P4HA3

Summary

P4HA3 (prolyl 4-hydroxylase subunit alpha 3, HGNC:30135) is a protein-coding gene on chromosome 11q13.4, encoding Prolyl 4-hydroxylase subunit alpha-3 (Q7Z4N8). Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.

This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 283208 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_182904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30135
Approved symbol	P4HA3
Name	prolyl 4-hydroxylase subunit alpha 3
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	C-P4Halpha(III)
Ensembl gene	ENSG00000149380
Ensembl biotype	protein_coding
OMIM	608987
Entrez	283208

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000331597, ENST00000427714, ENST00000524388, ENST00000525968, ENST00000531716, ENST00000532689, ENST00000540363, ENST00000871234, ENST00000871235, ENST00000953680

RefSeq mRNA: 2 — MANE Select: NM_182904 NM_001288748, NM_182904

CCDS: CCDS73347, CCDS8230

Canonical transcript exons

ENST00000331597 — 13 exons

Exon	Start	End
ENSE00001306196	74304270	74304412
ENSE00002183632	74266657	74267318
ENSE00002200593	74311412	74311640
ENSE00003458993	74298212	74298361
ENSE00003480322	74268145	74268241
ENSE00003491274	74285809	74285985
ENSE00003513351	74269652	74269720
ENSE00003558265	74302369	74302592
ENSE00003577341	74279388	74279452
ENSE00003577917	74273545	74273607
ENSE00003620097	74286228	74286391
ENSE00003634572	74276985	74277144
ENSE00003693949	74289079	74289130

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 95.56.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8827 / max 162.9747, expressed in 677 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121311	2.8827	677

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	95.56	gold quality
stromal cell of endometrium	CL:0002255	94.04	gold quality
left ventricle myocardium	UBERON:0006566	84.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	84.85	gold quality
kidney epithelium	UBERON:0004819	82.52	gold quality
upper arm skin	UBERON:0004263	81.63	gold quality
tibia	UBERON:0000979	81.53	gold quality
right coronary artery	UBERON:0001625	80.44	gold quality
buccal mucosa cell	CL:0002336	80.36	gold quality
tendon of biceps brachii	UBERON:0008188	79.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.77	gold quality
calcaneal tendon	UBERON:0003701	79.77	gold quality
smooth muscle tissue	UBERON:0001135	79.75	gold quality
cartilage tissue	UBERON:0002418	79.55	gold quality
islet of Langerhans	UBERON:0000006	79.25	gold quality
gall bladder	UBERON:0002110	78.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.49	gold quality
tendon	UBERON:0000043	77.76	gold quality
coronary artery	UBERON:0001621	77.75	gold quality
left coronary artery	UBERON:0001626	77.60	gold quality
urethra	UBERON:0000057	76.98	gold quality
nasal cavity epithelium	UBERON:0005384	76.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.71	gold quality
myometrium	UBERON:0001296	76.54	gold quality
myocardium	UBERON:0002349	76.06	gold quality
vermiform appendix	UBERON:0001154	74.98	gold quality
pericardium	UBERON:0002407	74.53	silver quality
adenohypophysis	UBERON:0002196	74.40	gold quality
caecum	UBERON:0001153	73.90	gold quality
layer of synovial tissue	UBERON:0007616	73.83	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting P4HA3, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-132-5P	96.61	65.79	115

Literature-anchored findings (GeneRIF, showing 9)

• analysis of collagen prolyl 4-hydroxylase isoenzyme 3, its expression and catalytic properties (PMID:14500733)
• HIF-P4H, HIF-1alpha and HIF-2alpha are effective oxygen sensors (PMID:16885164)
• Based on findings above, we infer that P4HA3 is epigenetically activated by Slug, and its deregulation is associated with enhanced metastasis and poor survival of gastric cancer. (PMID:30198421)
• Prolyl 4-hydroxylase subunit alpha 3 presents a cancer promotive function in head and neck squamous cell carcinoma via regulating epithelial-mesenchymal transition. (PMID:32220804)
• Age-associated genes in human mammary gland drive human breast cancer progression. (PMID:32539762)
• Prognostic and diagnostic roles of prolyl 4-hydroxylase subunit alpha members in breast cancer. (PMID:34387118)
• Prolyl 4-hydroxylase subunit alpha 3 facilitates human colon cancer growth and metastasis through the TGF-beta/Smad signaling pathway. (PMID:34959098)
• miR-1266-3p Suppresses Epithelial-Mesenchymal Transition in Colon Cancer by Targeting P4HA3. (PMID:35433237)
• P4HA3 promotes clear cell renal cell carcinoma progression via the PI3K/AKT/GSK3beta pathway. (PMID:36588128)

