GTF2H3

Summary

GTF2H3 (general transcription factor IIH subunit 3, HGNC:4657) is a protein-coding gene on chromosome 12q24.31, encoding General transcription factor IIH subunit 3 (Q13889). Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. It is a selective cancer dependency (DepMap: 84.4% of cell lines).

This gene encodes a member of the TFB4 family. The encoded protein is a subunit of the core-TFIIH basal transcription factor and localizes to the nucleus. The encoded protein is involved in RNA transcription by RNA polymerase II and nucleotide excision repair and associates with the Cdk-activating kinase complex. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 14.

Source: NCBI Gene 2967 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 45 total
• Cancer dependency (DepMap): dependent in 84.4% of screened cell lines
• MANE Select transcript: NM_001516

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4657
Approved symbol	GTF2H3
Name	general transcription factor IIH subunit 3
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	BTF2, TFIIH, P34
Ensembl gene	ENSG00000111358
Ensembl biotype	protein_coding
OMIM	601750
Entrez	2967

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000228955, ENST00000536375, ENST00000537368, ENST00000537695, ENST00000538533, ENST00000538845, ENST00000539429, ENST00000539994, ENST00000542279, ENST00000543005, ENST00000543154, ENST00000543341, ENST00000543415, ENST00000618160

RefSeq mRNA: 4 — MANE Select: NM_001516 NM_001271866, NM_001271867, NM_001271868, NM_001516

CCDS: CCDS61275, CCDS73544, CCDS9252

Canonical transcript exons

ENST00000543341 — 13 exons

Exon	Start	End
ENSE00002262553	123660166	123662604
ENSE00003487033	123652532	123652561
ENSE00003488959	123655771	123655824
ENSE00003497879	123645455	123645561
ENSE00003501644	123652707	123652735
ENSE00003503298	123660046	123660082
ENSE00003525008	123659516	123659584
ENSE00003577706	123639264	123639343
ENSE00003581097	123650994	123651056
ENSE00003591500	123647963	123648126
ENSE00003636716	123659795	123659930
ENSE00003685037	123633829	123633872
ENSE00003785505	123654924	123654998

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.4415 / max 598.3145, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128593	26.9528	1806
128592	3.7704	1553
128591	0.7183	395

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.70	silver quality
endothelial cell	CL:0000115	98.57	gold quality
cervix squamous epithelium	UBERON:0006922	98.34	silver quality
male germ cell	CL:0000015	98.23	silver quality
cardia of stomach	UBERON:0001162	97.99	gold quality
nipple	UBERON:0002030	97.95	gold quality
renal medulla	UBERON:0000362	97.82	gold quality
ventral tegmental area	UBERON:0002691	97.79	gold quality
pylorus	UBERON:0001166	97.58	gold quality
inferior vagus X ganglion	UBERON:0005363	97.50	gold quality
superior vestibular nucleus	UBERON:0007227	97.47	gold quality
superior surface of tongue	UBERON:0007371	97.42	gold quality
trigeminal ganglion	UBERON:0001675	97.32	gold quality
subthalamic nucleus	UBERON:0001906	97.27	gold quality
buccal mucosa cell	CL:0002336	97.26	gold quality
superficial temporal artery	UBERON:0001614	97.08	gold quality
pharyngeal mucosa	UBERON:0000355	97.06	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.95	gold quality
pericardium	UBERON:0002407	96.84	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.81	gold quality
medulla oblongata	UBERON:0001896	96.70	gold quality
lateral globus pallidus	UBERON:0002476	96.65	gold quality
pons	UBERON:0000988	96.45	gold quality
blood vessel layer	UBERON:0004797	96.36	gold quality
saphenous vein	UBERON:0007318	96.32	gold quality
tongue	UBERON:0001723	96.29	gold quality
vena cava	UBERON:0004087	96.26	silver quality
substantia nigra pars compacta	UBERON:0001965	96.25	gold quality
periodontal ligament	UBERON:0008266	96.23	gold quality
body of tongue	UBERON:0011876	96.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting GTF2H3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AA	99.96	70.64	3753

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• interface variants between the p34 and p44 subunits only mildly affected the association between the full length proteins and did not impinge on TFIIH activities due to the presence of an additional interface involving the C4 domain of p34. (PMID:28977422)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2h3	ENSDARG00000067560
mus_musculus	Gtf2h3	ENSMUSG00000029387
rattus_norvegicus	Gtf2h3	ENSRNOG00000001035
drosophila_melanogaster	Tfb4	FBGN0031309
caenorhabditis_elegans		WBGENE00014230

Protein

Protein identifiers

General transcription factor IIH subunit 3 — Q13889 (reviewed: Q13889)

Alternative names: Basic transcription factor 2 34 kDa subunit, General transcription factor IIH polypeptide 3, TFIIH basal transcription factor complex p34 subunit

All UniProt accessions (9): A0A087WYD5, Q13889, F5GWD3, F5GX35, F5GXG6, F5H3G1, F5H4K7, F5H6X0, H0YFF7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.

