CALHM1

Summary

CALHM1 (calcium homeostasis modulator 1, HGNC:23494) is a protein-coding gene on chromosome 10q24.33, encoding Calcium homeostasis modulator protein 1 (Q8IU99). Pore-forming subunit of gustatory voltage-gated ion channels required for sensory perception of sweet, bitter and umami tastes.

This gene encodes a calcium channel that plays a role in processing of amyloid-beta precursor protein. A polymorphism at this locus has been reported to be associated with susceptibility to late-onset Alzheimer’s disease in some populations, but the pathogenicity of this polymorphism is unclear.

Source: NCBI Gene 255022 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 73 total — 1 likely-pathogenic
• MANE Select transcript: NM_001001412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23494
Approved symbol	CALHM1
Name	calcium homeostasis modulator 1
Location	10q24.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185933
Ensembl biotype	protein_coding
OMIM	612234
Entrez	255022

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329905

RefSeq mRNA: 1 — MANE Select: NM_001001412 NM_001001412

CCDS: CCDS7550

Canonical transcript exons

ENST00000329905 — 2 exons

Exon	Start	End
ENSE00001297659	103453240	103455747
ENSE00001303973	103458197	103458900

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 67.26.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	67.26	silver quality
epithelium of nasopharynx	UBERON:0001951	67.24	gold quality
nipple	UBERON:0002030	67.07	gold quality
prefrontal cortex	UBERON:0000451	67.05	gold quality
layer of synovial tissue	UBERON:0007616	66.46	silver quality
saphenous vein	UBERON:0007318	66.32	gold quality
pericardium	UBERON:0002407	66.14	silver quality
vena cava	UBERON:0004087	66.08	gold quality
superior surface of tongue	UBERON:0007371	65.93	gold quality
pons	UBERON:0000988	65.92	gold quality
substantia nigra pars reticulata	UBERON:0001966	65.79	gold quality
lateral globus pallidus	UBERON:0002476	65.79	silver quality
tongue	UBERON:0001723	65.77	gold quality
body of tongue	UBERON:0011876	65.77	gold quality
dorsal root ganglion	UBERON:0000044	65.74	gold quality
cerebellar vermis	UBERON:0004720	65.70	gold quality
pylorus	UBERON:0001166	65.69	gold quality
substantia nigra pars compacta	UBERON:0001965	65.69	silver quality
trachea	UBERON:0003126	65.63	gold quality
lateral nuclear group of thalamus	UBERON:0002736	65.43	gold quality
superior vestibular nucleus	UBERON:0007227	65.38	silver quality
renal medulla	UBERON:0000362	65.30	gold quality
penis	UBERON:0000989	64.97	gold quality
pharyngeal mucosa	UBERON:0000355	64.94	gold quality
frontal cortex	UBERON:0001870	63.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	63.51	gold quality
right frontal lobe	UBERON:0002810	62.12	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	61.71	gold quality
neocortex	UBERON:0001950	61.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting CALHM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-133A-5P	99.28	69.13	941

Literature-anchored findings (GeneRIF, showing 34)

