ADD2

Summary

ADD2 (adducin 2, HGNC:244) is a protein-coding gene on chromosome 2p13.3, encoding Beta-adducin (P35612). Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network.

Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 119 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_001617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:244
Approved symbol	ADD2
Name	adducin 2
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ADDB
Ensembl gene	ENSG00000075340
Ensembl biotype	protein_coding
OMIM	102681
Entrez	119

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000264436, ENST00000355733, ENST00000403045, ENST00000407644, ENST00000413157, ENST00000415348, ENST00000425976, ENST00000430656, ENST00000447731, ENST00000456320, ENST00000473232, ENST00000481675, ENST00000496178, ENST00000522886, ENST00000900356, ENST00000912686, ENST00000912687, ENST00000912688, ENST00000912689, ENST00000912690, ENST00000912691, ENST00000912692

RefSeq mRNA: 5 — MANE Select: NM_001617 NM_001185054, NM_001185055, NM_001617, NM_017482, NM_017488

CCDS: CCDS1906, CCDS1909, CCDS46318, CCDS54365

Canonical transcript exons

ENST00000264436 — 16 exons

Exon	Start	End
ENSE00000760576	70690786	70690929
ENSE00000760626	70704321	70704459
ENSE00000846514	70676796	70676885
ENSE00000846517	70677758	70677877
ENSE00000846519	70678704	70678961
ENSE00000846523	70683591	70683767
ENSE00000846524	70688024	70688122
ENSE00000846527	70692403	70692552
ENSE00000846529	70695721	70695801
ENSE00000846531	70696245	70696396
ENSE00001164065	70713066	70713184
ENSE00001733523	70656784	70663735
ENSE00001913240	70767886	70768200
ENSE00003539469	70706226	70706442
ENSE00003610350	70672878	70673006
ENSE00003784815	70674678	70674825

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 98.75.

FANTOM5 (CAGE): breadth broad, TPM avg 14.5313 / max 646.8794, expressed in 753 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29040	9.4687	681
29041	3.6581	544
29038	1.0053	88
29039	0.2448	130
29042	0.1543	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	98.75	gold quality
middle temporal gyrus	UBERON:0002771	98.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.54	gold quality
paraflocculus	UBERON:0005351	98.38	gold quality
cortical plate	UBERON:0005343	98.36	gold quality
frontal pole	UBERON:0002795	98.15	gold quality
CA1 field of hippocampus	UBERON:0003881	97.46	gold quality
postcentral gyrus	UBERON:0002581	97.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.13	gold quality
entorhinal cortex	UBERON:0002728	96.89	gold quality
superior frontal gyrus	UBERON:0002661	96.86	gold quality
orbitofrontal cortex	UBERON:0004167	96.51	gold quality
parietal lobe	UBERON:0001872	96.50	gold quality
middle frontal gyrus	UBERON:0002702	96.47	gold quality
ganglionic eminence	UBERON:0004023	96.17	gold quality
olfactory bulb	UBERON:0002264	94.55	gold quality
endothelial cell	CL:0000115	93.62	gold quality
primary visual cortex	UBERON:0002436	93.62	gold quality
ventricular zone	UBERON:0003053	93.61	gold quality
type B pancreatic cell	CL:0000169	93.09	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.78	gold quality
occipital lobe	UBERON:0002021	92.73	gold quality
cerebellum	UBERON:0002037	92.36	gold quality
cerebellar cortex	UBERON:0002129	91.74	gold quality
cerebellar hemisphere	UBERON:0002245	91.71	gold quality
frontal cortex	UBERON:0001870	91.37	gold quality
pons	UBERON:0000988	91.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.18	gold quality
neocortex	UBERON:0001950	90.92	gold quality
cerebral cortex	UBERON:0000956	90.70	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	413.32
E-CURD-112	yes	44.66
E-ANND-3	yes	7.60
E-MTAB-9067	yes	4.94
E-GEOD-99795	no	17.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting ADD2, 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-6740-5P	100.00	65.64	932
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119

Literature-anchored findings (GeneRIF, showing 15)

