APBB2

Summary

APBB2 (amyloid beta precursor protein binding family B member 2, HGNC:582) is a protein-coding gene on chromosome 4p14-p13, encoding Amyloid beta precursor protein binding family B member 2 (Q92870). Plays a role in the maintenance of lens transparency, and may also play a role in muscle cell strength.

The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta (A4) precursor-like protein 2. This protein contains two phosphotyrosine binding (PTB) domains, which are thought to function in signal transduction. Polymorphisms in this gene have been associated with Alzheimer’s disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 323 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 145 total — 2 pathogenic
• MANE Select transcript: NM_004307

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:582
Approved symbol	APBB2
Name	amyloid beta precursor protein binding family B member 2
Location	4p14-p13
Locus type	gene with protein product
Status	Approved
Aliases	FE65L, FE65L1, MGC35575
Ensembl gene	ENSG00000163697
Ensembl biotype	protein_coding
OMIM	602710
Entrez	323

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 25 protein_coding, 6 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000295974, ENST00000502682, ENST00000502687, ENST00000502841, ENST00000503264, ENST00000503503, ENST00000503555, ENST00000504305, ENST00000504484, ENST00000505266, ENST00000506352, ENST00000506999, ENST00000507831, ENST00000508593, ENST00000508676, ENST00000508707, ENST00000509446, ENST00000509475, ENST00000510670, ENST00000510925, ENST00000511120, ENST00000511572, ENST00000512510, ENST00000513140, ENST00000513493, ENST00000513516, ENST00000513611, ENST00000514094, ENST00000514920, ENST00000894650, ENST00000894651, ENST00000894652, ENST00000894653, ENST00000912361, ENST00000912362, ENST00000971607, ENST00000971608

RefSeq mRNA: 9 — MANE Select: NM_004307 NM_001166050, NM_001166051, NM_001166052, NM_001166053, NM_001166054, NM_001330656, NM_001330658, NM_004307, NM_173075

CCDS: CCDS43224, CCDS54760, CCDS54761, CCDS54762, CCDS82918

Canonical transcript exons

ENST00000508593 — 18 exons

Exon	Start	End
ENSE00001122478	41013583	41014398
ENSE00001169516	40935077	40935139
ENSE00001308464	41033236	41033304
ENSE00001330720	41065576	41065673
ENSE00001364083	40810027	40816259
ENSE00001418703	41100639	41100750
ENSE00001421325	41142987	41143142
ENSE00002056300	40944865	40945073
ENSE00002087412	41214405	41214542
ENSE00003478102	40821871	40822050
ENSE00003495942	40827132	40827219
ENSE00003529806	40934614	40934699
ENSE00003537900	40890364	40890491
ENSE00003540410	40830463	40830577
ENSE00003594374	40893265	40893411
ENSE00003598343	40825887	40825970
ENSE00003694536	40934456	40934516
ENSE00003789022	40823644	40823759

