TRIAP1

Summary

TRIAP1 (TP53 regulated inhibitor of apoptosis 1, HGNC:26937) is a protein-coding gene on chromosome 12q24.31, encoding TP53-regulated inhibitor of apoptosis 1 (O43715). Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. It is a common-essential gene (DepMap: required in 96.7% of cancer cell lines).

Enables p53 binding activity. Contributes to phosphatidic acid transfer activity. Involved in several processes, including DNA damage response, signal transduction by p53 class mediator; negative regulation of apoptotic signaling pathway; and positive regulation of phospholipid transport. Located in mitochondrial intermembrane space and nucleoplasm. Part of protein-containing complex.

Source: NCBI Gene 51499 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 4 total
• Cancer dependency (DepMap): dependent in 96.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_016399

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26937
Approved symbol	TRIAP1
Name	TP53 regulated inhibitor of apoptosis 1
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	P53CSV, WF-1, HSPC132, p53CSV, MDM35
Ensembl gene	ENSG00000170855
Ensembl biotype	protein_coding
OMIM	614943
Entrez	51499

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000302432, ENST00000546954, ENST00000932578

RefSeq mRNA: 1 — MANE Select: NM_016399 NM_016399

CCDS: CCDS9198

Canonical transcript exons

ENST00000546954 — 2 exons

Exon	Start	End
ENSE00001128640	120446226	120446384
ENSE00002373736	120443964	120444955

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 95.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7911 / max 332.3969, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133660	19.3264	1802
133659	1.4647	831

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	95.71	gold quality
tongue squamous epithelium	UBERON:0006919	95.10	gold quality
triceps brachii	UBERON:0001509	94.87	gold quality
deltoid	UBERON:0001476	94.76	gold quality
biceps brachii	UBERON:0001507	94.57	gold quality
gluteal muscle	UBERON:0002000	94.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.33	gold quality
gingival epithelium	UBERON:0001949	94.22	gold quality
body of pancreas	UBERON:0001150	94.09	gold quality
esophagus squamous epithelium	UBERON:0006920	93.75	gold quality
tibialis anterior	UBERON:0001385	93.49	gold quality
squamous epithelium	UBERON:0006914	93.42	gold quality
gingiva	UBERON:0001828	93.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.31	gold quality
amniotic fluid	UBERON:0000173	93.27	gold quality
gastrocnemius	UBERON:0001388	93.20	gold quality
muscle of leg	UBERON:0001383	93.14	gold quality
epithelium of esophagus	UBERON:0001976	93.12	gold quality
muscle organ	UBERON:0001630	92.93	gold quality
islet of Langerhans	UBERON:0000006	92.92	gold quality
pancreas	UBERON:0001264	92.91	gold quality
hair follicle	UBERON:0002073	92.52	gold quality
skeletal muscle tissue	UBERON:0001134	92.47	gold quality
oviduct epithelium	UBERON:0004804	92.32	gold quality
diaphragm	UBERON:0001103	92.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.13	gold quality
type B pancreatic cell	CL:0000169	91.97	silver quality
quadriceps femoris	UBERON:0001377	91.95	gold quality
right lobe of liver	UBERON:0001114	91.92	gold quality
vastus lateralis	UBERON:0001379	91.87	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	8.17
E-ANND-3	yes	5.91
E-MTAB-6911	no	525.06
E-MTAB-10290	no	122.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

72 targeting TRIAP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-1255A	99.74	68.09	744

