Q68RJ7, Q70Z44, Q866A2, Q8R4G9, Q8WXA8, Q9I8C7, Q9JHJ5, Q9JJ16, A8WQK3, O16926, O70174, P02708, P02709, P02710, P02711

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	43
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
147433	GRCh38/hg38 15q13.2-13.3(chr15:30361674-32569425)x1	Pathogenic
148179	GRCh38/hg38 15q13.2-13.3(chr15:30361674-32414682)x3	Pathogenic
564147	GRCh37/hg19 15q11.2-13.2(chr15:22770421-31073668)x3,4	Pathogenic
564148	GRCh37/hg19 15q11.2-13.3(chr15:22770421-32421780)x2,3	Pathogenic
58653	GRCh38/hg38 15q13.2-13.3(chr15:30361674-31317476)x1	Pathogenic
929340	GRCh37/hg19 15q13.1-13.3(chr15:28962131-32620127)x1	Pathogenic
545175	NC_000015.10:g.(?28821222)(30470957_?)del	Likely pathogenic

SpliceAI

1947 predictions. Top by Δscore:

Variant	Effect	Δscore
15:30367417:CCCA:C	donor_gain	1.0000
15:30367420:A:AC	donor_gain	1.0000
15:30367421:C:CC	donor_gain	1.0000
15:30367528:C:CC	acceptor_gain	1.0000
15:30372342:C:T	acceptor_gain	1.0000
15:30372344:CCA:C	acceptor_gain	1.0000
15:30372345:C:T	acceptor_gain	1.0000
15:30372345:CA:C	acceptor_gain	1.0000
15:30372346:A:AC	acceptor_gain	1.0000
15:30372346:A:C	acceptor_gain	1.0000
15:30372346:A:T	acceptor_gain	1.0000
15:30377024:GCTTA:G	donor_loss	1.0000
15:30377025:CTTAC:C	donor_loss	1.0000
15:30377026:TTA:T	donor_loss	1.0000
15:30377027:TA:T	donor_loss	1.0000
15:30377028:ACCT:A	donor_loss	1.0000
15:30377029:C:CG	donor_loss	1.0000
15:30377105:CAGCA:C	acceptor_gain	1.0000
15:30377107:GCACT:G	acceptor_loss	1.0000
15:30377108:CA:C	acceptor_gain	1.0000
15:30377108:CACTA:C	acceptor_loss	1.0000
15:30377109:ACT:A	acceptor_loss	1.0000
15:30377110:C:CC	acceptor_gain	1.0000
15:30377111:T:C	acceptor_loss	1.0000
15:30380344:GTTAC:G	donor_loss	1.0000
15:30380345:TTACT:T	donor_loss	1.0000
15:30380346:TACTT:T	donor_loss	1.0000
15:30380347:ACT:A	donor_loss	1.0000
15:30380348:CT:C	donor_loss	1.0000
15:30380349:TTACA:T	donor_loss	1.0000

AlphaMissense

2723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:30362396:C:G	R379P	1.000
15:30362399:T:A	D378V	1.000
15:30362411:G:T	A374D	1.000
15:30367464:A:G	L225P	1.000
15:30371153:G:C	F185L	1.000
15:30371153:G:T	F185L	1.000
15:30371155:A:G	F185L	1.000
15:30372184:G:C	F162L	1.000
15:30372184:G:T	F162L	1.000
15:30372186:A:G	F162L	1.000
15:30362377:G:C	F385L	0.999
15:30362377:G:T	F385L	0.999
15:30362379:A:G	F385L	0.999
15:30362387:A:G	L382P	0.999
15:30362391:A:G	C381R	0.999
15:30362393:A:G	L380P	0.999
15:30362399:T:G	D378A	0.999
15:30362400:C:G	D378H	0.999
15:30362412:C:G	A374P	0.999
15:30362414:G:T	A373D	0.999
15:30362422:C:A	W370C	0.999
15:30362422:C:G	W370C	0.999
15:30362424:A:G	W370R	0.999
15:30362424:A:T	W370R	0.999
15:30367494:C:T	G215D	0.999
15:30367495:C:G	G215R	0.999
15:30371148:A:G	L187P	0.999
15:30371163:A:G	L182P	0.999
15:30371169:A:G	L180P	0.999
15:30371169:A:T	L180H	0.999

dbSNP variants (sampled 300 via entrez): RS1000848377 (15:30377792 G>A), RS1001088302 (15:30377195 CA>C), RS1002165289 (15:30374552 A>G,T), RS1003305657 (15:30371794 C>G,T), RS1003388350 (15:30367931 G>C), RS1003589034 (15:30371288 G>A), RS1005015541 (15:30387356 G>A), RS1005089123 (15:30382406 T>G), RS1005717207 (15:30371739 G>A), RS1006023147 (15:30375166 G>C), RS1006095179 (15:30374546 C>T), RS1006869568 (15:30369349 G>T), RS1007108462 (15:30368865 A>G), RS1007203648 (15:30373657 T>C), RS1007444109 (15:30372619 T>G)

Disease associations

OMIM: gene MIM:609756 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance	2
Particulate Matter	increases expression, decreases expression, affects cotreatment, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
trichostatin A	increases expression	1
dinophysistoxin 1	increases expression	1
bisphenol S	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Allergens	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	decreases 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