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0410 / max 297.2931, expressed in 1663 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51932	19.3826	1610
51933	4.5717	1410
51926	2.4695	410
51935	2.0084	942
51934	1.2964	736
51931	0.8817	604
51938	0.5661	308
51939	0.5062	286
51936	0.2873	133
51937	0.0711	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.49	gold quality
calcaneal tendon	UBERON:0003701	97.42	gold quality
sural nerve	UBERON:0015488	96.65	gold quality
tendon	UBERON:0000043	95.16	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.90	gold quality
inferior olivary complex	UBERON:0002127	94.64	gold quality
tendon of biceps brachii	UBERON:0008188	94.10	silver quality
medial globus pallidus	UBERON:0002477	93.48	gold quality
ventricular zone	UBERON:0003053	93.35	gold quality
corpus callosum	UBERON:0002336	93.21	gold quality
tibia	UBERON:0000979	92.85	gold quality
colonic epithelium	UBERON:0000397	92.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.61	gold quality
nerve	UBERON:0001021	92.36	gold quality
tibial nerve	UBERON:0001323	92.36	gold quality
metanephric glomerulus	UBERON:0004736	92.25	gold quality
renal glomerulus	UBERON:0000074	92.05	gold quality
skin of hip	UBERON:0001554	91.93	gold quality
right ovary	UBERON:0002118	91.66	gold quality
globus pallidus	UBERON:0001875	91.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.51	gold quality
spinal cord	UBERON:0002240	91.32	gold quality
left ovary	UBERON:0002119	91.29	gold quality
decidua	UBERON:0002450	91.24	gold quality
ascending aorta	UBERON:0001496	91.23	gold quality
thoracic aorta	UBERON:0001515	91.22	gold quality
adipose tissue	UBERON:0001013	91.14	gold quality
thyroid gland	UBERON:0002046	91.12	gold quality
stromal cell of endometrium	CL:0002255	91.05	gold quality
connective tissue	UBERON:0002384	91.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1959.78
E-CURD-119	yes	67.35
E-ANND-3	yes	10.67

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TYMS	Repression

miRNA regulators (miRDB)

298 targeting APBB2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-512-3P	99.97	67.35	1049

Literature-anchored findings (GeneRIF, showing 13)

• FE65L1 potentiates gamma-secretase processing of APP CTFs. This requires binding of FE65L1 to APP and APP CTFs. Enhanced APP CTF processing can be detected in early endosome vesicles (PMID:14527950)
• rs13133980 associated significantly with age of onset in Alzheimer disease. Genetic variations in APBB2 may affect late onset AD susceptibility. (PMID:15714520)
• the apoptosis inhibitory domain of FE65-like protein 1 regulates both apoptotic and caspase-independent programmed cell death mediated by TNF (PMID:16083851)
• In response to TNF, Zfra is upregulated and modulates TNF-mediated cell death via interacting with TRADD, FADD and RIP (death-inducing signaling complex) at the receptor level, and downstream effectors NF-kappaB, p53, WOX1, and JNK1. (PMID:17567906)
• The hCV1558625 G allele was over-represented in patients with onset under age 70 compared to controls in the same age range. (PMID:18852029)
• The differential processing of amyloid-beta precursor via secretase enzymes regulates the proliferation and differentiation of human embryonic stem cell. (PMID:19542221)
• The APBB2 rs13133980 G allele was over-represented in centenarians with severe cognitive impairment compared to individuals without this disability. (PMID:23384821)
• results provide additional evidence of a genetic interaction between GSK3beta and APBB2 and further suggest that GSK3beta is involved in the pathophysiology of both of the primary neuropathologies of Alzheimer’s disease (PMID:26194614)
• APBB2 was differentially expressed between Fibromyalgia patients and healthy controls. (PMID:27157394)
• Genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients under methadone maintenance treatment. The haplotype combinations further confirmed this observation, especially in the patients with a positive urine morphine test result. The major genotype and allele type carriers showed a two-time higher risk of amphetamine use than the minor allele type carriers. (PMID:29330135)
• In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. (PMID:31688885)
• miR2053p promotes lung cancer progression by targeting APBB2. (PMID:34165160)
• Hsa-miR-30a-3p attenuates gastric adenocarcinoma proliferation and metastasis via APBB2. (PMID:34182542)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000103290
mus_musculus	Apbb2	ENSMUSG00000029207
rattus_norvegicus	Apbb2	ENSRNOG00000063717
caenorhabditis_elegans		WBGENE00001410

Paralogs (2): APBB3 (ENSG00000113108), APBB1 (ENSG00000166313)

Protein

Protein identifiers

Amyloid beta precursor protein binding family B member 2 — Q92870 (reviewed: Q92870)

Alternative names: Amyloid-beta (A4) precursor protein-binding family B member 2, Protein Fe65-like 1

All UniProt accessions (14): Q92870, A0A1D5RMR3, D6RAE0, D6RAJ4, D6RB00, D6RB55, D6RD19, D6RDY3, D6RGD4, G5E9Y1, H0Y943, H0Y9U9, H0YA92, H0YAJ5

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the maintenance of lens transparency, and may also play a role in muscle cell strength. Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning. Activates transcription of APP.

