ZRSR2

Summary

ZRSR2 (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2, HGNC:23019) is a protein-coding gene on chromosome Xp22.2, encoding U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 (Q15696). Pre-mRNA-binding protein required for splicing of both U2- and U12-type introns. It is a selective cancer dependency (DepMap: 89.1% of cell lines).

This gene encodes an essential splicing factor. The encoded protein associates with the U2 auxiliary factor heterodimer, which is required for the recognition of a functional 3’ splice site in pre-mRNA splicing, and may play a role in network interactions during spliceosome assembly.

Source: NCBI Gene 8233 — RefSeq curated summary.

At a glance

• Gene–disease (curated): orofaciodigital syndrome 21 (Strong, GenCC)
• Clinical variants (ClinVar): 136 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 91
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 89.1% of screened cell lines
• MANE Select transcript: NM_005089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23019
Approved symbol	ZRSR2
Name	zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	U2AF1-RS2, URP, ZC3H22
Ensembl gene	ENSG00000169249
Ensembl biotype	protein_coding
OMIM	300028
Entrez	8233

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000307771, ENST00000380308, ENST00000468028, ENST00000684799, ENST00000690252, ENST00000691502, ENST00000879159, ENST00000936516, ENST00000936517, ENST00000936518, ENST00000964212, ENST00000964213

RefSeq mRNA: 1 — MANE Select: NM_005089 NM_005089

CCDS: CCDS14172

Canonical transcript exons

ENST00000307771 — 11 exons

Exon	Start	End
ENSE00001268162	15818587	15818642
ENSE00001268197	15820207	15820316
ENSE00001268202	15815677	15815890
ENSE00001268223	15808233	15808271
ENSE00001298636	15790934	15791013
ENSE00001370906	15809200	15809318
ENSE00001404328	15822731	15823260
ENSE00001411662	15804111	15804197
ENSE00003575445	15803688	15803796
ENSE00003671067	15799872	15799953
ENSE00003900205	15790484	15790536

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5104 / max 143.5361, expressed in 1546 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195616	5.3358	1519
195617	0.1746	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.86	gold quality
granulocyte	CL:0000094	94.95	gold quality
monocyte	CL:0000576	94.57	gold quality
mononuclear cell	CL:0000842	94.44	gold quality
leukocyte	CL:0000738	94.03	gold quality
tendon of biceps brachii	UBERON:0008188	92.16	gold quality
lateral globus pallidus	UBERON:0002476	90.63	gold quality
popliteal artery	UBERON:0002250	90.04	gold quality
tibial artery	UBERON:0007610	90.04	gold quality
spleen	UBERON:0002106	89.82	gold quality
mucosa of stomach	UBERON:0001199	89.67	gold quality
descending thoracic aorta	UBERON:0002345	89.65	gold quality
aorta	UBERON:0000947	89.63	gold quality
lymph node	UBERON:0000029	89.42	gold quality
lower esophagus mucosa	UBERON:0035834	89.37	gold quality
adenohypophysis	UBERON:0002196	89.26	gold quality
ascending aorta	UBERON:0001496	89.21	gold quality
body of uterus	UBERON:0009853	89.15	gold quality
thoracic aorta	UBERON:0001515	89.14	gold quality
CA1 field of hippocampus	UBERON:0003881	89.08	gold quality
cardia of stomach	UBERON:0001162	88.95	gold quality
pituitary gland	UBERON:0000007	88.71	gold quality
globus pallidus	UBERON:0001875	88.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.54	gold quality
endocervix	UBERON:0000458	88.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.49	gold quality
hypothalamus	UBERON:0001898	88.47	gold quality
putamen	UBERON:0001874	88.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.44	gold quality
medial globus pallidus	UBERON:0002477	88.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.46

