NGB

Summary

NGB (neuroglobin, HGNC:14077) is a protein-coding gene on chromosome 14q24.3, encoding Neuroglobin (Q9NPG2). Monomeric globin with a bis-histidyl six-coordinate heme-iron atom through which it can bind dioxygen, carbon monoxide and nitric oxide.

This gene encodes an oxygen-binding protein that is distantly related to members of the globin gene family. It is highly conserved among other vertebrates. It is expressed in the central and peripheral nervous system where it may be involved in increasing oxygen availability and providing protection under hypoxic/ischemic conditions.

Source: NCBI Gene 58157 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_021257

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14077
Approved symbol	NGB
Name	neuroglobin
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165553
Ensembl biotype	protein_coding
OMIM	605304
Entrez	58157

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000298352

RefSeq mRNA: 1 — MANE Select: NM_021257 NM_021257

CCDS: CCDS9856

Canonical transcript exons

ENST00000298352 — 4 exons

Exon	Start	End
ENSE00001094043	77265483	77266670
ENSE00001094044	77268466	77268585
ENSE00001094048	77269215	77269326
ENSE00001202356	77270849	77271206

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 87.21.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0736 / max 6.9550, expressed in 45 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144217	0.0439	23
144216	0.0297	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	87.21	gold quality
hypothalamus	UBERON:0001898	85.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.48	gold quality
endothelial cell	CL:0000115	83.84	silver quality
anterior cingulate cortex	UBERON:0009835	83.58	gold quality
frontal cortex	UBERON:0001870	83.51	gold quality
cingulate cortex	UBERON:0003027	83.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.43	gold quality
prefrontal cortex	UBERON:0000451	83.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.29	gold quality
superior frontal gyrus	UBERON:0002661	83.06	gold quality
neocortex	UBERON:0001950	82.55	gold quality
primary visual cortex	UBERON:0002436	81.11	gold quality
cerebral cortex	UBERON:0000956	79.45	gold quality
postcentral gyrus	UBERON:0002581	79.06	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.65	gold quality
buccal mucosa cell	CL:0002336	78.08	silver quality
middle temporal gyrus	UBERON:0002771	77.35	gold quality
secondary oocyte	CL:0000655	76.92	gold quality
pituitary gland	UBERON:0000007	76.70	gold quality
parietal lobe	UBERON:0001872	76.67	gold quality
amygdala	UBERON:0001876	76.64	gold quality
forebrain	UBERON:0001890	76.30	gold quality
adenohypophysis	UBERON:0002196	75.87	gold quality
telencephalon	UBERON:0001893	75.70	gold quality
occipital lobe	UBERON:0002021	75.43	gold quality
oocyte	CL:0000023	74.50	gold quality
temporal lobe	UBERON:0001871	74.23	gold quality
brain	UBERON:0000955	74.09	gold quality
tendon of biceps brachii	UBERON:0008188	72.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, EGR1, HIF1A, NFKB1, NFKB, REL, RELA, SP1, SP3

miRNA regulators (miRDB)

33 targeting NGB, 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-512-3P	99.97	67.35	1049
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-939-5P	97.10	65.80	1579

Literature-anchored findings (GeneRIF, showing 40)