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• HSPC132 is p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway (PMID:15735003)
• Under specific conditions of stress, p53 regulates transcription of p53CSV and that p53CSV is one of the important players in the p53-mediated cell survival. (PMID:15735003)
• Upregulated in at least 50% of multiple myeloma cases tested. (PMID:19171422)
• TRIAP1 is Conserved Specific Coregulators of the p21:PUMA Expression Ratio. (PMID:23684607)
• Loss of TRIAP1 or PRELI impairs the accumulation of Cardiolipin, facilitates the release of cytochrome c, and renders cells vulnerable to apoptosis upon intrinsic and extrinsic stimulation. (PMID:23931759)
• Results describe the upregulation of TRIAP1 in drugresistant breast cancer cells. Its experimental modulation changed breast tumor cells sensitivity to doxorubicin, thus confirming its role in drug resistance. (PMID:25998939)
• crystal structures of free TRIAP1 and TRIAP1-SLMO1 complex reveal how the PRELI domain is chaperoned during import into the intermembrane mitochondrial space; structural resemblance of PRELI-like domain of SLMO1 with that of mammalian phoshatidylinositol transfer proteins suggest they share similar lipid transfer mechanisms (PMID:26071602)
• Inhibition of TRIAP1 in RPMI8226 cells increased the percentage of apoptotic cells, accompanied by increased expression of APAF1 and Caspase 9, and Caspase 9 and Caspase 3/7 activity. (PMID:27032384)
• TRIAP1 is regulated by miR-320b and has a role in progression in nasopharyngeal carcinoma (PMID:27428374)
• miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1. (PMID:31433581)
• TRIAP1 knockdown sensitizes non-small cell lung cancer to ionizing radiation by disrupting redox homeostasis. (PMID:32096592)
• Regulation of Apoptosis and Inflammatory Response in Interleukin-1beta-Induced Nucleus Pulposus Cells by miR-125b-5p Via Targeting TRIAP1. (PMID:33123835)
• Circular RNA circPVT1 Contributes to Doxorubicin (DXR) Resistance of Osteosarcoma Cells by Regulating TRIAP1 via miR-137. (PMID:33981772)
• Triap1 upregulation promotes escape from mitotic-slippage-induced G1 arrest. (PMID:36917609)
• Circular RNA NFIX Functions as an Oncogene in Non-Small Cell Lung Cancer by Modulating the miR-214-3p/TRIAP1 Axis. (PMID:39135128)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Triap1	ENSMUSG00000029535
rattus_norvegicus	Triap1	ENSRNOG00000001160

Protein

Protein identifiers

TP53-regulated inhibitor of apoptosis 1 — O43715 (reviewed: O43715)

Alternative names: Protein 15E1.1, WF-1, p53-inducible cell-survival factor

All UniProt accessions (1): O43715

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Likewise, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis.

Subunit / interactions. Monomer. Interacts with APAF1 and HSP70. Forms a complex with PRELID1 in the mitochondrion intermembrane space. Interacts with PRELID3A.

Subcellular location. Mitochondrion. Mitochondrion intermembrane space.

Induction. In p53/TP53-dependent manner in response to low levels of DNA damage. Not induced when DNA damage is severe.

Similarity. Belongs to the TRIAP1/MDM35 family.

RefSeq proteins (1): NP_057483* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007918	MDM35_apoptosis	Family

Pfam: PF05254

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phosphate(in) = a 1,2-diacyl-sn-glycero-3-phosphate(out) (RHEA:36435)

UniProt features (17 total): helix 5, short sequence motif 2, site 2, disulfide bond 2, chain 1, domain 1, mutagenesis site 1, strand 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6I3V	X-RAY DIFFRACTION	1.98
4XZS	X-RAY DIFFRACTION	2.12
8AG0	X-RAY DIFFRACTION	2.7
6I4Y	X-RAY DIFFRACTION	2.91
6I3Y	X-RAY DIFFRACTION	2.98
4XZV	X-RAY DIFFRACTION	3.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43715-F1	88.23	0.72

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 (2): 27 (important for interaction with prelid3a); 41 (important for interaction with prelid3a)

Post-translational modifications (1): 1

Disulfide bonds (2): 8–47, 18–37

Mutagenesis-validated functional residues (1):

Position	Phenotype
27	impairs interaction with prelid3a.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-9837999	Mitochondrial protein degradation

MSigDB gene sets: 288 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_CELL_CYCLE_PHASE_TRANSITION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT

GO Biological Process (14): apoptotic process (GO:0006915), phospholipid transport (GO:0015914), DNA damage response, signal transduction by p53 class mediator (GO:0030330), mitotic G1 DNA damage checkpoint signaling (GO:0031571), cellular response to UV (GO:0034644), negative regulation of apoptotic process (GO:0043066), phospholipid translocation (GO:0045332), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of release of cytochrome c from mitochondria (GO:0090201), regulation of membrane lipid distribution (GO:0097035), intermembrane lipid transfer (GO:0120009), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902166), positive regulation of phospholipid transport (GO:2001140), lipid transport (GO:0006869)