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Data show that through recognition of a common splicing element, Urp facilitates distinct steps of U2- and U12-type intron splicing. (PMID:21041408)
• In univariate analysis, mutated SRSF2 predicted shorter overall survival and more frequent acute myeloid leukemia progression compared with wild-type SRSF2, whereas mutated U2AF1, ZRSR2 had no impact on patient outcome. (PMID:22389253)
• ZRSR2 has a role in RNA splicing; dysregulated splicing of U12-type introns is a characteristic feature of ZRSR2 mutations in myelodysplastic syndrome (PMID:25586593)
• The mutational status of the SRSF2, U2AF1 and ZRSR2 did not affect the response rate or survival in MDS patients who had received first-line decitabine treatment. (PMID:25964599)
• We conclude that the common clinical features of patients with an isolated mutation of ZRSR2 are a macrocytic anemia without leukopenia, thrombocytopenia or an increase in marrow blast percentage (PMID:28942350)
• This meta-analysis indicates a positive effect of SF3B1 and an adverse prognostic effect of SRSF2, U2AF1, and ZRSR2 mutations in patients with myelodysplastic syndrome. (PMID:31124956)
• ZRSR2 mutation in a child with refractory macrocytic anemia and Down Syndrome. (PMID:31361176)
• ZRSR2 overexpression is a frequent and early event in castration-resistant prostate cancer development. (PMID:33568749)
• Sex-Biased ZRSR2 Mutations in Myeloid Malignancies Impair Plasmacytoid Dendritic Cell Activation and Apoptosis. (PMID:34615655)
• Global analysis of binding sites of U2AF1 and ZRSR2 reveals RNA elements required for mutually exclusive splicing by the U2- and U12-type spliceosome. (PMID:38088204)
• Differential alternative splicing analysis links variation in ZRSR2 to a novel type of oral-facial-digital syndrome. (PMID:38158857)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zrsr2	ENSDARG00000058448
mus_musculus	Gm73394	ENSMUSG00000121808
rattus_norvegicus	Zrsr2-ps1	ENSRNOG00000009639
drosophila_melanogaster	CG3294	FBGN0031628

Paralogs (2): U2AF1 (ENSG00000160201), U2AF1L4 (ENSG00000161265)

Protein

Protein identifiers

U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 — Q15696 (reviewed: Q15696)

Alternative names: CCCH type zinc finger, RNA-binding motif and serine/arginine rich protein 2, Renal carcinoma antigen NY-REN-20, U2(RNU2) small nuclear RNA auxiliary factor 1-like 2, U2AF35-related protein

All UniProt accessions (5): A0A8I5KRH1, A0A8I5KSD0, A0A8I5QKS0, A6NDW0, Q15696

UniProt curated annotations — full annotation on UniProt →

Function. Pre-mRNA-binding protein required for splicing of both U2- and U12-type introns. Selectively interacts with the 3’-splice site of U2- and U12-type pre-mRNAs and promotes different steps in U2 and U12 intron splicing. Recruited to U12 pre-mRNAs in an ATP-dependent manner and is required for assembly of the pre-spliceosome, a precursor to other spliceosomal complexes. For U2-type introns, it is selectively and specifically required for the second step of splicing.

Subunit / interactions. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Interacts (via RS domain) with SRSF1 and SRSF2. Interacts with U2AF2/U2AF65.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated in the RS domain by SRPK1.

Disease relevance. Orofaciodigital syndrome 21 (OFD21) [MIM:301132] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD21 is an X-linked recessive form characterized by postaxial polydactyly of the hands, hallux duplication, palatal defects, fused incisors, accessory oral frenula and tongue nodules, in association with brain anomalies that range from pituitary anomalies to alobar holoprosencephaly. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_005080* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR000571	Znf_CCCH	Domain
IPR003954	RRM_euk-type	Domain
IPR009145	U2AF_small	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF00642

UniProt features (18 total): compositionally biased region 7, region of interest 3, modified residue 2, cross-link 2, zinc finger region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15696-F1	69.72	0.31

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 (4): 349, 384, 45, 62

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway

MSigDB gene sets: 348 (showing top): TGACCTY_ERR1_Q2, MEF2_02, LHX3_01, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, TGANTCA_AP1_C, REACTOME_MRNA_SPLICING, BROWNE_HCMV_INFECTION_10HR_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, TAATTA_CHX10_01

GO Biological Process (4): spliceosomal complex assembly (GO:0000245), mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), mRNA processing (GO:0006397)

GO Molecular Function (7): zinc ion binding (GO:0008270), pre-mRNA 3’-splice site binding (GO:0030628), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U12-type spliceosomal complex (GO:0005689), U2AF complex (GO:0089701), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

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
binding	2
nuclear protein-containing complex	2
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
transition metal ion binding	1
pre-mRNA binding	1
protein binding	1
nucleic acid binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
ribonucleoprotein complex	1
spliceosomal complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZRSR2	U2AF2	P26368	969
ZRSR2	ASXL1	Q8IXJ9	825
ZRSR2	SETBP1	Q9Y6X0	778
ZRSR2	TET2	Q6N021	775
ZRSR2	STAG2	Q8N3U4	774
ZRSR2	PHF6	Q8IWS0	768
ZRSR2	SRSF2	Q01130	727
ZRSR2	DNMT3A	Q9Y6K1	720
ZRSR2	RUNX1	Q01196	719
ZRSR2	U2AF1	Q01081	715
ZRSR2	IDH1	O75874	698
ZRSR2	ETV6	P41212	698
ZRSR2	IDH2	P48735	697
ZRSR2	EZH2	Q15910	695
ZRSR2	SF3A1	Q15459	688