Subunit / interactions. Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with RARA; the interaction requires prior phosphorylation of RARA on ‘Ser-369’ which then enhances interaction of RARA with CDK7.

Subcellular location. Nucleus.

Similarity. Belongs to the TFB4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13889-1	1	yes
Q13889-2	2

RefSeq proteins (4): NP_001258795, NP_001258796, NP_001258797, NP_001507* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004600	TFIIH_Tfb4/GTF2H3	Family
IPR036465	vWFA_dom_sf	Homologous_superfamily

Pfam: PF03850

UniProt features (24 total): helix 11, strand 9, chain 1, zinc finger region 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
28JM	ELECTRON MICROSCOPY	3.29
7EGB	ELECTRON MICROSCOPY	3.3
8EBU	ELECTRON MICROSCOPY	3.3
9PD3	ELECTRON MICROSCOPY	3.3
28JS	ELECTRON MICROSCOPY	3.32
5O85	X-RAY DIFFRACTION	3.4
9PD4	ELECTRON MICROSCOPY	3.4
6RO4	ELECTRON MICROSCOPY	3.5
7AD8	ELECTRON MICROSCOPY	3.5
9XYU	ELECTRON MICROSCOPY	3.5
28KE	ELECTRON MICROSCOPY	3.6
8EBX	ELECTRON MICROSCOPY	3.6
8EBY	ELECTRON MICROSCOPY	3.6
6NMI	ELECTRON MICROSCOPY	3.7
7EGC	ELECTRON MICROSCOPY	3.9
7NVX	ELECTRON MICROSCOPY	3.9
8EBT	ELECTRON MICROSCOPY	3.9
28JV	ELECTRON MICROSCOPY	3.91
8BVW	ELECTRON MICROSCOPY	4
8EBS	ELECTRON MICROSCOPY	4
7ENA	ELECTRON MICROSCOPY	4.07
8BYQ	ELECTRON MICROSCOPY	4.1
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
7NVW	ELECTRON MICROSCOPY	4.3
9PCP	ELECTRON MICROSCOPY	4.3
5OF4	ELECTRON MICROSCOPY	4.4
6O9M	ELECTRON MICROSCOPY	4.4
7NVR	ELECTRON MICROSCOPY	4.5
7LBM	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13889-F1	80.72	0.39

Function

Pathways and Gene Ontology

Reactome pathways

48 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-72086	mRNA Capping
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-77075	RNA Pol II CTD phosphorylation and interaction with CE
R-HSA-162587	HIV Life Cycle

MSigDB gene sets: 182 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, MODULE_16, KAUFFMANN_DNA_REPAIR_GENES, GOBP_NUCLEOTIDE_EXCISION_REPAIR, REACTOME_HIV_INFECTION, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_FANCG, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, MCCABE_HOXC6_TARGETS_CANCER_DN, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, DODD_NASOPHARYNGEAL_CARCINOMA_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP

GO Biological Process (5): DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366), DNA damage response (GO:0006974)

GO Molecular Function (4): zinc ion binding (GO:0008270), RNA polymerase II general transcription initiation factor activity (GO:0016251), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): core TFIIH complex portion of holo TFIIH complex (GO:0000438), transcription factor TFIIH core complex (GO:0000439), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), transcription factor TFIIH holo complex (GO:0005675), transcription preinitiation complex (GO:0097550)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Transcription of the HIV genome	4
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
RNA Polymerase II Transcription Elongation	2
HIV Transcription Elongation	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Negative epigenetic regulation of rRNA expression	1
RNA Polymerase II Transcription	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulator complex	3
DNA-templated transcription	2
transcription factor TFIIH core complex	2
RNA polymerase II, holoenzyme	2
DNA metabolic process	1
DNA damage response	1
DNA repair	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
transition metal ion binding	1
transcription by RNA polymerase II	1
general transcription initiation factor activity	1
binding	1
cation binding	1
transcription factor TFIIH holo complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
carboxy-terminal domain protein kinase complex	1
protein-DNA complex	1