• Full-length cDNA cloning and genomic organization of NGB have been reported. (PMID:11820779)
• Expression is induced by hemin in neural cells (PMID:12239161)
• an examination of the protein’s structure by crystallization and x-ray diffraction (PMID:12351835)
• human Ngb may be a novel oxidative stress-responsive sensor for signal transduction in the brain (PMID:12860983)
• results suggest a novel mechanism for the regulation of oxygen binding; contact with an appropriate electron donor would provoke the release of oxygen. Hence the oxygen affinity would be directly linked to the redox state of the cell. (PMID:14530264)
• His64 and Lys67 comprise a unique distal heme pocket in neuroglobin (PMID:14645216)
• Results are the first to demonstrate an interaction between neuroglobin (Ngb) and cystatin C. Ngb may modulate the intracellular transport (or secretion) of cystatin C to protect against neuronal death under conditions of oxidative stress. (PMID:15122877)
• Analysis of the neuroglobin genomic sequence identifies sequence motifs with similarity to the neuron-restrictive silencer element, possibly explaining a neuron-specific expression of neuroglobin. (PMID:15193759)
• oxygen binding in human neuroglobin and cytoglobin is allosterically regulated and temperature-dependent (PMID:15299006)
• Data show that wild-type human recombinant neuroglobin favors the F8His-Fe2+ -E7His conformation. (PMID:15488767)
• Identification of several residues that are crucial for several residues that are crucial for the Guanine nucleotide dissociation inhibitor activity of human Ngb. (PMID:15723537)
• TAT-Ngb is an efficient fusion protein capable of protecting the human islets in culture from loss of cell mass and function, thus increasing the quality of transplantable islets. (PMID:15808606)
• molecular characterization of human and Drosophila cytoglobulins and neuroglobulins (PMID:15819897)
• analysis of the proximal and distal histidine environment of cytoglobin and neuroglobin (PMID:16201751)
• Sites of interaction between Ngb and Galpha(i). (PMID:17337004)
• ferric-NGB acts not only as scavenger of toxic species, but also as a target of the self-generated reactive species (PMID:17600531)
• protein oxidation promotes stabilization of pentacoordinated species, thus favoring protein to adopt more reactive state & supporting existence of molecular mechanism where O2 is released under hypoxic conditions, suggesting O(2) storage function for Ngb. (PMID:17975837)
• These results clearly show that the GDI activity of human Ngb is tightly correlated with its neuroprotective activity. (PMID:18302932)
• both zebrafish and chimeric ZHHH Ngb can penetrate cell membranes in the absence of Chariot (PMID:18416560)
• A feature of Ngb is its heme hexacoordination in the absence of external ligands, observed both in the ferrous and in the ferric (met) forms. (PMID:18767815)
• Neuroglobin and cytoglobin are colocalized within human retinal neurons and retinal pigment epithelium but not within glial cells. (PMID:19001220)
• A significant association was found between Alzheimer disease risk and a variant in the NGB gene. Data is consistent with a model where women, older individuals and carriers of specific genotypes have lower levels of NGB leading to increased risk for AD. (PMID:19010568)
• Ngb polymorphism 89+104 t had protective effects on large-artery atherosclerosis and small-vessel occlusion in the Southern Chinese Han population (PMID:19087291)
• Structure determination by molecular replacement of neuroglobin at 1.8 A resolution showed the apparent space group was orthorhombic C222(1), but the real space group was monoclinic P2(1), due to twinning. It is a perfect hemihedrally twinned crystal. (PMID:19307722)
• Results demonstrate by immunohistochemical analysis the colocalization of neuroglobin and PrP(c) in the retinal ganglion cell layer. (PMID:19327369)
• neuroglobin transcript and protein are expressed in human glioblastoma cells, and this expression increases in hypoxia in vitro (PMID:19383366)
• The conformational and functional stability of Ngb at acidic pH was analyzed. (PMID:19860834)
• Ischemic stroke increases the expresssion of the neuroprotective protein neuroglobin in brain. (PMID:20075359)
• These data provides an explanation the action of neuroglobin in the protection of nerve cells from unwanted apoptosis. (PMID:20091232)
• The acid-induced denaturation pathway of apo-Ngb can be illustrated from the native state (N), via a partially unfolded state (U(A)) to the molten globule state (MG). (PMID:20227336)
• the haplotype block represented by rs3783988 in neuroglobin appears to influence recovery after severe traumatic brain injury (PMID:20345238)
• Ngb may confer protection against ischemia-reperfusion injury in the brain through its intrinsic antioxidant properties. (PMID:20571522)
• These data favor the hypothesis that the disulfide bond between Cys46 and Cys55 modulates the functioning of human neuroglobin. (PMID:20643048)
• There is a plausible central role for neuroglobin in the control of apoptosis. (PMID:21190290)
• neuroglobin may function as a physiological oxidative stress sensor and a post-translationally redox-regulated nitrite reductase that generates NO under six-to-five-coordinate heme pocket control (PMID:21296891)
• Cimeric Myoglobin has a cell-membrane-penetrating activity similar to zebrafish Ngb. (PMID:21304818)
• Data suggest a potential role of DNA methylation in regulating NGB tissue-specific expression. (PMID:21362510)
• overexpression in non-small cell lung cancer is associated with histological subtype, hypoxia (PMID:21601304)
• This review describes the discovery of neuroglobin over a decade ago, its structure, affinity for oxygen, and its expression in cerebral neurons, all of which suggest it plays a role in providing oxygen to the brain. (PMID:21620833)
• Caenorhabditis elegans globin GLB-26 (expressed from gene T22C1.2) has been studied in comparison with human neuroglobin (Ngb) and cytoglobin (Cygb) for its electron transfer properties (PMID:21674044)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ngb	ENSDARG00000053475
mus_musculus	Ngb	ENSMUSG00000021032
rattus_norvegicus	Ngb	ENSRNOG00000011719

Protein

Protein identifiers

Neuroglobin — Q9NPG2 (reviewed: Q9NPG2)