Cross-species orthologs

34 orthologs

Organism	Symbol	Gene ID
danio_rerio	p4ha3	ENSDARG00000103692
danio_rerio	si:cabz01069582.1	ENSDARG00000105349
mus_musculus	P4ha3	ENSMUSG00000051048
rattus_norvegicus	P4ha3	ENSRNOG00000017118
drosophila_melanogaster	PH4alphaMP	FBGN0026190
drosophila_melanogaster	CG4174	FBGN0036793
drosophila_melanogaster	CG18233	FBGN0036795
drosophila_melanogaster	CG18231	FBGN0036796
drosophila_melanogaster	CG11828	FBGN0039616
drosophila_melanogaster	PH4alphaEFB	FBGN0039776
drosophila_melanogaster	PH4alphaSG2	FBGN0039779
drosophila_melanogaster	PH4alphaNE1	FBGN0039780
drosophila_melanogaster	CG15539	FBGN0039782
drosophila_melanogaster	PH4alphaNE2	FBGN0039783
drosophila_melanogaster	CG9698	FBGN0039784
drosophila_melanogaster	CG15864	FBGN0040528
drosophila_melanogaster	CG18749	FBGN0042182
drosophila_melanogaster	CG31013	FBGN0051013
drosophila_melanogaster	PH4alphaSG1	FBGN0051014
drosophila_melanogaster	PH4alphaPV	FBGN0051015
drosophila_melanogaster	CG31016	FBGN0051016
drosophila_melanogaster	PH4alphaNE3	FBGN0051017
drosophila_melanogaster	CG31021	FBGN0051021
drosophila_melanogaster	CG31371	FBGN0051371
drosophila_melanogaster	CG31524	FBGN0051524
drosophila_melanogaster	CG32199	FBGN0052199
drosophila_melanogaster	CG32201	FBGN0052201
drosophila_melanogaster	CG34041	FBGN0054041
drosophila_melanogaster	CG34345	FBGN0085374
drosophila_melanogaster	CG18234	FBGN0265268
caenorhabditis_elegans		WBGENE00004025
caenorhabditis_elegans		WBGENE00004026
caenorhabditis_elegans		WBGENE00015773
caenorhabditis_elegans		WBGENE00077688

Paralogs (3): P4HA2 (ENSG00000072682), P4HA1 (ENSG00000122884), P4HTM (ENSG00000178467)

Protein

Protein identifiers

Prolyl 4-hydroxylase subunit alpha-3 — Q7Z4N8 (reviewed: Q7Z4N8)

Alternative names: Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-3

All UniProt accessions (3): Q7Z4N8, E9PM97, H0YCC3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.

Subunit / interactions. Heterotetramer of two alpha-3 chains and two beta chains (the beta chain is the multi-functional PDI).

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Highly expressed in placenta, liver and fetal skin. Weakly expressed in fetal epiphyseal cartilage, fetal liver, fibroblast, lung and skeletal muscle. Expressed also in fibrous cap of carotid atherosclerotic lesions.

Post-translational modifications. N-glycosylation plays no role in the catalytic activity.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Similarity. Belongs to the P4HA family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z4N8-1	1	yes
Q7Z4N8-2	2
Q7Z4N8-3	3

RefSeq proteins (2): NP_001275677, NP_878907* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR006620	Pro_4_hyd_alph	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013547	P4H_N	Domain
IPR044862	Pro_4_hyd_alph_FE2OG_OXY	Domain
IPR045054	P4HA-like	Family
IPR059068	TPR_P4H	Domain

Pfam: PF08336, PF13640, PF23558

Enzyme classification (BRENDA):

• EC 1.14.11.2 — procollagen-proline 4-dioxygenase (BRENDA: 37 organisms, 182 substrates, 264 inhibitors, 251 Km, 44 kcat entries)

Substrate kinetics (BRENDA)

77 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.001–1	37
POLY(L-PROLINE)	0.0002–1.59	26
(L-PRO-L-PRO-GLY)10	0.015–2.9	15
(PRO-PRO-GLY)10	0.011–1.27	15
POLY(L-PRO)	0.002–0.65	15
FE2+	0.0004–0.016	9
O2	0.03–1.5	9
ASCORBATE	0.14–0.37	8
(L-PRO-L-PRO-GLY)5	0.12–1.8	6
PROTOCOLLAGEN	—	6
(L-PRO-L-ALA-L-PRO-L-LYS)3	0.09–0.31	4
(SER-PRO)5	0.14–0.78	4
DLDLEMLAPYIPMDD	0.009–0.1	3
DLDLEMLAPYIPMDDDF	0.007–0.07	3
EMLAPYIPMDDDFQL	0.007–0.08	3

Catalyzed reactions (Rhea), 1 shown:

• L-prolyl-[collagen] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl-[collagen] + succinate + CO2 (RHEA:18945)

UniProt features (16 total): binding site 4, splice variant 3, glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, repeat 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4N8-F1	89.00	0.74

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 (4): 440; 442; 510; 520

Glycosylation sites (2): 482, 242

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-9918432	Maturation of DENV proteins

MSigDB gene sets: 70 (showing top): GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, chr11q13, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, MARSON_BOUND_BY_FOXP3_STIMULATED, GOMF_L_ASCORBIC_ACID_BINDING, GOMF_DIOXYGENASE_ACTIVITY, GOMF_ORGANIC_ACID_BINDING, GOMF_VITAMIN_BINDING, GOMF_IRON_ION_BINDING, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, KEGG_ARGININE_AND_PROLINE_METABOLISM, GOMF_PROCOLLAGEN_PROLINE_4_DIOXYGENASE_ACTIVITY, GOMF_PROCOLLAGEN_PROLINE_DIOXYGENASE_ACTIVITY

GO Biological Process (1): collagen fibril organization (GO:0030199)

GO Molecular Function (8): procollagen-proline 4-dioxygenase activity (GO:0004656), iron ion binding (GO:0005506), L-ascorbic acid binding (GO:0031418), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Collagen formation	1
Dengue Virus Genome Translation and Replication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity	2
extracellular matrix organization	1
procollagen-proline dioxygenase activity	1
peptidyl-proline 4-dioxygenase activity	1
transition metal ion binding	1
vitamin binding	1
carboxylic acid binding	1
monosaccharide binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P4HA3	P4HB	P07237	941
P4HA3	COL1A1	P02452	648
P4HA3	COL6A6	A6NMZ7	612
P4HA3	SERPINH1	P29043	577
P4HA3	P3H1	Q32P28	573
P4HA3	ADAMTS2	O95450	561
P4HA3	ADAMTS4	O75173	526
P4HA3	PLOD1	Q02809	516
P4HA3	BMP1	P13497	492
P4HA3	P3H2	Q8IVL5	484
P4HA3	COL10A1	Q03692	483
P4HA3	P4HA2	O15460	476
P4HA3	P3H4	Q92791	470
P4HA3	FN1	P02751	453
P4HA3	PLOD3	O60568	449

IntAct

166 interactions, top by confidence:

A	B	Type	Score
P4HA3	HGS	psi-mi:“MI:0915”(physical association)	0.720
ZC3H12A	P4HA3	psi-mi:“MI:0915”(physical association)	0.720
HGS	P4HA3	psi-mi:“MI:0915”(physical association)	0.720
P4HA3	ZC3H12A	psi-mi:“MI:0915”(physical association)	0.720
NUTM1	P4HA3	psi-mi:“MI:0915”(physical association)	0.670
P4HA3	MAGEC2	psi-mi:“MI:0915”(physical association)	0.670
P4HA3	NUTM1	psi-mi:“MI:0915”(physical association)	0.670
MAGEC2	P4HA3	psi-mi:“MI:0915”(physical association)	0.670
MAGEA2	P4HA3	psi-mi:“MI:0915”(physical association)	0.670
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
	P4HA3	psi-mi:“MI:0915”(physical association)	0.600
P4HA3		psi-mi:“MI:0915”(physical association)	0.600
P4HA3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
WDR62	P4HA3	psi-mi:“MI:0915”(physical association)	0.560
SERTAD1	P4HA3	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	MAGEA2B	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	DTNBP1	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	WDR62	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (172): P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), P4HA3 (Two-hybrid), WDR62 (Two-hybrid), P4HA3 (Affinity Capture-RNA), ZBTB7B (Affinity Capture-MS), KIF21A (Affinity Capture-MS), ZMYND8 (Affinity Capture-MS), KMT2B (Affinity Capture-MS), ZNF687 (Affinity Capture-MS)

ESM2 similar proteins: A3KGW5, B1WC86, C7G3A0, D2I2M6, O18835, O77588, P06802, P08236, P58242, Q02809, Q04519, Q0IHA5, Q0VD19, Q32NJ7, Q3U4H6, Q4FAT7, Q502B3, Q53F39, Q566Y9, Q5F2L1, Q5F2L2, Q5IGR6, Q5R5N6, Q5R9N3, Q5RET5, Q5U309, Q5VSG8, Q5XPT3, Q5ZK82, Q69ZQ1, Q6P1J0, Q6P7A1, Q6P9A2, Q6PA90, Q6W3E9, Q6W3F0, Q6ZNF0, Q75UG4, Q7Z4N8, Q80XL7