Subunit / interactions. Interacts (via C-terminus) with APP (via C-terminus). Interacts with APLP2 (via cytoplasmic domain).

Subcellular location. Endoplasmic reticulum. Golgi apparatus. Early endosome.

Tissue specificity. Widely expressed.

Isoforms (4)

UniProt ID	Names	Canonical?
Q92870-1	1	yes
Q92870-2	2
Q92870-3	3
Q92870-4	4

RefSeq proteins (9): NP_001159522, NP_001159523, NP_001159524, NP_001159525, NP_001159526, NP_001317585, NP_001317587, NP_004298, NP_775098 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR039576	APBB1/2/3	Family

Pfam: PF00397, PF00640

UniProt features (24 total): modified residue 5, compositionally biased region 4, splice variant 4, region of interest 4, domain 3, chain 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92870-F1	61.73	0.30

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 (5): 123, 160, 334, 409, 412

Mutagenesis-validated functional residues (1):

Position	Phenotype
702	abolishes interaction with app and gamma-secretase-dependent processing of the app membrane-anchored c-terminal fragment

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 301 (showing top): GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_CELL_JUNCTION_ORGANIZATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_MUSCLE_CONTRACTION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, GOBP_SMOOTH_MUSCLE_CONTRACTION

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), neuron migration (GO:0001764), regulation of DNA-templated transcription (GO:0006355), smooth muscle contraction (GO:0006939), axon guidance (GO:0007411), extracellular matrix organization (GO:0030198), intracellular signal transduction (GO:0035556), maintenance of lens transparency (GO:0036438), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of transcription by RNA polymerase II (GO:0045944), synapse organization (GO:0050808), negative regulation of cell cycle phase transition (GO:1901988)

GO Molecular Function (3): amyloid-beta binding (GO:0001540), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), lamellipodium (GO:0030027), growth cone (GO:0030426), synapse (GO:0045202), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
endomembrane system	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
intracellular anatomical structure	2
apoptotic process	2
regulation of apoptotic process	2
binding	2
cellular anatomical structure	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
cell migration	1
generation of neurons	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
muscle contraction	1
axonogenesis	1
neuron projection guidance	1
extracellular structure organization	1
external encapsulating structure organization	1
signal transduction	1
tissue homeostasis	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
positive regulation of DNA-templated transcription	1
cell junction organization	1
negative regulation of cell cycle process	1
cell cycle phase transition	1
regulation of cell cycle phase transition	1
peptide binding	1
molecular_function	1
endosome	1
cell leading edge	1
plasma membrane bounded cell projection	1
site of polarized growth	1
distal axon	1
cell junction	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1719 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APBB2	APP	P05067	966
APBB2	APBA2	Q99767	824
APBB2	APBA1	Q02410	803
APBB2	APLP2	Q06481	748
APBB2	APLP1	P51693	691
APBB2	XPNPEP2	O43895	560
APBB2	CYP46A1	Q9Y6A2	519
APBB2	STXBP1	P61764	506
APBB2	KAT5	Q92993	505
APBB2	ACE	P12821	486
APBB2	BLMH	Q13867	474
APBB2	ABCA2	Q9BZC7	455
APBB2	APBB3	O95704	452
APBB2	KCNG2	Q9UJ96	448
APBB2	GAB2	Q9UQC2	439

IntAct

38 interactions, top by confidence:

A	B	Type	Score
APBB2	APP	psi-mi:“MI:0914”(association)	0.830
APBB2	APP	psi-mi:“MI:0915”(physical association)	0.830
EGFR	APBB2	psi-mi:“MI:0915”(physical association)	0.740
APBB2	EGFR	psi-mi:“MI:0407”(direct interaction)	0.740
EGFR	APBB2	psi-mi:“MI:0407”(direct interaction)	0.740
APLP2	APBB2	psi-mi:“MI:0915”(physical association)	0.670
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
LDHAL6B	MTIF2	psi-mi:“MI:0914”(association)	0.530
TOR1A	TOR1B	psi-mi:“MI:0914”(association)	0.530
APBB2	HTT	psi-mi:“MI:0915”(physical association)	0.370
HTT	APBB2	psi-mi:“MI:0915”(physical association)	0.370
APP	RTL1	psi-mi:“MI:0914”(association)	0.350
APBB2	APBB1	psi-mi:“MI:0914”(association)	0.350
QTRT1	APBB1	psi-mi:“MI:0914”(association)	0.350
ASIP	ATRN	psi-mi:“MI:0914”(association)	0.350
WFDC8	ACTA2	psi-mi:“MI:0914”(association)	0.350
CCN6	CRELD2	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SYDE1	APBB1	psi-mi:“MI:0914”(association)	0.350
QTRT1	ACSL4	psi-mi:“MI:0914”(association)	0.350
AQP12B	TIPRL	psi-mi:“MI:0914”(association)	0.350
APBB2	LAMTOR5	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): APBB2 (Two-hybrid), HSPA8 (Affinity Capture-MS), TBC1D4 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), APP (Affinity Capture-MS), APLP2 (Affinity Capture-MS), APBB1 (Affinity Capture-MS), AKAP1 (Affinity Capture-MS), GOPC (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), APLP1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), APOL2 (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS), SYDE2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HU22, A1A5R8, A8K979, B8A5Y1, E1BB03, F6UH96, O75113, P62283, P62285, P62286, P62287, P62288, P62289, P62290, P62291, P62292, P62293, P62294, P62296, P62297, Q08AX9, Q3MHN7, Q3US16, Q5BKS4, Q5HZL1, Q5XKL5, Q5ZIX8, Q5ZLE9, Q64702, Q68FF0, Q6A037, Q6IE81, Q6NQ79, Q6NSI8, Q6NZP1, Q6PCM1, Q8BMI4, Q8BVE8, Q8BZ05, Q8CJ27

Diamond homologs: O00213, O35827, O95704, P46933, Q8R1C9, Q92870, Q9BKZ9, Q9DBR4, Q9QXJ1, E9Q5F9, Q9BYW2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PIP3 activates AKT signaling	5	13.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
axonogenesis	5	27.7×	4e-04
positive regulation of ERK1 and ERK2 cascade	5	14.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	111
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2506554	GRCh37/hg19 4p14-13(chr4:40337485-41941400)	Pathogenic
253447	GRCh37/hg19 4p14-11(chr4:38532827-49064044)x3	Pathogenic

SpliceAI

6756 predictions. Top by Δscore:

Variant	Effect	Δscore
4:40816255:CGTAA:C	acceptor_gain	1.0000
4:40816256:GTAA:G	acceptor_gain	1.0000
4:40816257:TAA:T	acceptor_gain	1.0000
4:40816258:AA:A	acceptor_gain	1.0000
4:40816258:AACT:A	acceptor_loss	1.0000
4:40816259:AC:A	acceptor_loss	1.0000
4:40816260:C:A	acceptor_loss	1.0000
4:40816260:C:CC	acceptor_gain	1.0000
4:40821866:CTCAC:C	donor_loss	1.0000
4:40821868:CA:C	donor_loss	1.0000
4:40821869:A:AC	donor_gain	1.0000
4:40821870:C:CA	donor_loss	1.0000
4:40821870:C:CC	donor_gain	1.0000
4:40822047:CATT:C	acceptor_gain	1.0000
4:40822049:TT:T	acceptor_gain	1.0000
4:40822051:C:CC	acceptor_gain	1.0000
4:40823638:TCTCA:T	donor_loss	1.0000
4:40823640:TCA:T	donor_loss	1.0000
4:40823643:C:G	donor_loss	1.0000
4:40823755:CATTC:C	acceptor_gain	1.0000
4:40823757:TTC:T	acceptor_gain	1.0000
4:40823758:TC:T	acceptor_gain	1.0000
4:40823759:CC:C	acceptor_gain	1.0000
4:40823759:CCTGG:C	acceptor_loss	1.0000
4:40823760:C:CC	acceptor_gain	1.0000
4:40823761:T:A	acceptor_loss	1.0000
4:40825886:CCGA:C	donor_gain	1.0000
4:40825966:ATCTA:A	acceptor_gain	1.0000
4:40825968:CTA:C	acceptor_gain	1.0000
4:40825969:TA:T	acceptor_gain	1.0000