Protein interactions and networks

STRING

1329 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2H3	GTF2H4	Q92759	997
GTF2H3	GTF2H1	P32780	997
GTF2H3	GTF2H2	Q13888	997
GTF2H3	ERCC3	P19447	996
GTF2H3	ERCC2	P18074	995
GTF2H3	GTF2H5	Q6ZYL4	981
GTF2H3	CCNH	P51946	902
GTF2H3	MNAT1	P51948	866
GTF2H3	CDK7	P50613	854
GTF2H3	GTF2H2C	Q6P1K8	797
GTF2H3	RAD23B	P54727	702
GTF2H3	XPA	P23025	664
GTF2H3	ERCC1	P07992	593
GTF2H3	GTF2B	Q00403	477
GTF2H3	ERCC5	P28715	446

IntAct

52 interactions, top by confidence:

A	B	Type	Score
GTF2H1	CDK7	psi-mi:“MI:0915”(physical association)	0.820
GTF2H3	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.800
GTF2H2C	GTF2H3	psi-mi:“MI:0915”(physical association)	0.800
CCNH	ERCC2	psi-mi:“MI:0915”(physical association)	0.750
GTF2H3	GTF2H1	psi-mi:“MI:0914”(association)	0.740
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
ERCC2	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
GTF2H5	ERCC2	psi-mi:“MI:0914”(association)	0.650
GTF2H3	ERCC3	psi-mi:“MI:0914”(association)	0.640
GTF2H3	GTF2H2	psi-mi:“MI:0914”(association)	0.640
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
ERCC3	BCR	psi-mi:“MI:0914”(association)	0.530
GTF2H2C	ERCC3	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
GTF2H3	MANF	psi-mi:“MI:0915”(physical association)	0.400
GTF2H3	RARS1	psi-mi:“MI:0915”(physical association)	0.400
GTF2H3	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
GTF2H3	THRAP3	psi-mi:“MI:0915”(physical association)	0.400
GTF2H3	SMC2	psi-mi:“MI:0915”(physical association)	0.400
GTF2H3	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
CDK7	SEC16A	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GTF2H2C	GTF2H2C	psi-mi:“MI:0914”(association)	0.350
PRDM11	ERCC3	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (114): GTF2H2C_2 (Two-hybrid), GTF2H3 (Affinity Capture-MS), GTF2H3 (Affinity Capture-MS), GTF2H1 (Co-fractionation), GTF2H2C (Co-fractionation), GTF2H2 (Co-fractionation), GTF2H2C_2 (Co-fractionation), GTF2H3 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H3 (Affinity Capture-MS), GTF2H3 (Affinity Capture-MS), GTF2H3 (Affinity Capture-MS), GTF2H5 (Affinity Capture-MS), GTF2H3 (Affinity Capture-MS), GTF2H1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN39, A8WGF4, B0BN93, B4F6Y3, B5G0G8, D2SW95, O54956, O88653, P23514, P53618, P84169, Q05B56, Q0JNK5, Q13889, Q17QQ1, Q28C65, Q3SX43, Q4SSF5, Q503S6, Q53PC7, Q5E964, Q5FVD6, Q5R3Z6, Q5R922, Q5U204, Q5XGS8, Q5ZIA5, Q5ZIP2, Q5ZKR4, Q63486, Q6GNI4, Q6NWV3, Q6PC62, Q6Y228, Q6Z844, Q7L523, Q7T0T2, Q7T0V2, Q80X95, Q84LG4

Diamond homologs: O74366, Q05B56, Q12004, Q13889, Q561R7, Q6BL86, Q6CD24, Q6CVX9, Q6FWA7, Q75B93, Q86IB5, Q8LF41, Q8VD76

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF2H3	“form complex”	TFIIH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	10	104.6×	9e-17
RNA Pol II CTD phosphorylation and interaction with CE	10	104.6×	9e-17
mRNA Capping	10	97.6×	1e-16
Formation of the Early Elongation Complex	10	86.1×	2e-16
Formation of the HIV-1 Early Elongation Complex	10	86.1×	2e-16
Global Genome Nucleotide Excision Repair (GG-NER)	7	82.0×	2e-11
Formation of Incision Complex in GG-NER	12	78.1×	4e-18
RNA Polymerase I Transcription Termination	9	75.3×	2e-14