IntAct

95 interactions, top by confidence:

A	B	Type	Score
ZRSR2	SRPK2	psi-mi:“MI:0915”(physical association)	0.880
SRPK2	ZRSR2	psi-mi:“MI:0915”(physical association)	0.880
ZRSR2	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.880
ZRSR2	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	ZRSR2	psi-mi:“MI:0915”(physical association)	0.780
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
ZRSR2	ZRSR2P1	psi-mi:“MI:0915”(physical association)	0.740
ZRSR2P1	ZRSR2	psi-mi:“MI:0915”(physical association)	0.740
CCDC97	SF3B1	psi-mi:“MI:0914”(association)	0.730
ZRSR2	SF3B1	psi-mi:“MI:0914”(association)	0.730
ZRSR2	CLK2	psi-mi:“MI:0915”(physical association)	0.720
CLK2	ZRSR2	psi-mi:“MI:0915”(physical association)	0.720
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SRPK1	ZRSR2	psi-mi:“MI:0217”(phosphorylation reaction)	0.690
SSX2IP	ZRSR2	psi-mi:“MI:0915”(physical association)	0.670
ZRSR2	SSX2IP	psi-mi:“MI:0915”(physical association)	0.670
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
ZRSR2	TEPSIN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (161): ZRSR2 (Two-hybrid), ZRSR2 (Two-hybrid), SDCBP2 (Two-hybrid), SSX2IP (Two-hybrid), RPL26L1 (Affinity Capture-MS), PDCD7 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), RBM17 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), SRPK1 (Affinity Capture-MS), SRPK2 (Affinity Capture-MS), RPL10A (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SLC4A1AP (Affinity Capture-MS)

ESM2 similar proteins: A2AJT4, A2CG63, B0S733, F1QNX7, G3V8T1, O75376, O94988, P29536, Q02040, Q14241, Q149C2, Q15695, Q15696, Q28G87, Q2KIC0, Q4FZU3, Q4G0J3, Q4KKX4, Q4LE39, Q4R627, Q53F19, Q561R3, Q5NCR9, Q5R4U2, Q5RL73, Q5U2T3, Q5XIN3, Q5ZM19, Q60974, Q62377, Q63187, Q64707, Q6PFK1, Q6PGZ3, Q8BZR9, Q8C761, Q8CB77, Q8K2X2, Q8QG78, Q8TDR0

Diamond homologs: A1A4K8, O13845, Q01081, Q09176, Q15695, Q15696, Q29350, Q3T127, Q62377, Q64707, Q6AUG0, Q6YVX9, Q7TP17, Q8BGJ9, Q8WU68, Q94535, Q9D883, Q9FMY5, Q9S709, Q9SY74, Q9ZQW8, Q59LX5, Q8BGC0, O43719, Q5RB63, P90727, P90978, P97343, Q24562, Q5RCY1, Q63285, Q8TAS1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZRSR2	“form complex”	ZRSR2/U2AF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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
Metabolism of non-coding RNA	6	122.8×	6e-11
mRNA Splicing - Minor Pathway	9	65.0×	1e-13
snRNP Assembly	7	47.8×	1e-09
mRNA Splicing	13	46.0×	7e-18
SARS-CoV-2 modulates host translation machinery	6	43.3×	4e-08
mRNA Polyadenylation	15	42.5×	9e-20
CHD1 and CHD2 subfamily	12	42.1×	5e-16
Processing of Capped Intron-Containing Pre-mRNA	14	37.1×	7e-18

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	10	148.6×	4e-18
spliceosomal complex assembly	7	100.3×	2e-11
spliceosomal snRNP assembly	7	96.8×	2e-11
mRNA splicing, via spliceosome	14	30.5×	8e-16
RNA splicing	13	27.3×	4e-14
regulation of RNA splicing	5	26.1×	4e-05
mRNA processing	5	9.4×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	31
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
3062511	GRCh37/hg19 Xp22.33-11.1(chrX:168546-58364114)	Pathogenic
3341112	NM_005089.4(ZRSR2):c.868C>T (p.Arg290Ter)	Pathogenic
3367176	NM_005089.4(ZRSR2):c.1211_1212del (p.Gly404fs)	Pathogenic
3341117	NM_005089.4(ZRSR2):c.224G>A (p.Trp75Ter)	Likely pathogenic
3341118	NM_005089.4(ZRSR2):c.1120_1121dup (p.Ser375fs)	Likely pathogenic
4292589	NM_005089.4(ZRSR2):c.883C>T (p.Arg295Ter)	Likely pathogenic
978620	NM_005089.4(ZRSR2):c.1207_1208del (p.Arg403fs)	Likely pathogenic

