GTF2H4

Summary

GTF2H4 (general transcription factor IIH subunit 4, HGNC:4658) is a protein-coding gene on chromosome 6p21.33, encoding General transcription factor IIH subunit 4 (Q92759). 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 common-essential gene (DepMap: required in 95.3% of cancer cell lines).

Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex.

Source: NCBI Gene 2968 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 66 total — 2 pathogenic
• Phenotypes (HPO): 24
• Cancer dependency (DepMap): dependent in 95.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_001517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4658
Approved symbol	GTF2H4
Name	general transcription factor IIH subunit 4
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	TFB2, TFIIH, P52
Ensembl gene	ENSG00000213780
Ensembl biotype	protein_coding
OMIM	601760
Entrez	2968

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000259895, ENST00000376316, ENST00000453897, ENST00000475845, ENST00000483318, ENST00000487746, ENST00000903713, ENST00000903714, ENST00000903715, ENST00000903716, ENST00000903717, ENST00000903718, ENST00000924708, ENST00000924709, ENST00000942992, ENST00000942993, ENST00000942994

RefSeq mRNA: 1 — MANE Select: NM_001517 NM_001517

CCDS: CCDS34386

Canonical transcript exons

ENST00000259895 — 14 exons

Exon	Start	End
ENSE00001670495	30912328	30912458
ENSE00001711912	30912014	30912146
ENSE00001910828	30908207	30908403
ENSE00003487930	30911684	30911767
ENSE00003496467	30911158	30911269
ENSE00003512505	30913811	30914106
ENSE00003513404	30909932	30910063
ENSE00003539036	30909435	30909539
ENSE00003543566	30911431	30911499
ENSE00003547708	30913309	30913387
ENSE00003581567	30910853	30910941
ENSE00003581740	30910665	30910761
ENSE00003690053	30913110	30913157
ENSE00003770988	30909034	30909173

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 91.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.9870 / max 283.2635, expressed in 1800 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66836	28.9870	1800

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	91.93	gold quality
pituitary gland	UBERON:0000007	91.84	gold quality
metanephros cortex	UBERON:0010533	91.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.32	gold quality
cerebellar hemisphere	UBERON:0002245	90.92	gold quality
cerebellar cortex	UBERON:0002129	90.88	gold quality
cerebellum	UBERON:0002037	90.83	gold quality
adenohypophysis	UBERON:0002196	90.73	gold quality
left lobe of thyroid gland	UBERON:0001120	90.39	gold quality
right lobe of thyroid gland	UBERON:0001119	90.25	gold quality
thyroid gland	UBERON:0002046	90.19	gold quality
cortical plate	UBERON:0005343	90.13	gold quality
tibial artery	UBERON:0007610	89.97	gold quality
body of uterus	UBERON:0009853	89.97	gold quality
popliteal artery	UBERON:0002250	89.96	gold quality
right coronary artery	UBERON:0001625	89.56	gold quality
apex of heart	UBERON:0002098	89.43	gold quality
tibial nerve	UBERON:0001323	89.36	gold quality
smooth muscle tissue	UBERON:0001135	89.28	gold quality
left coronary artery	UBERON:0001626	89.28	gold quality
fundus of stomach	UBERON:0001160	89.26	gold quality
descending thoracic aorta	UBERON:0002345	89.22	gold quality
ascending aorta	UBERON:0001496	89.21	gold quality
thoracic aorta	UBERON:0001515	89.19	gold quality
myometrium	UBERON:0001296	88.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.80	gold quality
endocervix	UBERON:0000458	88.56	gold quality
right ovary	UBERON:0002118	88.54	gold quality
liver	UBERON:0002107	88.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4

miRNA regulators (miRDB)

4 targeting GTF2H4, 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-4477A	98.83	69.75	2952
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-7108-3P	94.37	64.79	183

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 18)