Alternative names: Nitrite reductase

All UniProt accessions (2): A0M8W9, Q9NPG2

UniProt curated annotations — full annotation on UniProt →

Function. Monomeric globin with a bis-histidyl six-coordinate heme-iron atom through which it can bind dioxygen, carbon monoxide and nitric oxide. Could help transport oxygen and increase its availability to the metabolically active neuronal tissues, though its low quantity in tissues as well as its high affinity for dioxygen, which may limit its oxygen-releasing ability, argue against it. The ferrous/deoxygenated form exhibits a nitrite reductase activity and it could produce nitric oxide which in turn inhibits cellular respiration in response to hypoxia. In its ferrous/deoxygenated state, it may also exhibit GDI (Guanine nucleotide Dissociation Inhibitor) activity toward heterotrimeric G-alpha proteins, thereby regulating signal transduction to facilitate neuroprotective responses in the wake of hypoxia and associated oxidative stress.

Subunit / interactions. Monomer. Homodimer and homotetramer; disulfide-linked. Mainly monomeric but also detected as part of homodimers and homotetramers. Interacts with 14-3-3 proteins; regulates the phosphorylation of NGB. Could interact (ferrous form) with G-alpha(i) proteins (GTP-bound form).

Subcellular location. Cytoplasm. Cytosol. Mitochondrion matrix.

Tissue specificity. Predominantly expressed in brain, the strongest expression is seen in the frontal lobe, the subthalamic nucleus and the thalamus.

Post-translational modifications. Phosphorylated during hypoxia by ERK1/ERK2. Phosphorylation regulates the heme pocket hexacoordination preventing the association of His-64 with the heme metal center. Thereby, promotes the access of dioxygen and nitrite to the heme and stimulates the nitrite reductase activity. Phosphorylation during hypoxia is stabilized by 14-3-3 proteins. An intramolecular Cys-46/Cys-55 disulfide bond, not necessarily present in orthologs, regulates the heme pocket hexacoordination preventing the association of His-64 with the heme metal center. Thereby, promotes the access of dioxygen and nitrite to the heme and stimulates the nitrite reductase activity.

Similarity. Belongs to the globin family.

RefSeq proteins (1): NP_067080* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000971	Globin	Domain
IPR009050	Globin-like_sf	Homologous_superfamily
IPR012292	Globin/Proto	Homologous_superfamily
IPR050532	Globin-like_OT	Family

Pfam: PF00042

Catalyzed reactions (Rhea), 1 shown:

• Fe(III)-heme b-[protein] + nitric oxide + H2O = Fe(II)-heme b-[protein] + nitrite + 2 H(+) (RHEA:77711)

UniProt features (25 total): helix 11, mutagenesis site 8, binding site 2, chain 1, domain 1, turn 1, disulfide bond 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7VQG	X-RAY DIFFRACTION	1.35
8WUB	X-RAY DIFFRACTION	1.5
4MPM	X-RAY DIFFRACTION	1.74
1OJ6	X-RAY DIFFRACTION	1.95
8GRZ	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPG2-F1	95.09	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 64 (distal binding residue; reversible); 96 (proximal binding residue)

Disulfide bonds (1): 46–55

Mutagenesis-validated functional residues (8):

Position	Phenotype
55	loss of intramolecular disulfide bond.
64	increased nitrite reductase activity.
120	no effect on disulfide bond.
17	no effect on interaction with 14-3-3 proteins.
46	decreased nitrite reductase activity.
46	loss of intramolecular disulfide bond.
50	decreased interaction with 14-3-3 proteins.
55	decreased affinity for nitrite. decreased nitrite reductase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8981607	Intracellular oxygen transport

MSigDB gene sets: 55 (showing top): chr14q24, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, AML_Q6, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOBP_GAS_TRANSPORT, GOBP_OXYGEN_TRANSPORT, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, AML1_01, DANG_BOUND_BY_MYC, GOMF_OXYGEN_BINDING, GOCC_MITOCHONDRIAL_MATRIX, BENPORATH_MYC_MAX_TARGETS, GOMF_GDP_DISSOCIATION_INHIBITOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY

GO Biological Process (3): response to hypoxia (GO:0001666), oxygen transport (GO:0015671), cellular response to hypoxia (GO:0071456)