• Study determined that the CALHM1 P86L polymorphism is associated with Alzheimer’s disease, further found that the P86L polymorphism increases amyloid-beta levels by interfering with CALHM1-mediated Ca(2+) permeability. (PMID:18585350)
• [Review] Expression of CALHM1 is found in all brain regions and cells of neuronal lineage; it localizes predominantly to the endoplasmic reticulum but also exists at the plasma membrane, where it forms a novel calcium influx route to the cytosol. (PMID:18667147)
• Protein may be a genetic determinant of Alzheimer disease, since a polymorphism reduces calcium permeability. (PMID:19038093)
• Study assessed the potential association between Alzheimer’s Disease risk and the Pro86Leu variant in the CALHM1 gene; no association was observed, either in the individual samples or in the combined analyses of more than 8100 subjects (PMID:19070563)
• No association with risk of late-onset Alzheimer disease (p=0.368 for genotypes; p=0.796 for alleles) was observed in the study, however, a potential modest association of minor allele homozygosity (TT) with an earlier age-at-onset was seen. (PMID:19191331)
• Study suggests the polymorphism does not contribute significantly to Alzheimer dementia risk in the Belgian population. (PMID:19191332)
• CALHM1 polymorphism is not associated with late-onset Alzheimer disease. (PMID:19472444)
• This study demonistrated that CALHM1 allele (13.5% vs 16.7%) and genotype frequency was not significantly different between Alzheimer’s disease (AD) and controls. (PMID:19545933)
• the CALHM1 P86L common variant may not influence Alzheimer disease risk in Japanese (PMID:19655363)
• Cells carrying the P86L mutation of CALHM1 channel may have mitochondria more vulnerable to Ca2+ overload and to apoptotic stimuli. (PMID:19944073)
• we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated Alzheimer’s disease biomarkers A beta 42, tau and phospho-tau (PMID:20005921)
• The CALHM1-P86L polymorphism is associated with Alzheimer’s disease in the ethnic Chinese Han population. (PMID:20061624)
• This study failed to show an association between theeight SNPs of the CALHM1 genes and alzheimer disease. (PMID:20164573)
• The present study might help to highlight the CALMH1gene as an excellent candidate for AD genetic susceptibility. (PMID:20164592)
• The results of this study did not confirm an association between the CALHM1 variation and AD, thus suggesting a genetic heterogeneity among the various populations. (PMID:20164602)
• This study for the first time finds that the GOLPH2 modifies the ApoE[varepsilon]4-associated risk of Alzheimer’s disease. (PMID:20592574)
• These results indicate that the CALHM1 Pro86Leu polymorphism may modulate age of onset of Alzheimer’s disease by interacting with the effect of the epsilon4 allele of apolipoprotein E. (PMID:20847397)
• An association between the CALHM1 polymorphism and the risk for Alzheimer’s disease, was not detected. (PMID:21378601)
• The results of this study provide the first evidence that the SNP rs11191692 in CALHM1 confers highly increased susceptibility to temporal lobe epilepsy. (PMID:21439911)
• CALHM1 increases Ca(2+) leak from the ER and, more importantly, reduces the endoplasmic reticulum Ca(2+) uptake by decreasing both the transport capacity and the Ca(2+) affinity of SERCA. (PMID:21574960)
• Data show a significant association of CALHM1 P86L with elevated CSF Abeta42 and Abeta40 in the normal cohort at risk for Alzheimer’s disease. (PMID:21629967)
• A TGG haplotype defined by the rs4918016-rs2986017-rs2986018 block was associated with sporadic Creutzfeldt-Jakob disease. (PMID:22874670)
• Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins. (PMID:23300080)
• The study identifies a previously uncharacterized mechanism of control of Ca(2+)-dependent ERK1/2 signaling in neurons, and further establishes CALHM1 as a critical ion channel for neuronal signaling and function. (PMID:23345406)
• CALHM1 is a voltage-gated ATP-release channel required for sweet, bitter and umami taste perception (PMID:23467090)
• Our data show that CLHM-1 is a functionally conserved ion channel that plays an important but potentially toxic role in excitable cell function. (PMID:23884934)
• rare genetic variants in CALHM1 lead to Ca(2+) dysregulation and may contribute to the risk of EOAD through a mechanism independent from the classical Ass cascade. (PMID:24069280)
• This study showed that No association between polymorphisms in the calcium homeostasis modulator 1 gene and mesial temporal lobe epilepsy risk in a Chinese population (PMID:24326043)
• CALHM1 p.P86L variation may not be an AD susceptibility factor in the Han Chinese population. (PMID:24630757)
• The rare R154H variant interferes with CALHM1 control of cytosolic Ca2+ and Abeta accumulation. (PMID:25386646)
• In the presence of antibody, P86L-CALHM1 shifts the balance between neurodegeneration and neuronal survival toward the stimulation of pro-cytotoxic pathways, thus potentially contributing to its deleterious effects in Alzheimer’s disease. (PMID:26416646)
• Meta-analysis suggested that CALHM1 rs2986017 might be associated with increased Alzheimer’s disease risk in Caucasian, but not Asian population (PMID:26700797)
• CALHM1 polymorphism may be potential biomarker in patients with Alzheimer disease. [meta-analysis] (PMID:26944452)
• Thermosensitivity of the voltage-dependent activation of calcium homeostasis modulator 1 (calhm1) ion channel. (PMID:33199024)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	calhm1b	ENSDARG00000005314
danio_rerio	calhm1a	ENSDARG00000077021
mus_musculus	Calhm1	ENSMUSG00000079258
rattus_norvegicus	Calhm1	ENSRNOG00000030682
caenorhabditis_elegans		WBGENE00016626