• General transcription factor IIH protects promoters from PC4-mediated repression by relieving the topological constraint imposed by PC4 through the ERCC3 helicase activity rather than by reducing the repressive activity of PC4 via its phosphorylation. (PMID:12590132)
• The second domain of TFIIH p62 subunit(residues 186-240) contains a region of high sequence conservation with an invariant tyrosine/phenylalanine motif which could play a key role as a protein-protein recognition module within TFIIH. (PMID:15533047)
• TFIIH uses an expanded proximal promoter to regulate c-myc expression (PMID:15601838)
• We conclude that the recruitment and activation of TFIIH represents a rate-limiting step for the emergence of HIV from latency. (PMID:16874302)
• Alterations of chromatin at the RNA polymerase II stall site, which depend on CSB and TFIIH at least, are necessary for the UV-induced translocation of CSA to the nuclear matrix. (PMID:17242193)
• XPG forms a stable complex with TFIIH, which is active in transcription and nucleotide excision repair (PMID:17466625)
• mechanism in which the helicase activity of XPB is not used for the opening and repair of damaged DNA, which is instead only driven by its ATPase activity, in combination with the helicase activity of XPD (PMID:17466626)
• The specific binding of the C-terminal acidic domain (AC-D) of the human TFIIEalpha subunit to the pleckstrin homology domain (PH-D) of the human TFIIH p62 subunit is demonstrated. (PMID:18354501)
• TAF7 interacts with the transcription factors, TFIIH and P-TEFb, resulting in the inhibition of their Pol II CTD kinase activities (PMID:18391197)
• TFIIH changes subunit composition in response to DNA damage. The CAK is released from the core during nucleotide excision repair (NER). (PMID:18614043)
• For 6-4 photoproducts, we show that TFIIH complexes carrying an NH(2)-terminal XPD mutated protein are also deficient in recruitment of NER proteins downstream of TFIIH (PMID:18676829)
• The frequency of congenital ichthyosis, collodion-baby type, was significantly higher in the TFIIH mutated group of trichothiodystrophy patients. (PMID:19681155)
• Study demonstrates that an essential initiation factor, TFB2, forms a network of interactions with DNA near the transcription start site and facilitates promoter melting but may not be essential for promoter recognition. (PMID:19945377)
• A single nucleotide polymorphism variant within the general transcription factor IIH, polypeptide 4 gene, GTF2H4, on chromosome 6p21.33 was significantly associated with MS (PMID:20522537)
• GTF2H4 variants may not be associated with susceptibility to aspirin-exacerbated respiratory disease and obstructive symptoms in asthmatics. (PMID:22524621)
• functional genetic variants of GTF2H4 confer susceptibility to lung cancer. (PMID:27288692)
• Data demonstrates gene expression changes in differentially methylated GTF2H4 gene in patients with age-related macular degeneration. (PMID:30642396)
• The role of Transcription Factor IIH complex in nucleotide excision repair. (PMID:37545038)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2h4	ENSDARG00000036071
mus_musculus	Gtf2h4	ENSMUSG00000001524
rattus_norvegicus	Gtf2h4	ENSRNOG00000000831
drosophila_melanogaster	mrn	FBGN0261109
caenorhabditis_elegans		WBGENE00013529

Protein

Protein identifiers

General transcription factor IIH subunit 4 — Q92759 (reviewed: Q92759)

Alternative names: Basic transcription factor 2 52 kDa subunit, General transcription factor IIH polypeptide 4, TFIIH basal transcription factor complex p52 subunit

All UniProt accessions (2): A0A1U9X7S4, Q92759

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. Stimulates the ATPase activity of TFIIH subunit XPB/ERCC3.

Subunit / interactions. 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. Part of TBP-based Pol II pre-initiation complex (PIC), in which Pol II core assembles with general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms.

Subcellular location. Nucleus.

Domain organisation. The C-terminus (residues 305-462) stimulates the ATPase activity of XPB/ERCC3.