GO Molecular Function (3): p53 binding (GO:0002039), protein binding (GO:0005515), phosphatidic acid transfer activity (GO:1990050)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid transport	2
phospholipid transport	2
membrane organization	2
intracellular membrane-bounded organelle	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
organophosphate ester transport	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
mitotic G1 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G1/S transition checkpoint signaling	1
response to UV	1
cellular response to light stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
lipid translocation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
release of cytochrome c from mitochondria	1
negative regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
negative regulation of apoptotic signaling pathway	1
regulation of biological quality	1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
positive regulation of lipid transport	1
regulation of phospholipid transport	1
transport	1
lipid localization	1
protein binding	1
binding	1
phospholipid transfer activity	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIAP1	PRELID1	Q9Y255	969
TRIAP1	PRELID3B	Q9Y3B1	913
TRIAP1	TAMM41	Q96BW9	689
TRIAP1	PRELID3A	Q96N28	624
TRIAP1	PRELID2	Q8N945	620
TRIAP1	ATP23	Q9Y6H3	605
TRIAP1	STARD7	Q9NQZ5	557
TRIAP1	CHCHD4	Q8N4Q1	512
TRIAP1	HSPA4	P34932	479
TRIAP1	SESN1	Q9Y6P5	479
TRIAP1	TP53I3	Q53FA7	455
TRIAP1	PISD	Q9UG56	455
TRIAP1	PIDD1	Q9HB75	444
TRIAP1	DRAM1	Q8N682	418
TRIAP1	COX17	Q14061	384

IntAct

35 interactions, top by confidence:

A	B	Type	Score
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
PRELID3B	TRIAP1	psi-mi:“MI:0914”(association)	0.710
TRIAP1	PRELID3B	psi-mi:“MI:0915”(physical association)	0.710
TRIAP1	LCN2	psi-mi:“MI:0915”(physical association)	0.560
TRIAP1	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
TRIAP1	JCHAIN	psi-mi:“MI:0914”(association)	0.530
PRELID3A	TRIAP1	psi-mi:“MI:0914”(association)	0.530
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420
AMY2A	TRIAP1	psi-mi:“MI:0915”(physical association)	0.370
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
ALDH16A1	TRIAP1	psi-mi:“MI:0914”(association)	0.350
AIFM1	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
COX14	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
COX4I1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
PLGRKT	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SCO1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SFXN1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
IMMP1L	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
PARL	HAX1	psi-mi:“MI:2364”(proximity)	0.270
TRIAP1	LCN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (69): TRIAP1 (Affinity Capture-MS), TRIAP1 (Co-fractionation), TRIAP1 (Co-fractionation), TRIAP1 (Co-fractionation), TRIAP1 (Affinity Capture-MS), TRIAP1 (Affinity Capture-MS), TRIAP1 (Affinity Capture-MS), PRELID1 (Affinity Capture-MS), SLMO2 (Affinity Capture-MS), SLMO1 (Affinity Capture-MS), IGJ (Affinity Capture-MS), TRIAP1 (Co-crystal Structure), TRIAP1 (Co-crystal Structure), TRIAP1 (Proximity Label-MS), TRIAP1 (Proximity Label-MS)

ESM2 similar proteins: A1L3N6, A6ZMQ6, A9ULB4, B3LM82, B5FXK1, C8ZF59, O42921, O43715, O43920, O60200, O94581, P00429, P0CB87, P0CB88, P0CT19, P14854, P48504, P56277, P56391, Q01519, Q02379, Q0MQH3, Q0MQH4, Q0P451, Q208S3, Q28BU7, Q28CA1, Q2NKR3, Q3E7A9, Q3ZCK8, Q4R374, Q4R3M6, Q53CG4, Q5RCT0, Q5RFJ0, Q6DD38, Q6DHJ6, Q6INR6, Q6YFQ2, Q7S4H6

Diamond homologs: A9ULB4, O43715, O60200, Q6DD38, Q6INR6, Q96VG1, Q9D8Z2, Q9SMZ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

386 predictions. Top by Δscore:

Variant	Effect	Δscore
12:120446222:TCA:T	donor_loss	1.0000
12:120446223:CACC:C	donor_loss	1.0000
12:120444952:CTTT:C	acceptor_gain	0.9900
12:120444956:C:CC	acceptor_gain	0.9900
12:120444959:G:GC	acceptor_gain	0.9900
12:120446220:GCTCA:G	donor_loss	0.9900
12:120446224:A:AC	donor_gain	0.9900
12:120446225:C:CC	donor_gain	0.9900
12:120444953:TTT:T	acceptor_gain	0.9800
12:120444956:CTG:C	acceptor_loss	0.9800
12:120444957:T:A	acceptor_loss	0.9800
12:120444959:G:C	acceptor_gain	0.9800
12:120445641:A:AC	donor_gain	0.9700
12:120444954:TT:T	acceptor_gain	0.9600
12:120444872:TC:T	donor_gain	0.9500
12:120445642:T:C	donor_gain	0.9500
12:120446235:CTG:C	donor_gain	0.9500
12:120446234:A:AC	donor_gain	0.9300
12:120446235:C:CC	donor_gain	0.9300
12:120445737:C:CC	acceptor_gain	0.9100
12:120446135:A:AG	acceptor_gain	0.9100
12:120446136:G:GG	acceptor_gain	0.9100
12:120444766:C:CG	donor_gain	0.8900
12:120445600:C:CT	donor_gain	0.8800
12:120445601:T:TT	donor_gain	0.8800
12:120444747:G:GT	donor_gain	0.8600
12:120444947:TATTG:T	acceptor_gain	0.8600
12:120444863:C:G	donor_gain	0.8500
12:120444953:T:C	acceptor_gain	0.8500
12:120445637:A:C	donor_gain	0.8500

AlphaMissense

516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:120446230:A:T	V48D	1.000
12:120446233:C:G	C47S	1.000
12:120446234:A:G	C47R	1.000
12:120446234:A:T	C47S	1.000
12:120446262:G:C	C37W	1.000
12:120446263:C:T	C37Y	1.000
12:120446304:G:C	F23L	1.000
12:120446304:G:T	F23L	1.000
12:120446305:A:G	F23S	1.000
12:120446306:A:G	F23L	1.000
12:120446307:C:A	W22C	1.000
12:120446307:C:G	W22C	1.000
12:120446309:A:G	W22R	1.000
12:120446309:A:T	W22R	1.000
12:120446316:G:C	F19L	1.000
12:120446316:G:T	F19L	1.000
12:120446318:A:G	F19L	1.000
12:120446321:A:G	C18R	1.000
12:120446329:T:C	Y15C	1.000
12:120446337:C:A	K12N	1.000
12:120446337:C:G	K12N	1.000
12:120446349:G:C	C8W	1.000
12:120446350:C:T	C8Y	1.000
12:120446351:A:G	C8R	1.000
12:120444933:A:G	I57T	0.999
12:120444952:C:G	A51P	0.999
12:120446232:A:C	C47W	0.999
12:120446233:C:A	C47F	0.999
12:120446233:C:T	C47Y	0.999
12:120446242:T:C	Y44C	0.999

dbSNP variants (sampled 300 via entrez): RS1000760678 (12:120447486 C>A,T), RS1000818702 (12:120447203 G>A), RS1000838329 (12:120446384 T>C,G), RS1001414997 (12:120444793 A>C,G), RS1001487967 (12:120444440 A>G), RS1002248402 (12:120447878 C>G,T), RS1002419164 (12:120446347 G>A,T), RS1003855022 (12:120447085 T>G), RS1003941678 (12:120446538 T>A,G), RS1004974300 (12:120447564 G>C), RS1006020179 (12:120443982 A>G), RS1006382316 (12:120443575 T>G), RS1006486797 (12:120444344 GCCA>G), RS1006977951 (12:120445073 T>C), RS1007441346 (12:120445381 A>G)

Disease associations

OMIM: gene MIM:614943 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001208_11	Insulin resistance/response	1.000000e-06
GCST004401_6	Reading disability or specific language impairment (pleiotropy)	4.000000e-06
GCST004402_1	Reading disability or specific language impairment adjusted for intelligence quotient (pleiotropy)	1.000000e-06
GCST90002387_127	Immature fraction of reticulocytes	3.000000e-26

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression	5
Benzo(a)pyrene	increases expression	4
Cisplatin	increases expression	4
Leflunomide	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
dicrotophos	decreases expression	1
tungsten carbide	affects cotreatment, increases expression	1
chloroacetaldehyde	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium bromate	increases expression	1
ochratoxin A	decreases expression	1
3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz(a)anthracene	increases expression	1
periodate-oxidized adenosine	affects expression	1
polyhexamethyleneguanidine	increases expression	1
buprofezin	decreases expression	1
adefovir dipivoxil	increases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
jinfukang	decreases expression	1
Cidofovir	increases expression	1
Acetaminophen	increases expression	1
Adenine	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Cobalt	affects cotreatment, increases expression	1
Colchicine	decreases expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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