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	11	91.6×	4e-17
transcription initiation at RNA polymerase II promoter	10	81.4×	4e-15
transcription by RNA polymerase II	9	13.8×	2e-06
DNA repair	7	9.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2078 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123645450:A:AG	acceptor_gain	1.0000
12:123645451:A:G	acceptor_gain	1.0000
12:123645453:A:AG	acceptor_gain	1.0000
12:123645454:G:GA	acceptor_gain	1.0000
12:123645454:GT:G	acceptor_gain	1.0000
12:123645454:GTT:G	acceptor_gain	1.0000
12:123645454:GTTC:G	acceptor_gain	1.0000
12:123645454:GTTCA:G	acceptor_gain	1.0000
12:123645557:GAAAG:G	donor_gain	1.0000
12:123645562:GTAT:G	donor_loss	1.0000
12:123645563:T:G	donor_loss	1.0000
12:123647961:A:AG	acceptor_gain	1.0000
12:123647962:G:GG	acceptor_gain	1.0000
12:123648046:G:GT	donor_gain	1.0000
12:123648087:G:GT	donor_gain	1.0000
12:123648127:G:GG	donor_gain	1.0000
12:123659793:AGTG:A	acceptor_gain	1.0000
12:123659794:GTGG:G	acceptor_gain	1.0000
12:123633946:A:T	donor_gain	0.9900
12:123634019:G:GG	donor_gain	0.9900
12:123639253:A:AG	acceptor_gain	0.9900
12:123639256:A:AG	acceptor_gain	0.9900
12:123639262:A:AG	acceptor_gain	0.9900
12:123639263:G:GG	acceptor_gain	0.9900
12:123639263:GAA:G	acceptor_gain	0.9900
12:123645562:G:GG	donor_gain	0.9900
12:123647955:T:A	acceptor_gain	0.9900
12:123647961:AGCC:A	acceptor_gain	0.9900
12:123647962:GCC:G	acceptor_gain	0.9900
12:123647962:GCCG:G	acceptor_gain	0.9900

AlphaMissense

2032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:123654981:T:C	F182L	1.000
12:123654982:T:G	F182C	1.000
12:123654983:T:A	F182L	1.000
12:123654983:T:G	F182L	1.000
12:123654987:G:C	A184P	1.000
12:123659535:G:A	G212E	1.000
12:123659868:C:A	A253D	1.000
12:123659871:C:A	A254D	1.000
12:123659873:T:A	C255S	1.000
12:123659873:T:C	C255R	1.000
12:123659874:G:A	C255Y	1.000
12:123659874:G:C	C255S	1.000
12:123659874:G:T	C255F	1.000
12:123659875:C:G	C255W	1.000
12:123659876:T:C	F256L	1.000
12:123659878:C:A	F256L	1.000
12:123659878:C:G	F256L	1.000
12:123659879:T:A	C257S	1.000
12:123659879:T:C	C257R	1.000
12:123659880:G:A	C257Y	1.000
12:123659880:G:C	C257S	1.000
12:123659880:G:T	C257F	1.000
12:123659881:T:G	C257W	1.000
12:123659903:G:C	G265R	1.000
12:123659904:G:A	G265D	1.000
12:123659904:G:T	G265V	1.000
12:123659910:T:A	V267D	1.000
12:123659912:T:A	C268S	1.000
12:123659912:T:C	C268R	1.000
12:123659913:G:A	C268Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000001429 (12:123636097 G>C), RS1000049272 (12:123646708 C>A,G), RS1000110298 (12:123640164 C>G,T), RS1000409499 (12:123633489 G>A,C), RS1000460650 (12:123640004 G>A), RS1000587541 (12:123644730 A>G), RS1000853537 (12:123638232 C>T), RS1000898486 (12:123650737 G>A), RS1001197658 (12:123657969 G>T), RS1001198841 (12:123662989 C>A), RS1001257665 (12:123660409 T>G), RS1001399707 (12:123633709 G>A), RS1001466471 (12:123634882 A>G), RS1001777920 (12:123653660 AAAG>A), RS1001784248 (12:123638881 C>T)

Disease associations

OMIM: gene MIM:601750 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003815_64	Late-onset Alzheimer’s disease	8.000000e-06
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST90006990_3	Gut microbiota relative abundance (Prevotella)	8.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Tretinoin	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
CPG-oligonucleotide	decreases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

Clinical trials (associated diseases)

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