Similarity. Belongs to the TFB2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92759-1	1	yes
Q92759-2	2

RefSeq proteins (1): NP_001508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004598	TFIIH_p52/Tfb2	Family
IPR040662	Tfb2_C	Domain

Pfam: PF03849, PF18307

UniProt features (47 total): helix 22, strand 17, splice variant 3, turn 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7NVV	ELECTRON MICROSCOPY	2.9
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
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-Q92759-F1	85.85	0.51

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: 238 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, KAUFFMANN_DNA_REPAIR_GENES, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOTIDE_EXCISION_REPAIR, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, REACTOME_HIV_INFECTION, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_UP, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, BENPORATH_ES_CORE_NINE_CORRELATED

GO Biological Process (4): DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), transcription by RNA polymerase II (GO:0006366), DNA damage response (GO:0006974)

GO Molecular Function (4): ATPase activator activity (GO:0001671), double-stranded DNA binding (GO:0003690), RNA polymerase II general transcription initiation factor activity (GO:0016251), protein binding (GO:0005515)

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), nuclear speck (GO:0016607)

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
transcription factor TFIIH core complex	2
RNA polymerase II, holoenzyme	2
DNA metabolic process	1
DNA damage response	1
DNA repair	1
DNA-templated transcription	1
cellular response to stress	1
ATP-dependent activity	1
molecular function activator activity	1
DNA binding	1
transcription by RNA polymerase II	1
general transcription initiation factor activity	1
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
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2H4	GTF2H1	P32780	999
GTF2H4	GTF2H2	Q13888	999
GTF2H4	ERCC3	P19447	998
GTF2H4	ERCC2	P18074	997
GTF2H4	GTF2H3	Q13889	997
GTF2H4	GTF2H5	Q6ZYL4	995
GTF2H4	CCNH	P51946	959
GTF2H4	MNAT1	P51948	931
GTF2H4	CDK7	P50613	885
GTF2H4	XPA	P23025	763
GTF2H4	GTF2H2C	Q6P1K8	738
GTF2H4	PUF60	Q9UHX1	670
GTF2H4	TFAM	Q00059	667
GTF2H4	GTF2B	Q00403	625
GTF2H4	A0A090J7P6	A0A090J7P6	623

IntAct

71 interactions, top by confidence:

A	B	Type	Score
GTF2H5	GTF2H4	psi-mi:“MI:0915”(physical association)	0.860
GTF2H1	CDK7	psi-mi:“MI:0915”(physical association)	0.820
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
GTF2H5	GTF2H1	psi-mi:“MI:0914”(association)	0.730
ERCC2	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
EAF1	GTF2H4	psi-mi:“MI:0915”(physical association)	0.670
GTF2H4	EAF1	psi-mi:“MI:0915”(physical association)	0.670
GTF2H4	GTF2H1	psi-mi:“MI:0914”(association)	0.670
GTF2H5	ERCC2	psi-mi:“MI:0914”(association)	0.650
GTF2H3	ERCC3	psi-mi:“MI:0914”(association)	0.640
GTF2H2	ERCC2	psi-mi:“MI:0914”(association)	0.620
THAP3	GTF2H4	psi-mi:“MI:0915”(physical association)	0.620
SREK1IP1	GTF2H4	psi-mi:“MI:0915”(physical association)	0.560
EIF1AD	GTF2H4	psi-mi:“MI:0915”(physical association)	0.560
GTF2H4	ERCC2	psi-mi:“MI:0914”(association)	0.530
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
ERCC3	BCR	psi-mi:“MI:0914”(association)	0.530
GTF2H2C	ERCC3	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
GTF2H5	GTF2H3	psi-mi:“MI:0914”(association)	0.350

BioGRID (168): GTF2H4 (Affinity Capture-MS), GTF2H4 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H4 (Affinity Capture-MS), GTF2H4 (Affinity Capture-MS), GTF2H4 (Affinity Capture-MS), GTF2H4 (Affinity Capture-MS), GTF2H4 (Affinity Capture-MS), GTF2H4 (Affinity Capture-MS), GTF2H4 (Affinity Capture-Western), GTF2H5 (Reconstituted Complex)