GO Molecular Function (8): GDP-dissociation inhibitor activity (GO:0005092), oxygen carrier activity (GO:0005344), oxygen binding (GO:0019825), heme binding (GO:0020037), metal ion binding (GO:0046872), nitrite reductase activity (GO:0098809), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): mitochondrial matrix (GO:0005759), cytosol (GO:0005829), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
gas transport	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
GDP binding	1
GTPase regulator activity	1
oxygen transport	1
oxygen binding	1
molecular carrier activity	1
small molecule binding	1
tetrapyrrole binding	1
cation binding	1
oxidoreductase activity, acting on other nitrogenous compounds as donors	1
binding	1
catalytic activity	1
mitochondrion	1
intracellular organelle lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NGB	CYGB	Q8WWM9	975
NGB	MB	P02144	964
NGB	CYCS	P00001	939
NGB	ADGB	Q8N7X0	846
NGB	FLOT1	O75955	773
NGB	RHOA	P06749	636
NGB	CYB5B	O43169	633
NGB	CYB5A	P00167	632
NGB	IDE	P14735	619
NGB	GBE1	Q04446	608
NGB	HBB	P02023	543
NGB	HIF1A	Q16665	541
NGB	AHSP	Q9NZD4	540
NGB	APOE	P02649	491
NGB	GPX5	O75715	489
NGB	GPX2	P18283	489

IntAct

59 interactions, top by confidence:

A	B	Type	Score
NGB	TDO2	psi-mi:“MI:0915”(physical association)	0.720
VAC14	NGB	psi-mi:“MI:0915”(physical association)	0.720
NGB	IHO1	psi-mi:“MI:0915”(physical association)	0.720
TDO2	NGB	psi-mi:“MI:0915”(physical association)	0.720
NGB	VAC14	psi-mi:“MI:0915”(physical association)	0.720
IHO1	NGB	psi-mi:“MI:0915”(physical association)	0.720
NGB	REL	psi-mi:“MI:0915”(physical association)	0.560
NGB	C1orf94	psi-mi:“MI:0915”(physical association)	0.560
NGB	L3MBTL3	psi-mi:“MI:0915”(physical association)	0.560
REL	NGB	psi-mi:“MI:0915”(physical association)	0.560
L3MBTL3	NGB	psi-mi:“MI:0915”(physical association)	0.560
NGB	MEI4	psi-mi:“MI:0915”(physical association)	0.560
GATAD2B	NGB	psi-mi:“MI:0915”(physical association)	0.560
NIF3L1	NGB	psi-mi:“MI:0915”(physical association)	0.560
BTBD2	NGB	psi-mi:“MI:0915”(physical association)	0.560
DDIT4L	NGB	psi-mi:“MI:0915”(physical association)	0.560
MEI4	NGB	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	NGB	psi-mi:“MI:0915”(physical association)	0.560
ZNF655	NGB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (169): NGB (Two-hybrid), NGB (Two-hybrid), NGB (Two-hybrid), L3MBTL3 (Two-hybrid), C1orf94 (Two-hybrid), CCDC36 (Two-hybrid), AKT1 (FRET), NGB (Reconstituted Complex), NGB (Reconstituted Complex), MPP2 (Affinity Capture-MS), TRIM32 (Affinity Capture-MS), CCNB1 (Affinity Capture-MS), NGB (Reconstituted Complex), GNAO1 (Reconstituted Complex), NGB (Synthetic Lethality)

ESM2 similar proteins: A4FV98, A5D7B1, A6NFX1, D3ZVU9, O00764, O08557, O35083, O43488, O46560, O73884, O94760, O95848, P82197, Q05B60, Q0II59, Q0P5C0, Q0P5M9, Q0VD18, Q14728, Q29081, Q3KN66, Q3KRA9, Q3U129, Q3UGX3, Q3ZBF0, Q4PS77, Q5I0D5, Q5SUV1, Q64380, Q67FW5, Q6GV29, Q6WZ20, Q8CIW5, Q8K2U2, Q8R2H9, Q8TCT1, Q8VCE6, Q95JH0, Q95JH2, Q96AZ1

Diamond homologs: A0A072TK64, I3SX86, O66586, P02239, P02240, P04252, P23244, P24232, P26353, P39662, P39676, P40609, P49852, Q3KN66, Q47266, Q54D73, Q57LF5, Q59MV9, Q5PIH6, Q6D245, Q6EV97, Q6HLA6, Q6LM37, Q6WZ17, Q6WZ18, Q6WZ19, Q6WZ20, Q73B49, Q7ABK6, Q7C0F9, Q7MH09, Q7N215, Q7NSD8, Q7TTP0, Q7TTP2, Q7UIY1, Q7WHW5, Q7WUM8, Q81FW4, Q81T23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