Paralogs (5): CALHM2 (ENSG00000138172), CALHM4 (ENSG00000164451), CALHM5 (ENSG00000178033), CALHM3 (ENSG00000183128), CALHM6 (ENSG00000188820)

Protein

Protein identifiers

Calcium homeostasis modulator protein 1 — Q8IU99 (reviewed: Q8IU99)

Alternative names: Protein FAM26C

All UniProt accessions (1): Q8IU99

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of gustatory voltage-gated ion channels required for sensory perception of sweet, bitter and umami tastes. With CALHM3 forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways. Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to membrane depolarization and low extracellular Ca(2+) concentration. Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of small ions including Ca(2+), Na(+), K(+) and Cl(-), as well as larger ions such as ATP(4-). Mediates Ca(2+) influx and downstream activation of the ERK1 and ERK2 cascade in neurons. Triggers endoplasmic reticulum stress by reducing the Ca(2+) content of the endoplasmic reticulum. May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+)-dependent manner.

Subunit / interactions. Oligomerizes to form hexamers and octamers. Does not form gap junctions. Associates with CALHM3 as a pore-forming subunit in a hetero-hexameric channel complex.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Basolateral cell membrane.

Tissue specificity. Predominantly expressed in adult brain. Detected also in retinoic acid-differentiated SH-SY5Y cells. Specifically expressed in circumvallate taste bud cells.

Post-translational modifications. N-glycosylated. Assembly with CALHM3 is associated with N-glycan remodeling and formation of hybrid complex- and high mannose-type glycochains. This N-glycan processing regulates channel trafficking and gating kinetics. Palmitoylated by ZDHHC3, ZDHHC20 and possibly ZDHHC7. Palmitoylation regulates voltage-dependent gating of the channel by shifting it toward more depolarized potentials.

Activity regulation. Regulated by membrane voltage and extracellular Ca(2+). Inhibited by Gd(3+), ruthenium red, and Zn(2+) and partially inhibited by 2-aminoethoxydiphenyl borate.

Domain organisation. A phospholipid-binding pocket is formed between conserved regions of S3 and S4 helices of one subunit and S2 of the adjacent subunit. It may regulate channel assembly and gating.

Polymorphism. Leu-86 causes a dysregulation of Ca(2+) homeostasis and amyloid precursor protein (APP) metabolism and has been suggested to be a risk factor for the development of Alzheimer disease. However, this association with Alzheimer disease could not be confirmed in a number of studies performed in different populations. According to a meta-analysis study, Leu-86 is likely not a genetic determinant of Alzheimer disease but may modulate age of onset by interacting with the effect of the APOE*4 allele of the APOE gene.

Similarity. Belongs to the CALHM family.

RefSeq proteins (1): NP_001001412* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029569	CALHM	Family

Pfam: PF14798

Catalyzed reactions (Rhea), 9 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• chloride(in) = chloride(out) (RHEA:29823)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• ATP(in) = ATP(out) (RHEA:75687)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (61 total): mutagenesis site 18, helix 11, turn 8, topological domain 5, region of interest 5, transmembrane region 4, lipid moiety-binding region 2, disulfide bond 2, chain 1, site 1, glycosylation site 1, sequence variant 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8GMP	ELECTRON MICROSCOPY	2.8
8GMR	ELECTRON MICROSCOPY	3.76
8S8Z	ELECTRON MICROSCOPY	3.91
8S90	ELECTRON MICROSCOPY	4.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IU99-F1	75.25	0.26

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): 74 (not glycosylated)

Post-translational modifications (2): 101, 208

Disulfide bonds (2): 42–127, 44–161

Glycosylation sites (1): 140

Mutagenesis-validated functional residues (18):

Position	Phenotype
10	decreases channel conductance. decreases the inhibition of channel activity by ruthenium red.
13	decreases channel conductance. decreases the inhibition of channel activity by ruthenium red.
16	markedly decreases channel conductance and confers resistance to inhibition by ruthenium red.
67	decreases channel expression at the plasma membrane.
72	significant inhibition on the control of cytosolic ca(2+) levels. does not affect ion channel activity.
74	has no effect on glycosylation.
109	results in approximately five-fold increase in channel current density. does not affect channel expression at the plasma
112	decreases channel expression at the plasma membrane. does not affect channel conductance.
114	impairs the ability to activate the erk1 and erk2 cascade.
116	decreases channel expression at the plasma membrane. does not affect channel conductance.
121	impaired ion channel activity in response to change in extracellular ca(2+) concentration.
121	no effect.
140	prevents glycosylation and impairs ability to activate the erk1 and erk2 cascade.
163	no effect.
166	no effect.
192	impairs channel expression at the plasma membrane.
196	decreases channel expression at the plasma membrane. does not affect channel conductance.
199	increases channel expression at the plasma membrane. does not affect channel conductance.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste
R-HSA-9730628	Sensory perception of salty taste
R-HSA-9709957	Sensory Perception
R-HSA-9717189	Sensory perception of taste