ESM2 similar proteins: A4F267, A6QR22, E9PZQ0, F1LMY4, O70422, O96008, P07144, P11716, P16960, P21817, P42054, P42055, P42056, P45880, P46274, P60027, P68002, P68003, P81155, P82013, P86223, Q0JNK5, Q1LZB5, Q29380, Q53PC7, Q5E9L7, Q5R7V4, Q5U3I0, Q60930, Q60931, Q6K548, Q6P825, Q75Q40, Q7F4F8, Q7ZTM6, Q91W86, Q920Q4, Q92759, Q969M1, Q9CZR3

Diamond homologs: O70422, P60027, P87303, Q02939, Q54C29, Q680U9, Q6BGW8, Q6BZX4, Q6CLR2, Q6FP41, Q75B51, Q92759

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF2H4	“form complex”	TFIIH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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	110.2×	5e-17
RNA Pol II CTD phosphorylation and interaction with CE	10	110.2×	5e-17
mRNA Capping	10	102.9×	7e-17
Formation of the Early Elongation Complex	10	90.8×	1e-16
Formation of the HIV-1 Early Elongation Complex	10	90.8×	1e-16
Global Genome Nucleotide Excision Repair (GG-NER)	7	86.4×	1e-11
Formation of Incision Complex in GG-NER	12	82.3×	2e-18
RNA Polymerase I Transcription Termination	9	79.4×	1e-14

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	11	86.0×	1e-16
transcription initiation at RNA polymerase II promoter	10	76.4×	9e-15
transcription by RNA polymerase II	9	12.9×	3e-06
DNA repair	7	9.1×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4533342	GTF2H4, IVS2, G-A, -1	Pathogenic
4533343	GTF2H4, 2-BP DEL/3-BP INS, NT 1203	Pathogenic

SpliceAI

1601 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30909428:T:TA	acceptor_gain	1.0000
6:30909430:TACA:T	acceptor_loss	1.0000
6:30909431:A:AG	acceptor_gain	1.0000
6:30909431:ACAG:A	acceptor_gain	1.0000
6:30909431:ACAGG:A	acceptor_gain	1.0000
6:30909432:C:G	acceptor_gain	1.0000
6:30909432:CA:C	acceptor_loss	1.0000
6:30909432:CAGGG:C	acceptor_gain	1.0000
6:30909433:A:AG	acceptor_gain	1.0000
6:30909433:A:AT	acceptor_loss	1.0000
6:30909433:AG:A	acceptor_gain	1.0000
6:30909433:AGG:A	acceptor_gain	1.0000
6:30909433:AGGGA:A	acceptor_gain	1.0000
6:30909434:G:GA	acceptor_gain	1.0000
6:30909434:GG:G	acceptor_gain	1.0000
6:30909434:GGG:G	acceptor_gain	1.0000
6:30909434:GGGA:G	acceptor_gain	1.0000
6:30909434:GGGAG:G	acceptor_gain	1.0000
6:30909536:GCAA:G	donor_gain	1.0000
6:30909537:CAA:C	donor_gain	1.0000
6:30909539:AGTAA:A	donor_loss	1.0000
6:30909540:G:GG	donor_gain	1.0000
6:30909540:GTA:G	donor_loss	1.0000
6:30909541:TAA:T	donor_loss	1.0000
6:30909930:A:AG	acceptor_gain	1.0000
6:30909930:AG:A	acceptor_gain	1.0000
6:30909930:AGG:A	acceptor_gain	1.0000
6:30909931:G:A	acceptor_gain	1.0000
6:30909931:G:GA	acceptor_gain	1.0000
6:30909931:GGG:G	acceptor_gain	1.0000

