RNF113A

Summary

RNF113A (ring finger protein 113A, HGNC:12974) is a protein-coding gene on chromosome Xq24, encoding E3 ubiquitin-protein ligase RNF113A (O15541). Required for pre-mRNA splicing as component of the spliceosome. It is a common-essential gene (DepMap: required in 96.5% of cancer cell lines).

This intronless gene encodes a protein which contains a C3H1-type zinc finger domain and a C3HC4 Ring-type (Really Interesting New Gene-type) zinc finger domain. The Ring-type zinc finger domain is identified in various tumor suppressors, DNA repair genes and cytokine receptor-associated molecules, and is probably involved in mediating protein-protein interactions.

Source: NCBI Gene 7737 — RefSeq curated summary.

At a glance

• Gene–disease (curated): trichothiodystrophy 5, nonphotosensitive (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 109 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 118
• Cancer dependency (DepMap): dependent in 96.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_006978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12974
Approved symbol	RNF113A
Name	ring finger protein 113A
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	RNF113, Cwc24
Ensembl gene	ENSG00000125352
Ensembl biotype	protein_coding
OMIM	300951
Entrez	7737

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000371442

RefSeq mRNA: 1 — MANE Select: NM_006978 NM_006978

CCDS: CCDS14589

Canonical transcript exons

ENST00000371442 — 1 exons

Exon	Start	End
ENSE00001455235	119870475	119871733

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 93.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2551 / max 191.5387, expressed in 1805 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200321	16.6160	1799
200323	1.6391	1055

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.31	gold quality
leukocyte	CL:0000738	88.93	gold quality
monocyte	CL:0000576	88.75	gold quality
mononuclear cell	CL:0000842	88.71	gold quality
tendon of biceps brachii	UBERON:0008188	88.69	silver quality
parotid gland	UBERON:0001831	88.44	gold quality
blood	UBERON:0000178	87.81	gold quality
spleen	UBERON:0002106	86.47	gold quality
cortical plate	UBERON:0005343	86.41	gold quality
body of pancreas	UBERON:0001150	86.18	gold quality
mucosa of transverse colon	UBERON:0004991	85.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.94	gold quality
bone marrow	UBERON:0002371	84.84	gold quality
lymph node	UBERON:0000029	84.69	gold quality
oocyte	CL:0000023	84.64	gold quality
skin of leg	UBERON:0001511	84.46	gold quality
skin of abdomen	UBERON:0001416	84.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.75	gold quality
stromal cell of endometrium	CL:0002255	83.40	gold quality
pancreas	UBERON:0001264	83.27	gold quality
prefrontal cortex	UBERON:0000451	83.12	gold quality
descending thoracic aorta	UBERON:0002345	83.00	gold quality
tendon	UBERON:0000043	82.97	gold quality
popliteal artery	UBERON:0002250	82.80	gold quality
tibial artery	UBERON:0007610	82.80	gold quality
zone of skin	UBERON:0000014	82.70	gold quality
ganglionic eminence	UBERON:0004023	82.66	gold quality
gastrocnemius	UBERON:0001388	82.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.54	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.34
E-CURD-112	no	2.74

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• A mutation that resulted in significant reduction of RNF113A protein was implicated in a non-photosensitive form of trichothiodystrophy. Lymphoblastoid cell lines from patients with the mutation in RNF113A had normal DNA damage responses on exposure to mitomycin C, diepoxybutane (DEB), bromodeoxyuridine (BrdU) and irradiation with ultraviolet light. (PMID:25612912)
• RNF113A promotes the proliferation, migration and invasiveness of esophageal squamous cell carcinoma (ESCC) cell lines. RNF113A expression in ESCC is associated with a poor prognosis of affected patients. (PMID:29393393)
• Second report of RING finger protein 113A (RNF113A) involvement in a Mendelian disorder. (PMID:31793730)
• A novel truncating variant in ring finger protein 113A (RNF113A) confirms the association of this gene with X-linked trichothiodystrophy. (PMID:31880405)
• Ring Finger Protein 11 acts on ligand-activated EGFR via the direct interaction with the UIM region of ANKRD13 protein family. (PMID:31985874)
• RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1. (PMID:32152280)
• SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation Cross-talk. (PMID:35819319)
• RNF113A targeted by miR-197 promotes proliferation and inhibits autophagy via CXCR4/CXCL12/AKT/ERK/Beclin1 axis in cervical cancer. (PMID:37164050)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf113a	ENSDARG00000037930
mus_musculus	Rnf113a1	ENSMUSG00000036537
mus_musculus	Rnf113a2	ENSMUSG00000098134
rattus_norvegicus	Rnf113a1	ENSRNOG00000066548
rattus_norvegicus	Rnf113a2	ENSRNOG00000067995
drosophila_melanogaster	mdlc	FBGN0038772
caenorhabditis_elegans		WBGENE00010476

