GTF2H2C_2

Summary

GTF2H2C_2 (GTF2H2 family member C, copy 2, HGNC:35418) is a protein-coding gene on chromosome 5q13.2 alternate reference locus, encoding General transcription factor IIH subunit 2-like protein (Q6P1K8). Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.

Predicted to enable zinc ion binding activity. Predicted to be involved in nucleotide-excision repair and regulation of transcription by RNA polymerase II. Located in nuclear speck.

Source: NCBI Gene 730394 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001354437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35418
Approved symbol	GTF2H2C_2
Name	GTF2H2 family member C, copy 2
Location	5q13.2 alternate reference locus
Locus type	gene with protein product
Status	Approved
Aliases	LOC730394
Ensembl gene	ENSG00000274675
Entrez	730394

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 4 — MANE Select: NM_001354437 NM_001042490, NM_001354437, NM_001354438, NM_001354439

Canonical transcript exons

ENST00000621406 — 0 exons

Expression profiles

Top tissues by expression

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

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	255.05

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

General transcription factor IIH subunit 2-like protein — Q6P1K8 (reviewed: Q6P1K8)

Alternative names: General transcription factor IIH polypeptide 2-like protein

All UniProt accessions (3): Q6P1K8, D6RAW1, D6RJD3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.

Subcellular location. Nucleus.

Similarity. Belongs to the GTF2H2 family.

RefSeq proteins (4): NP_001035955, NP_001341366, NP_001341367, NP_001341368 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR004595	TFIIH_C1-like_dom	Domain
IPR007198	Ssl1-like	Domain
IPR012170	TFIIH_SSL1/p44	Family
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF04056, PF07975

UniProt features (5 total): chain 1, domain 1, zinc finger region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1K8-F1	84.05	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 95

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_NUCLEOTIDE_EXCISION_REPAIR, GOBP_DNA_DAMAGE_RESPONSE, GOCC_RNA_POLYMERASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_CYCLIN_DEPENDENT_PROTEIN_KINASE_HOLOENZYME_COMPLEX, GOCC_TRANSFERASE_COMPLEX, GOCC_NUCLEAR_BODY, GOCC_PROTEIN_KINASE_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_CARBOXY_TERMINAL_DOMAIN_PROTEIN_KINASE_COMPLEX, GOBP_DNA_METABOLIC_PROCESS, GOCC_CYCLIN_DEPENDENT_PROTEIN_KINASE_HOLOENZYME_COMPLEX

GO Biological Process (5): nucleotide-excision repair (GO:0006289), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): transcription factor TFIIH core complex (GO:0000439), transcription factor TFIIH holo complex (GO:0005675), nuclear speck (GO:0016607), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2H2C_2	GTF2H3	Q13889	797
GTF2H2C_2	GTF2H1	P32780	770
GTF2H2C_2	ERCC3	P19447	754
GTF2H2C_2	GTF2H4	Q92759	738
GTF2H2C_2	ERCC8	Q13216	684
GTF2H2C_2	ERCC1	P07992	671
GTF2H2C_2	SERF1A	O75920	583
GTF2H2C_2	ERCC2	P18074	572
GTF2H2C_2	MNAT1	P51948	542
GTF2H2C_2	CDK7	P50613	530
GTF2H2C_2	NAIP	Q13075	506
GTF2H2C_2	FAM72B	Q86X60	474
GTF2H2C_2	SMN1	Q16637	474
GTF2H2C_2	DHRS4L2	Q6PKH6	473
GTF2H2C_2	TCAF1	Q9Y4C2	461