Diamond homologs: F4ILF8, F4J0A8, F4JAU3, F4JNU8, F4JZ24, O15460, P0DUB0, P13674, P16924, P54001, Q10576, Q19673, Q1RMU3, Q20065, Q24JN5, Q5RAG8, Q5UP57, Q5ZLK5, Q60715, Q60716, Q6W3E9, Q6W3F0, Q75UG4, Q7Z4N8, Q8BG58, Q8GXT7, Q8L970, Q8LAN3, Q8VZJ7, Q9LN20, Q9NXG6, Q9SZT0, Q9ZW86

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3305 predictions. Top by Δscore:

Variant	Effect	Δscore
11:74235899:A:AG	acceptor_gain	1.0000
11:74235900:G:GG	acceptor_gain	1.0000
11:74235967:G:GG	donor_gain	1.0000
11:74239242:G:GT	donor_gain	1.0000
11:74247075:CTAG:C	acceptor_loss	1.0000
11:74247077:A:AG	acceptor_gain	1.0000
11:74247077:A:AT	acceptor_loss	1.0000
11:74247078:G:GG	acceptor_gain	1.0000
11:74247122:AGGTA:A	donor_loss	1.0000
11:74247124:G:GG	donor_gain	1.0000
11:74253490:A:AG	acceptor_gain	1.0000
11:74253491:G:GG	acceptor_gain	1.0000
11:74253491:GT:G	acceptor_gain	1.0000
11:74253491:GTGT:G	acceptor_gain	1.0000
11:74267317:CA:C	acceptor_gain	1.0000
11:74267319:C:CC	acceptor_gain	1.0000
11:74268144:CCCCA:C	donor_gain	1.0000
11:74268153:T:C	donor_gain	1.0000
11:74269718:CAG:C	acceptor_gain	1.0000
11:74273543:A:AC	donor_gain	1.0000
11:74273544:C:CC	donor_gain	1.0000
11:74273544:CATAG:C	donor_gain	1.0000
11:74273605:TGA:T	acceptor_gain	1.0000
11:74273606:GA:G	acceptor_gain	1.0000
11:74273608:C:CC	acceptor_gain	1.0000
11:74277143:CA:C	acceptor_gain	1.0000
11:74277145:C:CC	acceptor_gain	1.0000
11:74284202:T:TA	donor_gain	1.0000
11:74285801:ACACT:A	donor_loss	1.0000
11:74285802:CACT:C	donor_loss	1.0000

AlphaMissense

3509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:74267305:C:A	W526C	0.999
11:74267305:C:G	W526C	0.999
11:74267307:A:G	W526R	0.999
11:74267307:A:T	W526R	0.999
11:74268181:G:C	H510D	0.999
11:74276995:T:A	D442V	0.999
11:74277002:G:C	H440D	0.999
11:74277138:C:A	W394C	0.999
11:74277138:C:G	W394C	0.999
11:74279393:G:C	S390R	0.999
11:74279393:G:T	S390R	0.999
11:74279395:T:G	S390R	0.999
11:74286247:C:G	C305S	0.999
11:74286248:A:T	C305S	0.999
11:74267316:C:G	A523P	0.998
11:74268149:C:A	K520N	0.998
11:74268149:C:G	K520N	0.998
11:74268165:A:T	V515D	0.998
11:74268170:A:C	C513W	0.998
11:74268171:C:G	C513S	0.998
11:74268171:C:T	C513Y	0.998
11:74268172:A:G	C513R	0.998
11:74268172:A:T	C513S	0.998
11:74268181:G:T	H510N	0.998
11:74268218:G:C	N497K	0.998
11:74268218:G:T	N497K	0.998
11:74268226:A:G	W495R	0.998
11:74268226:A:T	W495R	0.998
11:74273568:G:C	R459G	0.998
11:74276994:G:C	D442E	0.998

dbSNP variants (sampled 300 via entrez): RS1000007787 (11:74260391 C>G,T), RS1000013050 (11:74277387 G>A,C), RS1000125678 (11:74253859 A>G), RS1000173339 (11:74282235 G>C), RS1000212695 (11:74271629 G>A), RS1000287210 (11:74306770 C>A), RS1000287799 (11:74294585 C>A,G,T), RS1000301720 (11:74312947 A>G), RS1000355186 (11:74312655 A>G), RS1000379150 (11:74293883 T>C), RS1000383927 (11:74293586 A>C,G), RS1000471551 (11:74271854 G>C), RS1000476113 (11:74281069 G>A,T), RS1000527625 (11:74259094 G>C), RS1000530091 (11:74305875 C>T)

Disease associations

OMIM: gene MIM:608987 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002760_2	Hippocampal atrophy	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
abrine	increases expression	1
jinfukang	increases expression, affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1

Clinical trials (associated diseases)

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