• there was significant heterogeneity between Slavic and Italian subjects in the phenotype-genotype relationships with beta-adducin (PMID:14553963)
• Expression of the hypertensive rat or human variant of adducin into normal renal epithelial cells recreates the hypertensive phenotype with higher Na+,K+-ATPase activity, mu2-subunit hyperphosphorylation, and impaired Na+,K+-ATPase endocytosis. (PMID:15528469)
• Polymorphisms in the ADD2 and ADD3 genes taken alone were not associated with blood pressure and renin activity (PMID:15716695)
• The very high levels of expression of ADD2 suggest that its promoter may be useful for directing erythroid-specific gene expression. (PMID:15963851)
• beta-adducin is a downstream target of and regulated by the PTN/RPTPbeta/zeta signaling pathway (PMID:16105548)
• Changes in intra-erythrocyte cations in ADD2 1797CC homozygous men might lead to osmotic fragility of erythrocytes, but to what extent they reflect systemic changes or are possibly involved in blood pressure regulation remains unknown. (PMID:17301826)
• hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients benefiting from antihypertensive drug therapies (PMID:17854487)
• ALPHA AND BETA ADDUCIN POLYMORPHISMS AFFECT DECLINE OF RENAL FUNCTION IN HUMAN IGA NEPHROPATHY. (PMID:19838659)
• phosphorylation of beta-adducin by GSK3 promotes efficient neurite outgrowth in neurons. (PMID:21606488)
• chorein interacts with beta-adducin and beta-actin. (PMID:24129186)
• Taken together, these results show that beta-adducin is a pivotal lipid raft-associated protein in PSGL-1-mediated neutrophil rolling on P-selectin. (PMID:25425738)
• ADD2 and NCX1 variants influence the risk and the clinical features of systemic lupus erythematosus and lupus nephritis. (PMID:26045217)
• Study evaluated effects of ADD genetic variability on cognitive functions in a sample of patients with schizophrenia, known to show a wide and heterogeneous neuropsychological deficit and found that ADD2 C1797T polymorphism showed diffuse effects on almost every cognitive domain. (PMID:26723519)
• Aberrant DNA methylation of ADD2 could be potential screening markers of colorectal cancer. (PMID:27493446)
• betaadducin was demonstrated to have a critical role in neutrophil migration. (PMID:29901076)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	add2	ENSDARG00000074581
mus_musculus	Add2	ENSMUSG00000030000
rattus_norvegicus	Add2	ENSRNOG00000015903
drosophila_melanogaster	hts	FBGN0263391
caenorhabditis_elegans		WBGENE00000073

Paralogs (2): ADD1 (ENSG00000087274), ADD3 (ENSG00000148700)

Protein

Protein identifiers

Beta-adducin — P35612 (reviewed: P35612)

Alternative names: Erythrocyte adducin subunit beta

All UniProt accessions (6): P35612, A0A1C7CYY0, C9J080, C9J299, C9JJK3, C9JTM0

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to the erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore provide a link between the spectrin cytoskeleton to the plasma membrane. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Found in a complex with ADD2, DMTN and SLC2A1. Interacts with SLC2A1.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane.

Tissue specificity. Expressed mainly in brain, spleen, kidney cortex and medulla, and heart. Also expressed in human umbilical vein endothelial cells, human vascular smooth muscle cells, kidney tubular cells and K-562 cell line.

Post-translational modifications. The N-terminus is blocked.

Domain organisation. Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.

Similarity. Belongs to the aldolase class II family. Adducin subfamily.

Isoforms (9)

UniProt ID	Names	Canonical?
P35612-1	1	yes
P35612-2	2, Adducin 63
P35612-3	3, Beta-4, E
P35612-4	4, Beta-4a
P35612-5	5, Beta-4b
P35612-6	6, Beta-4c
P35612-7	7, Beta-4d
P35612-8	8
P35612-9	9

RefSeq proteins (5): NP_001171983, NP_001171984, NP_001608, NP_059516, NP_059522 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001303	Aldolase_II/adducin_N	Domain
IPR036409	Aldolase_II/adducin_N_sf	Homologous_superfamily
IPR051017	Aldolase-II_Adducin_sf	Family

Pfam: PF00596

UniProt features (55 total): modified residue 27, splice variant 11, compositionally biased region 7, sequence variant 5, region of interest 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35612-F1	66.51	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.

Post-translational modifications (27): 11, 25, 55, 60, 344, 530, 532, 533, 535, 592, 596, 600, 604, 611, 613, 617, 619, 621, 675, 686 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5223345	Miscellaneous transport and binding events
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 210 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, MORF_RAGE, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GNF2_PRDX2, GOBP_SYNAPSE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, MODULE_16, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_CELL_CELL_ADHESION

GO Biological Process (8): synapse assembly (GO:0007416), actin cytoskeleton organization (GO:0030036), hemopoiesis (GO:0030097), leukocyte migration (GO:0050900), leukocyte tethering or rolling (GO:0050901), barbed-end actin filament capping (GO:0051016), actin filament bundle assembly (GO:0051017), protein-containing complex assembly (GO:0065003)