975 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77268504:T:TA	donor_gain	1.0000
14:77269209:TCTCA:T	donor_loss	1.0000
14:77269210:CTCAC:C	donor_loss	1.0000
14:77269211:TCAC:T	donor_loss	1.0000
14:77269212:CA:C	donor_loss	1.0000
14:77269213:ACCTT:A	donor_gain	1.0000
14:77269214:CCT:C	donor_loss	1.0000
14:77269214:CCTTC:C	donor_gain	1.0000
14:77269217:T:A	donor_gain	1.0000
14:77269323:CAGC:C	acceptor_gain	1.0000
14:77270843:CCTCA:C	donor_loss	1.0000
14:77270844:CTCA:C	donor_loss	1.0000
14:77270845:TCAC:T	donor_loss	1.0000
14:77270846:CAC:C	donor_loss	1.0000
14:77266667:CTGT:C	acceptor_gain	0.9900
14:77268491:A:AC	donor_gain	0.9900
14:77268492:C:CC	donor_gain	0.9900
14:77268582:TCAC:T	acceptor_gain	0.9900
14:77268583:CAC:C	acceptor_gain	0.9900
14:77268583:CACC:C	acceptor_gain	0.9900
14:77268586:C:CC	acceptor_gain	0.9900
14:77268590:C:CT	acceptor_gain	0.9900
14:77269325:GC:G	acceptor_gain	0.9900
14:77269326:CC:C	acceptor_gain	0.9900
14:77269327:C:CC	acceptor_gain	0.9900
14:77269328:T:A	acceptor_loss	0.9900
14:77270848:CCTGG:C	donor_gain	0.9900
14:77266538:A:AC	donor_gain	0.9800
14:77266539:C:CC	donor_gain	0.9800
14:77268457:TTTAC:T	donor_loss	0.9800

AlphaMissense

971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77269290:G:C	F42L	0.997
14:77269290:G:T	F42L	0.997
14:77269292:A:G	F42L	0.997
14:77266595:A:G	W133R	0.996
14:77266595:A:T	W133R	0.996
14:77268509:C:T	G93D	0.996
14:77268501:G:C	H96D	0.995
14:77269291:A:G	F42S	0.995
14:77270854:A:C	F28L	0.995
14:77270854:A:T	F28L	0.995
14:77270856:A:G	F28L	0.995
14:77266593:C:A	W133C	0.994
14:77266593:C:G	W133C	0.994
14:77269234:A:G	F61S	0.994
14:77268509:C:A	G93V	0.993
14:77270867:C:T	G24D	0.993
14:77266654:A:G	L113P	0.992
14:77268501:G:T	H96N	0.992
14:77269224:G:C	H64Q	0.992
14:77269224:G:T	H64Q	0.992
14:77270868:C:G	G24R	0.992
14:77266657:G:A	S112F	0.991
14:77268510:C:G	G93R	0.991
14:77268563:G:T	A75E	0.991
14:77269226:G:C	H64D	0.991
14:77269291:A:C	F42C	0.991
14:77268469:G:C	F106L	0.990
14:77268469:G:T	F106L	0.990
14:77268471:A:G	F106L	0.990
14:77268499:G:C	H96Q	0.990

dbSNP variants (sampled 300 via entrez): RS1000009936 (14:77267347 C>A,G), RS1000055334 (14:77269720 C>G,T), RS1000841511 (14:77271210 C>A), RS1001299686 (14:77271651 C>CG), RS1001417178 (14:77265797 C>T), RS1001482008 (14:77265637 C>T), RS1002068340 (14:77268936 T>A,G), RS1002455198 (14:77267155 A>G), RS1002568109 (14:77265017 C>T), RS1002893275 (14:77266821 A>G), RS1002924588 (14:77265357 C>A), RS1003356407 (14:77269898 T>C), RS1003629551 (14:77269756 T>C), RS1004300500 (14:77273134 T>C), RS1004682293 (14:77269065 C>G)

Disease associations

OMIM: gene MIM:605304 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
bisphenol A	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
MC1568	affects binding, decreases reaction, decreases expression, increases expression	1
Calcium	affects transport	1
Chlorine	affects abundance	1
Copper	decreases uptake	1
Diethylhexyl Phthalate	affects binding, decreases reaction, decreases expression	1
Iron	decreases uptake	1
Lead	affects expression	1
Ozone	increases expression	1
Paraquat	increases abundance, decreases reaction, increases response to substance	1
Potassium	affects abundance	1
Rotenone	decreases expression	1
Sulfur	affects abundance	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases uptake	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Reactive Oxygen Species	increases response to substance, decreases reaction, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0U0	SH-SY5Y-FLAG-NGB	Cancer cell line	Female

Clinical trials (associated diseases)

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