IntAct

41 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
GTF2H3	ERCC3	psi-mi:“MI:0914”(association)	0.640
ERCC2	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.560
DZIP3	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.560
GTF2H2C	ERCC2	psi-mi:“MI:0915”(physical association)	0.560
GTF2H2C	DZIP3	psi-mi:“MI:0915”(physical association)	0.560
GTF2H2C	FAM43A	psi-mi:“MI:0915”(physical association)	0.560
NR5A2	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.560
GTF2H2C	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
GTF2H2C	ERCC3	psi-mi:“MI:0914”(association)	0.530
DYNLRB2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.510
SUV39H1	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CCDC40	VAPB	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
CDK7	ACACB	psi-mi:“MI:0914”(association)	0.350
CDC7	ERCC1	psi-mi:“MI:0914”(association)	0.350
CDK7	ERCC1	psi-mi:“MI:0914”(association)	0.350
GTF2H4	TUSC2	psi-mi:“MI:0914”(association)	0.350
GTF2H4	HSPA8	psi-mi:“MI:0914”(association)	0.350
EAF1	C1orf226	psi-mi:“MI:0914”(association)	0.350
HIRIP3	GPX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): GTF2H2C_2 (Two-hybrid), GTF2H2C_2 (Two-hybrid), GTF2H2C_2 (Two-hybrid), GTF2H2C (Affinity Capture-MS), GTF2H1 (Affinity Capture-MS), GTF2H3 (Affinity Capture-MS), GTF2H4 (Affinity Capture-MS), ERCC3 (Affinity Capture-MS), PTS (Affinity Capture-MS), GALC (Affinity Capture-MS), GTF2H2C (Co-fractionation), GTF2H2C (Co-fractionation), GTF2H2C (Co-fractionation), GTF2H2C_2 (Co-fractionation), GTF2H2C_2 (Co-fractionation)

ESM2 similar proteins: A0A1L8F5J9, A0JN27, F1LTR1, F1NBL0, O15294, P35438, P35439, P56558, P61201, P61202, P61203, P61599, P61600, P63138, P79101, P81436, Q03555, Q05586, Q13888, Q15303, Q27HV0, Q2PFM2, Q2TBV5, Q4L208, Q58ED9, Q5R1P0, Q5SP67, Q5ZJ75, Q61527, Q62956, Q6IQT4, Q6IR75, Q6P1K8, Q6P632, Q7ZXR3, Q8BUV3, Q8C6G8, Q8CGY8, Q8R4D1, Q91854

Diamond homologs: A0JN27, O74995, P34567, Q04673, Q13888, Q2TBV5, Q6P1K8, Q86KZ2, Q9JIB4, Q9ZVN9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF2H2C	“form complex”	TFIIH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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	7	114.2×	9e-12
RNA Pol II CTD phosphorylation and interaction with CE	7	114.2×	9e-12
mRNA Capping	7	106.6×	1e-11
Formation of the Early Elongation Complex	7	94.0×	1e-11
Formation of the HIV-1 Early Elongation Complex	7	94.0×	1e-11
RNA Polymerase I Transcription Termination	7	91.4×	2e-11
Global Genome Nucleotide Excision Repair (GG-NER)	5	91.4×	1e-08
Formation of Incision Complex in GG-NER	8	81.2×	7e-12

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	8	98.8×	3e-12
transcription initiation at RNA polymerase II promoter	5	60.4×	2e-06
DNA repair	7	14.4×	4e-05
transcription by RNA polymerase II	6	13.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000330265 (5:71063919 A>C), RS1000927154 (5:71056263 G>C,T), RS1002328080 (5:71061435 C>T), RS1002931893 (5:71039973 A>G), RS1004375051 (5:71050736 G>A), RS1004810720 (5:71046348 A>C,G), RS1006464156 (5:71054969 T>C), RS1006891994 (5:71056093 T>C), RS1006926714 (5:71055231 T>C), RS1008471915 (5:71036515 TG>T), RS1008565273 (5:71063822 G>A), RS1008594959 (5:71061658 CT>C,CTT), RS1010264733 (5:71059415 G>A,C), RS1010574096 (5:71051944 T>C), RS1010606648 (5:71051209 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases expression	1
Gold	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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