MSigDB gene sets: 79 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, TGACCTY_ERR1_Q2, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_SENSORY_PERCEPTION_OF_TASTE, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, HNF4_01, GOBP_PURINE_NUCLEOTIDE_TRANSPORT, GOBP_SENSORY_PERCEPTION, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_REGULATION_OF_TRANSPORT, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT

GO Biological Process (14): monoatomic cation transport (GO:0006812), ATP transport (GO:0015867), regulation of monoatomic ion transmembrane transport (GO:0034765), sensory perception of bitter taste (GO:0050913), sensory perception of sweet taste (GO:0050916), sensory perception of umami taste (GO:0050917), protein homooligomerization (GO:0051260), protein heterooligomerization (GO:0051291), ATP export (GO:1904669), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), sensory perception of taste (GO:0050909), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (8): calcium-activated cation channel activity (GO:0005227), voltage-gated monoatomic ion channel activity (GO:0005244), voltage-gated calcium channel activity (GO:0005245), monoatomic cation channel activity (GO:0005261), identical protein binding (GO:0042802), calcium channel activity (GO:0005262), protein binding (GO:0005515), voltage-gated channel activity (GO:0022832)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), plasma membrane raft (GO:0044853), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sensory perception of taste	2
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of taste	3
monoatomic ion transport	2
protein complex oligomerization	2
monoatomic ion channel activity	2
plasma membrane region	2
purine ribonucleotide transport	1
adenine nucleotide transport	1
monoatomic ion transmembrane transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
ATP transport	1
transport	1
metal ion transport	1
transmembrane transport	1
sensory perception of chemical stimulus	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
voltage-gated channel activity	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic cation transmembrane transporter activity	1
protein binding	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
binding	1
gated channel activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane	1
membrane raft	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALHM1	TRPM5	Q9NZQ8	796
CALHM1	CTNNA3	Q9UI47	755
CALHM1	PLCB2	Q00722	731
CALHM1	PANX1	Q96RD7	728
CALHM1	TAS1R2	Q8TE23	691
CALHM1	APP	P05067	681
CALHM1	OTOP1	Q7RTM1	609
CALHM1	P2RX2	Q9UBL9	603
CALHM1	TAS1R1	Q7RTX1	595
CALHM1	TAS1R3	Q7RTX0	594
CALHM1	PSEN1	P49768	584
CALHM1	GNAT3	A8MTJ3	582
CALHM1	APOE	P02649	558
CALHM1	TRPM4	Q8TD43	540
CALHM1	PKD2L1	Q9P0L9	540

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CALHM1	CSNK1D	psi-mi:“MI:0915”(physical association)	0.560
APP	CALHM1	psi-mi:“MI:0915”(physical association)	0.560
CALHM1	CALHM1	psi-mi:“MI:0915”(physical association)	0.520
DICER1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): CALHM1 (Proximity Label-MS)

ESM2 similar proteins: A1L134, A4D1U4, A6NFY4, A7MB75, D3Z291, F1NNL1, O43292, O95870, P51571, P70295, Q0PGW2, Q0VF94, Q17RQ9, Q1JPD2, Q28DH9, Q2HJ63, Q2TBX5, Q3U128, Q3U284, Q3UHG7, Q3UX43, Q4R8P0, Q5FVM1, Q5HYA8, Q5NDE9, Q5NDF0, Q5NDF2, Q5R6S0, Q5RBT8, Q5REH6, Q5RJQ8, Q6DDX8, Q6MG55, Q8BJQ9, Q8BXQ2, Q8C1F4, Q8IU99, Q8J025, Q8TDX6, Q8VEC4

Diamond homologs: D3Z291, H2MCM1, J3QMI4, Q5R3K3, Q5RJQ8, Q86XJ0, Q8IU99, Q8VEC4, Q9HA72, Q2HJ63, A4FUN9, Q561R8, Q5FWS4, Q5JW98, Q8C9E8, Q8CE93, Q8N5C1, Q8R100