Paralogs (1): RNF113B (ENSG00000139797)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF113A — O15541 (reviewed: O15541)

Alternative names: Cwc24 homolog, RING finger protein 113A, Zinc finger protein 183

All UniProt accessions (1): O15541

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin onto target proteins. Catalyzes polyubiquitination of SNRNP200/BRR2 with non-canonical ‘Lys-63’-linked polyubiquitin chains. Plays a role in DNA repair via its role in the synthesis of ‘Lys-63’-linked polyubiquitin chains that recruit ALKBH3 and the ASCC complex to sites of DNA damage by alkylating agents. Ubiquitinates CXCR4, leading to its degradation, and thereby contributes to the termination of CXCR4 signaling.

Subunit / interactions. Component of pre-catalytic and catalytic spliceosome complexes. Interacts (via N-terminus) with the spliceosome subunit SNRNP200/BRR2. Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with SCNM1 and CRIPT.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Ubiquitous.

Disease relevance. Trichothiodystrophy 5, non-photosensitive (TTD5) [MIM:300953] An X-linked form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD5 features include microcephaly, profound intellectual disability, sparse brittle hair, aged appearance, short stature, facial dysmorphism, seizures, an immunoglobulin deficiency, multiple endocrine abnormalities, cerebellar hypoplasia and partial absence of the corpus callosum, in the absence of cellular photosensitivity and ichthyosis. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_008909* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR039971	CWC24-like	Family

Pfam: PF00642, PF13920

UniProt features (40 total): helix 7, mutagenesis site 6, strand 6, modified residue 5, compositionally biased region 4, region of interest 4, turn 3, zinc finger region 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7DVQ	ELECTRON MICROSCOPY	2.89
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
8I0U	ELECTRON MICROSCOPY	3.3
6FF4	ELECTRON MICROSCOPY	3.4
8I0S	ELECTRON MICROSCOPY	4.2
6FF7	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
5Z56	ELECTRON MICROSCOPY	5.1
8CH6	ELECTRON MICROSCOPY	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15541-F1	69.65	0.15

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 (5): 2, 6, 84, 85, 253

Mutagenesis-validated functional residues (6):

Position	Phenotype
2–60	strongly decreased interaction with snrnp200/brr2.
50–61	strongly decreased interaction with cxcr4. abolishes the ability to promote cxcr4 degradation.
262	loss of e3 ubiquitin ligase activity.
264	strongly reduced e3 ubiquitin ligase activity.
277	loss of e3 ubiquitin ligase activity.
301–343	cells are hypersensitive to dna damage by alkylating agents.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 397 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_RESPONSE_TO_PEPTIDE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, EVI1_05, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, REACTOME_MRNA_SPLICING, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_CYTOKINE_STIMULUS, HAND1E47_01, GOBP_REGULATION_OF_RESPONSE_TO_CYTOKINE_STIMULUS, KAYO_AGING_MUSCLE_UP

GO Biological Process (8): mRNA splicing, via spliceosome (GO:0000398), DNA repair (GO:0006281), protein ubiquitination (GO:0016567), snoRNA splicing (GO:0034247), negative regulation of chemokine-mediated signaling pathway (GO:0070100), mRNA processing (GO:0006397), DNA damage response (GO:0006974), RNA splicing (GO:0008380)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), U2-type spliceosomal complex (GO:0005684), nuclear speck (GO:0016607), U2-type precatalytic spliceosome (GO:0071005), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
DNA metabolic process	1
DNA damage response	1
protein modification by small protein conjugation	1
RNA splicing	1
sno(s)RNA processing	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
chemokine-mediated signaling pathway	1
regulation of chemokine-mediated signaling pathway	1
mRNA metabolic process	1
cellular response to stress	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
spliceosomal complex	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1239 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF113A	CWC27	Q6UX04	864
RNF113A	CWC25	Q9NXE8	843
RNF113A	CWC22	Q9HCG8	825
RNF113A	SF3A2	Q15428	781
RNF113A	CDC5L	Q99459	780
RNF113A	YJU2	Q9BW85	776
RNF113A	BUD13	Q9BRD0	774
RNF113A	CWC15	Q9P013	755
RNF113A	PIH1D1	Q9NWS0	739
RNF113A	SF3B2	Q13435	713
RNF113A	MPLKIP	Q8TAP9	708
RNF113A	SNRNP200	O75643	694
RNF113A	DHX38	Q92620	690
RNF113A	SLU7	O95391	675
RNF113A	DHX16	O60231	641
RNF113A	PRPF18	Q99633	641

IntAct

34 interactions, top by confidence:

A	B	Type	Score
RBM8A	CASC3	psi-mi:“MI:0914”(association)	0.900
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RNF113A	CSNK2A2	psi-mi:“MI:0914”(association)	0.530
SNRNP200	RNF113A	psi-mi:“MI:0915”(physical association)	0.510
IK	RNF113A	psi-mi:“MI:0915”(physical association)	0.510
SF3B2	RNF113A	psi-mi:“MI:0915”(physical association)	0.510
RNF113A	CANX	psi-mi:“MI:0915”(physical association)	0.400
RNF113A	EIF3J	psi-mi:“MI:0915”(physical association)	0.400
TERF2	RNF113A	psi-mi:“MI:0915”(physical association)	0.370
RNF113A	UBE2U	psi-mi:“MI:0915”(physical association)	0.370
TRIM8	RNF113A	psi-mi:“MI:0915”(physical association)	0.370
CCAR1	RNF113A	psi-mi:“MI:0915”(physical association)	0.370
RNF113A	RBM39	psi-mi:“MI:0915”(physical association)	0.370
ILF3	RNF113A	psi-mi:“MI:0915”(physical association)	0.370
Rcc1	WDR46	psi-mi:“MI:0914”(association)	0.350
PCDH7	RNF113A	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
RDX	RNF113A	psi-mi:“MI:0914”(association)	0.350
CARNMT1	LENG9	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
ARMC7	RNF113A	psi-mi:“MI:0915”(physical association)	0.320
LMNA	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
LMNA	SUPT5H	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (734): RNF113A (Affinity Capture-MS), RNF113A (Proximity Label-MS), RNF113A (Affinity Capture-MS), RNF113A (Affinity Capture-MS), RNF113A (Affinity Capture-MS), RNF113A (Affinity Capture-MS), RNF113A (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), AASDH (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), RNF113A (Affinity Capture-MS), RNF113A (Affinity Capture-MS), RNF113A (Affinity Capture-Western), CXCR4 (Reconstituted Complex)

ESM2 similar proteins: A4IGY3, A7SD85, A8WMM4, E1C760, F4ICK8, O08837, O15541, O48713, P19351, P92948, Q0JHZ2, Q0VFP5, Q12000, Q16543, Q1RMM1, Q28Y69, Q2KJC1, Q2KJD3, Q3TIV5, Q3TQI7, Q54DA5, Q568A0, Q5BH88, Q5BJP2, Q5EAC6, Q5H7N8, Q5PQS7, Q5RC87, Q5RE65, Q67ER4, Q6A068, Q6DD06, Q6DKE6, Q6NUB2, Q6U6G5, Q7JWR9, Q803J8, Q8GX84, Q8WU90, Q93618

Diamond homologs: O15541, O17917, P0CQ64, P0CQ65, P53769, Q02398, Q1JPS1, Q4P400, Q4WUA0, Q55G16, Q5ACW2, Q5AVC5, Q67ER4, Q6BYU0, Q6CB23, Q6CSS6, Q6FXX1, Q6K4V3, Q752S4, Q7SDY3, Q8GX84, Q8IZP6, Q9FNG6, Q9P6R8, Q03605, O74747, G2Q0E2, P33288, Q1XHU0, Q6FPI4, Q6MFZ5, Q75EN0, Q7ZWF4, Q9ESN2, Q9HCM9, A0JN74, A6NGJ6, A6NI03, A6NLI5, B1H278

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF113A	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
mRNA Splicing - Major Pathway	9	17.6×	2e-07
mRNA Polyadenylation	5	15.7×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	5	14.7×	1e-03
Dengue Virus-Host Interactions	5	8.2×	7e-03
Metabolism of RNA	5	7.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	7	19.4×	1e-05
RNA splicing	6	16.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	79
Likely benign	19
Benign	3

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
872888	NM_006978.3(RNF113A):c.897_898del (p.Cys299_Asp300delinsTer)	Pathogenic
1701072	NM_006978.3(RNF113A):c.861del (p.Gln288fs)	Likely pathogenic
192382	NM_006978.3(RNF113A):c.901C>T (p.Gln301Ter)	Likely pathogenic
2578338	NM_006978.3(RNF113A):c.890_891del (p.Tyr297fs)	Likely pathogenic
420812	NM_006978.3(RNF113A):c.836A>G (p.His279Arg)	Likely pathogenic

SpliceAI

119 predictions. Top by Δscore:

Variant	Effect	Δscore
X:119871724:G:GT	donor_gain	0.9200
X:119871563:G:GT	donor_gain	0.8600
X:119871564:A:T	donor_gain	0.8000
X:119870859:C:A	donor_gain	0.6900
X:119870912:A:AC	donor_gain	0.6900
X:119870913:C:CC	donor_gain	0.6900
X:119870779:G:A	donor_gain	0.6400
X:119870858:T:TA	donor_gain	0.6300
X:119870776:AATG:A	donor_gain	0.6100
X:119870896:G:GT	donor_gain	0.6100
X:119870966:G:C	donor_gain	0.6000
X:119870844:T:TA	donor_gain	0.5800
X:119870850:T:C	donor_gain	0.5800
X:119870913:CGTT:C	donor_gain	0.5800
X:119871730:G:GT	donor_gain	0.5300
X:119870601:T:TA	donor_gain	0.5200
X:119870841:ATTT:A	donor_gain	0.5200
X:119870788:TGGTG:T	donor_gain	0.5100
X:119870877:T:TA	donor_gain	0.5100
X:119870865:T:TA	donor_gain	0.5000
X:119870858:TCCC:T	donor_gain	0.4900
X:119870898:C:A	donor_gain	0.4900
X:119870907:AG:A	donor_gain	0.4800
X:119870924:C:CT	donor_gain	0.4800
X:119870892:TAGCG:T	donor_gain	0.4700
X:119870893:AGCGA:A	donor_gain	0.4700
X:119870904:T:C	donor_gain	0.4600
X:119870925:C:CT	donor_gain	0.4500
X:119871001:AGT:A	donor_gain	0.4500
X:119870862:A:AC	donor_gain	0.4400

AlphaMissense

2286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:119870953:G:C	H221D	1.000
X:119870953:G:T	H221N	1.000
X:119870957:G:C	F219L	1.000
X:119870957:G:T	F219L	1.000
X:119870958:A:C	F219C	1.000
X:119870958:A:G	F219S	1.000
X:119870959:A:G	F219L	1.000
X:119870963:G:C	C217W	1.000
X:119870964:C:A	C217F	1.000
X:119870964:C:G	C217S	1.000
X:119870964:C:T	C217Y	1.000
X:119870965:A:G	C217R	1.000
X:119870965:A:T	C217S	1.000
X:119870975:G:C	F213L	1.000
X:119870975:G:T	F213L	1.000
X:119870977:A:G	F213L	1.000
X:119870982:C:G	C211S	1.000
X:119870982:C:T	C211Y	1.000
X:119870983:A:G	C211R	1.000
X:119870983:A:T	C211S	1.000
X:119871005:C:A	K203N	1.000
X:119871005:C:G	K203N	1.000
X:119871008:A:C	C202W	1.000
X:119871009:C:A	C202F	1.000
X:119871009:C:G	C202S	1.000
X:119871009:C:T	C202Y	1.000
X:119871010:A:G	C202R	1.000
X:119871010:A:T	C202S	1.000
X:119871031:A:G	W195R	1.000
X:119871031:A:T	W195R	1.000

dbSNP variants (sampled 300 via entrez): RS1001126389 (X:119871222 T>C), RS1002715819 (X:119872182 C>T), RS1005065580 (X:119870035 C>G,T), RS1006724363 (X:119873115 T>C), RS1007623548 (X:119872238 T>C), RS1009482383 (X:119871204 C>G), RS1013032084 (X:119872146 G>A), RS1013769319 (X:119870132 T>G), RS1013983295 (X:119870346 T>C), RS1015140104 (X:119870041 A>G), RS1015586824 (X:119872483 G>A), RS1016593852 (X:119870444 C>G,T), RS1017586786 (X:119871898 G>A,C), RS1019443510 (X:119873521 T>A,C), RS1023369687 (X:119872154 C>G,T)

Disease associations

OMIM: gene MIM:300951 | disease phenotypes: MIM:300953

GenCC curated gene-disease

Disease	Classification	Inheritance
trichothiodystrophy 5, nonphotosensitive	Strong	X-linked
trichothiodystrophy	Supportive	Autosomal recessive

Mondo (2): trichothiodystrophy 5, nonphotosensitive (MONDO:0010495), trichothiodystrophy (MONDO:0018053)

Orphanet (1): Trichothiodystrophy (Orphanet:33364)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000133	Gonadal dysgenesis
HP:0000154	Wide mouth
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000320	Bird-like facies
HP:0000348	High forehead
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000509	Conjunctivitis
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000556	Retinal dystrophy
HP:0000565	Esotropia
HP:0000601	Hypotelorism
HP:0000608	Macular degeneration
HP:0000609	Optic nerve hypoplasia
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000656	Ectropion
HP:0000670	Carious teeth

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
urushiol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
(+)-JQ1 compound	increases expression	1
Adenine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Colchicine	decreases expression	1
Diuron	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Etoposide	decreases expression	1
Formaldehyde	increases expression	1
Hydroxyurea	decreases expression	1
Lead	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases phosphorylation	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Vitamin E	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001813	Not specified	COMPLETED	Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
NCT05484570	Not specified	RECRUITING	Natural History Study for DNA Repair Disorders