GO Molecular Function (11): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), calmodulin binding (GO:0005516), cytoskeletal adaptor activity (GO:0008093), protein kinase binding (GO:0019901), spectrin binding (GO:0030507), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), protein dimerization activity (GO:0046983), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (9): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), F-actin capping protein complex (GO:0008290), postsynaptic density (GO:0014069), cytoplasmic vesicle (GO:0031410), plasma membrane raft (GO:0044853), cytoplasm (GO:0005737), membrane (GO:0016020)

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
cytoskeletal protein binding	3
cellular anatomical structure	3
cytoskeleton organization	2
cellular component assembly	2
protein binding	2
protein-containing complex binding	2
protein dimerization activity	2
cytoplasm	2
nervous system development	1
cell junction assembly	1
synapse organization	1
actin filament-based process	1
cell development	1
immune system process	1
cell migration	1
cellular extravasation	1
leukocyte adhesion to vascular endothelial cell	1
actin filament capping	1
actin filament bundle organization	1
protein-containing complex organization	1
structural molecule activity	1
cytoskeleton	1
protein-macromolecule adaptor activity	1
kinase binding	1
identical protein binding	1
actin binding	1
binding	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
actin cytoskeleton	1
protein-containing complex	1
asymmetric synapse	1
postsynaptic specialization	1
intracellular vesicle	1
plasma membrane	1
membrane raft	1
plasma membrane region	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADD2	EPB41	P11171	993
ADD2	DMTN	Q08495	993
ADD2	ANK2	Q01484	977
ADD2	ANK1	P16157	976
ADD2	ANK3	Q12955	957
ADD2	TMOD4	Q9NZQ9	953
ADD2	TMOD1	P28289	947
ADD2	TMOD3	Q9NYL9	945
ADD2	TMOD2	Q9NZR1	943
ADD2	GYPC	P04921	902
ADD2	CALML3	P27482	796
ADD2	CALML6	Q8TD86	796
ADD2	CALML4	Q96GE6	796
ADD2	CALML5	Q9NZT1	795
ADD2	CALM1	P02593	786

IntAct

46 interactions, top by confidence:

A	B	Type	Score
ADD2	ADD1	psi-mi:“MI:0914”(association)	0.560
ADD1	ADD2	psi-mi:“MI:0915”(physical association)	0.560
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
DPPA4	ALOX12B	psi-mi:“MI:0914”(association)	0.530
SERPINB13	TTC4	psi-mi:“MI:0914”(association)	0.530
ANKRD29	ADD1	psi-mi:“MI:0914”(association)	0.530
DAPK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ABRA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DUSP23	DNM1L	psi-mi:“MI:0914”(association)	0.350
GNL2	POLR1G	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
LBH	DHX16	psi-mi:“MI:0914”(association)	0.350
ZNF641	ROCK2	psi-mi:“MI:0914”(association)	0.350
ADD2	ROCK2	psi-mi:“MI:0914”(association)	0.350
SALL1	MTA2	psi-mi:“MI:0914”(association)	0.350
CTAG2	PCNT	psi-mi:“MI:0914”(association)	0.350
INTS4	AP2A1	psi-mi:“MI:0914”(association)	0.350
CRISP3	ADD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (109): ADD2 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), ADD2 (Proximity Label-MS), ADD2 (Proximity Label-MS), NUDT12 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), ADD1 (Affinity Capture-MS), ADD3 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), ADD2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ3, A0M8T5, A4IG66, F1Q930, F7AEX0, O00750, O15327, O48832, O94876, P35612, P97578, Q00PJ1, Q05764, Q07E15, Q07E28, Q09YG9, Q0P4J3, Q155Q3, Q1JPG0, Q2QLA2, Q2T9N1, Q2TBG9, Q2VUH7, Q3ZC62, Q4R4D7, Q4V8E4, Q5BJ78, Q5BLE2, Q5JTW2, Q5R5V7, Q5RA60, Q5T1M5, Q69ZZ6, Q6GR21, Q6INU2, Q6IP02, Q6NTW1, Q8BG50, Q8C5W4, Q8C6E0

Diamond homologs: P35611, P35612, Q02645, Q05764, Q20952, Q5R5V7, Q5RA10, Q62847, Q63028, Q7LKY2, Q8GHB1, Q9A8Z4, Q9HYH5, Q9L9F0, Q9QYB5, Q9QYB8, Q9QYC0, Q9U9K0, Q9UEY8, Q9ZD54, A1AJA3, A7ZV69, A8A7U4, A9H8G1, A9N514, B1IT08, B1LQL8, B1XDU9, B1XPT3, B2TY70, B5BKK6, B5F3B4, B5Z2K4, B6I2A3, B7LCQ8, B7LLY0, B7M9G0, B7MLK3, B7MMH7, B7MSS8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKCA	down-regulates	ADD2	phosphorylation
PRKCZ	down-regulates	ADD2	phosphorylation
ADD2	“form complex”	“4.1 complex”	binding
PRKCD	unknown	ADD2	phosphorylation
PRKACA	“down-regulates activity”	ADD2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3251 predictions. Top by Δscore:

Variant	Effect	Δscore
2:70672871:GACTC:G	donor_loss	1.0000
2:70672872:ACTCA:A	donor_loss	1.0000
2:70672873:CTCA:C	donor_loss	1.0000
2:70672874:TCA:T	donor_loss	1.0000
2:70672875:C:CG	donor_loss	1.0000
2:70672876:A:AC	donor_gain	1.0000
2:70672876:A:C	donor_loss	1.0000
2:70672876:AC:A	donor_gain	1.0000
2:70672877:C:CC	donor_gain	1.0000
2:70672877:C:CT	donor_loss	1.0000
2:70672877:CC:C	donor_gain	1.0000
2:70672877:CCCT:C	donor_gain	1.0000
2:70673002:CTCTC:C	acceptor_gain	1.0000
2:70673003:TCTC:T	acceptor_gain	1.0000
2:70673004:CTC:C	acceptor_gain	1.0000
2:70673004:CTCC:C	acceptor_gain	1.0000
2:70673005:TC:T	acceptor_gain	1.0000
2:70673005:TCCT:T	acceptor_gain	1.0000
2:70673005:TCCTG:T	acceptor_loss	1.0000
2:70673006:CC:C	acceptor_gain	1.0000
2:70673006:CCTGA:C	acceptor_loss	1.0000
2:70673007:C:CC	acceptor_gain	1.0000
2:70674677:CCAT:C	donor_gain	1.0000
2:70674696:T:TA	donor_gain	1.0000
2:70676795:CCGGG:C	donor_gain	1.0000
2:70676884:AT:A	acceptor_gain	1.0000
2:70676885:TCTG:T	acceptor_loss	1.0000
2:70676886:C:CA	acceptor_loss	1.0000
2:70676886:C:CC	acceptor_gain	1.0000
2:70676888:G:C	acceptor_gain	1.0000

AlphaMissense

4793 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:70677806:A:C	F485L	1.000
2:70677806:A:T	F485L	1.000
2:70677808:A:G	F485L	1.000
2:70678790:A:G	W433R	1.000
2:70678790:A:T	W433R	1.000
2:70674748:G:C	F557L	0.999
2:70674748:G:T	F557L	0.999
2:70674749:A:C	F557C	0.999
2:70674749:A:G	F557S	0.999
2:70674750:A:G	F557L	0.999
2:70676881:C:G	R503P	0.999
2:70677764:C:A	R499S	0.999
2:70677764:C:G	R499S	0.999
2:70677807:A:C	F485C	0.999
2:70677807:A:G	F485S	0.999
2:70677877:A:G	W462R	0.999
2:70677877:A:T	W462R	0.999
2:70678788:C:A	W433C	0.999
2:70678788:C:G	W433C	0.999
2:70683601:A:G	L372P	0.999
2:70704443:A:G	L67P	0.999
2:70704455:A:G	F63S	0.999
2:70663464:G:C	F714L	0.998
2:70663464:G:T	F714L	0.998
2:70663466:A:G	F714L	0.998
2:70674716:T:G	Y568S	0.998
2:70674717:A:G	Y568H	0.998
2:70677765:C:G	R499T	0.998
2:70677875:C:A	W462C	0.998
2:70677875:C:G	W462C	0.998

dbSNP variants (sampled 300 via entrez): RS1000023958 (2:70671589 C>T), RS1000055079 (2:70671379 A>G), RS1000067782 (2:70755504 G>A,C), RS1000117222 (2:70715453 G>A), RS1000142601 (2:70709102 G>A), RS1000175533 (2:70708709 T>C), RS1000207057 (2:70665533 G>A), RS1000210162 (2:70749472 T>C), RS1000304086 (2:70677717 G>A,C,T), RS1000378553 (2:70743765 C>T), RS1000469573 (2:70715028 T>C), RS1000494384 (2:70665224 C>G), RS1000495489 (2:70666884 G>C), RS1000513059 (2:70710326 G>A), RS1000576299 (2:70703384 T>C)

Disease associations

OMIM: gene MIM:102681 | 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
GCST002481_1	Acne (severe)	5.000000e-06
GCST011398_37	Response to esketamine in treatment resistant depression	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009748	response to ketamine

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, affects cotreatment, decreases expression	6
bisphenol A	decreases expression	2
sodium arsenite	affects methylation, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
daidzein	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, decreases expression	1
aflatoxin B2	increases methylation	1
chromium hexavalent ion	decreases expression, increases abundance	1
glycitein	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
MT19c compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Vorinostat	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Manganese	decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

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