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	71
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
381737	NM_001001412.4(CALHM1):c.461G>A (p.Arg154His)	Likely pathogenic

SpliceAI

253 predictions. Top by Δscore:

Variant	Effect	Δscore
10:103455745:CGC:C	acceptor_gain	1.0000
10:103455745:CGCCT:C	acceptor_loss	1.0000
10:103455746:GCC:G	acceptor_loss	1.0000
10:103455748:C:CC	acceptor_gain	1.0000
10:103455748:CTGTG:C	acceptor_loss	1.0000
10:103455749:T:G	acceptor_loss	1.0000
10:103455743:AGCGC:A	acceptor_gain	0.9900
10:103455744:GCGC:G	acceptor_gain	0.9900
10:103455745:CGCC:C	acceptor_gain	0.9900
10:103455746:GC:G	acceptor_gain	0.9900
10:103455747:CC:C	acceptor_gain	0.9900
10:103455750:G:GC	acceptor_gain	0.9700
10:103458193:TCA:T	donor_loss	0.9700
10:103458194:CAC:C	donor_loss	0.9700
10:103458195:A:AT	donor_loss	0.9700
10:103458196:C:CG	donor_loss	0.9700
10:103455750:G:C	acceptor_gain	0.9600
10:103458223:CGG:C	donor_gain	0.9600
10:103458226:C:CT	donor_gain	0.9600
10:103458224:GGC:G	donor_gain	0.9500
10:103455758:A:C	acceptor_gain	0.9400
10:103458227:C:CT	donor_gain	0.9400
10:103455758:A:AC	acceptor_gain	0.9200
10:103456414:A:C	acceptor_gain	0.8500
10:103455748:C:T	acceptor_gain	0.8200
10:103458195:A:AC	donor_gain	0.8200
10:103458196:C:CC	donor_gain	0.8200
10:103456252:A:AC	donor_gain	0.8100
10:103456253:C:CC	donor_gain	0.8100
10:103456253:CTTA:C	donor_gain	0.7900

AlphaMissense

2251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:103455623:T:A	E227V	0.999
10:103455385:C:A	W306C	0.998
10:103455385:C:G	W306C	0.998
10:103455553:G:C	F250L	0.998
10:103455553:G:T	F250L	0.998
10:103455555:A:G	F250L	0.998
10:103455575:G:T	A243D	0.998
10:103455577:A:C	F242L	0.998
10:103455577:A:T	F242L	0.998
10:103455579:A:G	F242L	0.998
10:103458659:A:C	S31R	0.998
10:103458659:A:T	S31R	0.998
10:103458661:T:G	S31R	0.998
10:103455588:C:G	A239P	0.997
10:103455598:G:C	C235W	0.997
10:103455610:G:C	F231L	0.997
10:103455610:G:T	F231L	0.997
10:103455612:A:G	F231L	0.997
10:103455622:C:A	E227D	0.997
10:103455622:C:G	E227D	0.997
10:103455623:T:G	E227A	0.997
10:103455738:A:G	W189R	0.997
10:103455738:A:T	W189R	0.997
10:103458387:C:A	G122V	0.997
10:103458412:A:G	W114R	0.997
10:103458412:A:T	W114R	0.997
10:103458420:G:T	P111H	0.997
10:103455387:A:G	W306R	0.996
10:103455387:A:T	W306R	0.996
10:103455550:G:C	F251L	0.996

dbSNP variants (sampled 300 via entrez): RS1001374955 (10:103458452 G>A,C), RS1001521433 (10:103457223 T>C), RS1002089128 (10:103458651 A>C), RS1002399695 (10:103453274 C>G), RS1002430066 (10:103453400 TTC>T), RS1002881870 (10:103453484 A>G), RS1003367996 (10:103454242 G>A), RS1003526367 (10:103459826 CT>C), RS1003554292 (10:103459371 G>A), RS1003585536 (10:103459648 G>A), RS1003694523 (10:103454853 C>T), RS1003808252 (10:103454589 G>C), RS1003865177 (10:103455977 G>A,C), RS1004482453 (10:103452807 T>C), RS1004582931 (10:103453199 T>C,G)

Disease associations

OMIM: gene MIM:612234 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002149_2	Schizophrenia	4.000000e-13
GCST008361_2	Response to cognitive-behavioural therapy in major depressive disorder	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases expression, decreases methylation	2
bisphenol A	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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