AlphaMissense

5016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:40830469:G:C	C545W	1.000
4:40830470:C:T	C545Y	1.000
4:40830471:A:G	C545R	1.000
4:40830480:G:C	H542D	1.000
4:40830482:A:G	L541P	1.000
4:40830482:A:T	L541H	1.000
4:40830491:G:T	A538D	1.000
4:40830494:A:C	I537S	1.000
4:40830494:A:T	I537N	1.000
4:40830503:G:T	A534E	1.000
4:40830514:A:C	C530W	1.000
4:40830515:C:T	C530Y	1.000
4:40830516:A:G	C530R	1.000
4:40830518:C:G	R529P	1.000
4:40830520:A:C	F528L	1.000
4:40830520:A:T	F528L	1.000
4:40830521:A:C	F528C	1.000
4:40830521:A:G	F528S	1.000
4:40830522:A:C	F528V	1.000
4:40830522:A:G	F528L	1.000
4:40830524:A:T	V527E	1.000
4:40830528:G:C	H526D	1.000
4:40830529:A:C	C525W	1.000
4:40830530:C:G	C525S	1.000
4:40830530:C:T	C525Y	1.000
4:40830531:A:G	C525R	1.000
4:40830531:A:T	C525S	1.000
4:40830561:C:G	A515P	1.000
4:40830563:A:T	V514E	1.000
4:40830567:A:C	Y513D	1.000

dbSNP variants (sampled 300 via entrez): RS10000108 (4:40908479 C>T), RS1000032436 (4:40862668 G>C), RS1000045187 (4:41166349 C>T), RS1000049343 (4:41117933 G>A), RS10000647 (4:41092112 A>G), RS1000065606 (4:40952863 T>A), RS1000074926 (4:40975543 C>G), RS10000791 (4:40967048 A>G), RS1000084056 (4:41161085 G>A,C), RS1000088388 (4:40868652 C>T), RS1000088486 (4:41055919 G>A), RS1000088802 (4:41122224 T>C), RS1000098468 (4:41028076 T>C,G), RS10001069 (4:41109300 C>T), RS1000135041 (4:40908261 A>G,T)

Disease associations

OMIM: gene MIM:602710 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001786_14	Dental caries	8.000000e-06
GCST002235_1	Opioid sensitivity	1.000000e-07
GCST003802_7	Response to citalopram or escitalopram in depression	6.000000e-07
GCST005094_3	Iris color (L* coordinate)	7.000000e-06
GCST008163_609	Height	9.000000e-06
GCST009245_1	Glaucoma (primary open-angle)	4.000000e-13
GCST90026414_7	Severe insulin-resistant type 2 diabetes	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003949	eye color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	6
Valproic Acid	affects cotreatment, increases expression, affects expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	increases methylation, affects expression, affects cotreatment, affects methylation	2
sodium arsenite	decreases expression	2
potassium chromate(VI)	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
geraniol	increases expression	1
trichostatin A	increases expression	1
arsenite	decreases reaction, affects binding	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
resorcinol	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1

Clinical trials (associated diseases)

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