AlphaMissense

3000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:30909159:T:G	C41W	1.000
6:30910042:T:C	L118P	1.000
6:30910733:T:A	L148H	1.000
6:30910745:C:A	A152D	1.000
6:30910756:T:A	W156R	1.000
6:30910756:T:C	W156R	1.000
6:30910758:G:C	W156C	1.000
6:30910758:G:T	W156C	1.000
6:30911195:G:C	G200R	1.000
6:30911196:G:A	G200D	1.000
6:30911198:T:C	F201L	1.000
6:30911200:C:A	F201L	1.000
6:30911200:C:G	F201L	1.000
6:30911204:T:C	F203L	1.000
6:30911205:T:C	F203S	1.000
6:30911206:C:A	F203L	1.000
6:30911206:C:G	F203L	1.000
6:30911208:T:C	L204P	1.000
6:30911727:T:C	L262P	1.000
6:30911736:T:C	L265P	1.000
6:30911747:G:A	G269R	1.000
6:30911747:G:C	G269R	1.000
6:30911747:G:T	G269W	1.000
6:30911748:G:A	G269E	1.000
6:30911748:G:T	G269V	1.000
6:30911754:T:A	V271D	1.000
6:30911763:G:C	R274T	1.000
6:30911763:G:T	R274M	1.000
6:30911764:G:C	R274S	1.000
6:30911764:G:T	R274S	1.000

dbSNP variants (sampled 300 via entrez): RS1000147397 (6:30909929 C>A,T), RS1000838947 (6:30914276 G>A), RS1001601716 (6:30910421 C>G), RS1001623670 (6:30908981 G>C), RS1001909214 (6:30907983 G>C), RS1001940463 (6:30908204 T>C), RS1003017365 (6:30911940 A>G), RS1005424937 (6:30909913 C>T), RS1005658139 (6:30912991 A>G), RS1006013568 (6:30911868 G>A), RS1006316243 (6:30908202 T>C), RS1006661418 (6:30914317 C>T), RS1007677254 (6:30914364 G>A,T), RS1008790953 (6:30912042 G>A), RS1009721713 (6:30908612 A>C)

Disease associations

OMIM: gene MIM:601760 | disease phenotypes: MIM:621435

GenCC curated gene-disease

Mondo (1): xeroderma pigmentosum, complementation group J (MONDO:0980987)

Orphanet (0):

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000490	Deeply set eye
HP:0000613	Photophobia
HP:0000750	Delayed speech and language development
HP:0000958	Dry skin
HP:0000992	Cutaneous photosensitivity
HP:0001003	Multiple lentigines
HP:0001059	Pterygium
HP:0001256	Mild intellectual disability
HP:0001518	Small for gestational age
HP:0001595	Abnormal hair morphology
HP:0001597	Abnormal nail morphology
HP:0001882	Decreased total leukocyte count
HP:0001903	Anemia
HP:0002527	Falls
HP:0002750	Delayed skeletal maturation
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0008064	Ichthyosis
HP:0010783	Erythema
HP:0011342	Mild global developmental delay
HP:0031936	Delayed ability to walk
HP:0100699	Scarring

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000853_3	Ulcerative colitis	4.000000e-06
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_131	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_132	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_19	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_27	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_33	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004521_48	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004723_2	Conotruncal heart defects (maternal effects)	3.000000e-07
GCST004723_3	Conotruncal heart defects (maternal effects)	8.000000e-07
GCST004946_173	Schizophrenia	2.000000e-08
GCST005541_14	Sarcoidosis (Lofgren’s syndrome vs non-Lofgren’s syndrome)	2.000000e-24
GCST010725_70	Malaria	5.000000e-06
GCST010725_9	Malaria	6.000000e-06

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
bisphenol A	increases abundance, affects cotreatment, increases methylation, decreases expression, increases expression (+1 more)	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
Cyclosporine	increases expression	2
ginger extract	decreases reaction, increases abundance, increases expression	1
2,4,6-tribromophenol	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
tetrabromobisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
CPG-oligonucleotide	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
Resveratrol	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment, increases methylation	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Coumestrol	increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diclofenac	affects expression	1
Ellagic Acid	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Niclosamide	decreases expression, increases expression	1
Oils, Volatile	decreases reaction, increases abundance, increases expression	1
Quercetin	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2J0	SEES3-1V human GTF2H4, clone1	Embryonic stem cell	Male
CVCL_A2J1	SEES3-1V human GTF2H4, clone2	Embryonic stem cell	Male
CVCL_A2J2	SEES3-1V human GTF2H4, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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