SpliceAI

1888 predictions. Top by Δscore:

Variant	Effect	Δscore
X:15790533:CAAGG:C	donor_loss	1.0000
X:15790536:GGTA:G	donor_loss	1.0000
X:15790537:GTAA:G	donor_loss	1.0000
X:15790932:A:AG	acceptor_gain	1.0000
X:15790933:G:GG	acceptor_gain	1.0000
X:15790933:GCC:G	acceptor_gain	1.0000
X:15791010:TCAG:T	donor_loss	1.0000
X:15791011:CAGGT:C	donor_loss	1.0000
X:15791012:AGGT:A	donor_loss	1.0000
X:15791013:GGTGA:G	donor_loss	1.0000
X:15791014:GTG:G	donor_loss	1.0000
X:15791015:T:A	donor_loss	1.0000
X:15799870:A:AG	acceptor_gain	1.0000
X:15799870:AG:A	acceptor_gain	1.0000
X:15799871:G:GG	acceptor_gain	1.0000
X:15799871:GG:G	acceptor_gain	1.0000
X:15799871:GGACT:G	acceptor_gain	1.0000
X:15799949:GAGAG:G	donor_gain	1.0000
X:15799951:GAG:G	donor_gain	1.0000
X:15799952:AGG:A	donor_loss	1.0000
X:15799954:G:GA	donor_loss	1.0000
X:15803672:A:AG	acceptor_gain	1.0000
X:15803673:T:G	acceptor_gain	1.0000
X:15804107:A:AG	acceptor_gain	1.0000
X:15804108:A:G	acceptor_gain	1.0000
X:15804109:A:G	acceptor_gain	1.0000
X:15804110:GA:G	acceptor_gain	1.0000
X:15804195:G:GT	donor_gain	1.0000
X:15804247:G:GG	donor_gain	1.0000
X:15804781:G:GT	donor_gain	1.0000

AlphaMissense

3219 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:15809308:T:C	F183L	1.000
X:15809310:T:A	F183L	1.000
X:15809310:T:G	F183L	1.000
X:15818630:T:A	V272D	1.000
X:15820298:T:A	W307R	1.000
X:15820298:T:C	W307R	1.000
X:15820300:G:C	W307C	1.000
X:15820300:G:T	W307C	1.000
X:15820313:T:A	C312S	1.000
X:15820313:T:C	C312R	1.000
X:15820314:G:A	C312Y	1.000
X:15820314:G:C	C312S	1.000
X:15822775:T:C	F328L	1.000
X:15822777:T:A	F328L	1.000
X:15822777:T:G	F328L	1.000
X:15822781:C:G	H330D	1.000
X:15809275:T:C	C172R	0.999
X:15809281:T:C	F174L	0.999
X:15809283:C:A	F174L	0.999
X:15809283:C:G	F174L	0.999
X:15809292:A:C	K177N	0.999
X:15809292:A:T	K177N	0.999
X:15809302:T:A	C181S	0.999
X:15809302:T:C	C181R	0.999
X:15809303:G:A	C181Y	0.999
X:15809303:G:C	C181S	0.999
X:15809304:C:G	C181W	0.999
X:15815678:T:A	C187S	0.999
X:15815678:T:C	C187R	0.999
X:15815679:G:C	C187S	0.999

dbSNP variants (sampled 300 via entrez): RS1000336559 (X:15814845 A>G), RS1000501473 (X:15801478 G>A), RS1000546378 (X:15792844 T>C), RS1000573122 (X:15801188 C>T), RS1000674912 (X:15804368 G>A,C), RS1000695738 (X:15793612 C>G,T), RS1000724871 (X:15793053 T>C), RS1000726898 (X:15805321 C>T), RS1000962714 (X:15809904 G>A,C), RS1000998836 (X:15793285 AT>A,ATT), RS1001124804 (X:15819193 C>A,T), RS1001172790 (X:15805707 G>A), RS1001198211 (X:15788484 G>A), RS1001203863 (X:15805358 T>G), RS1001302314 (X:15816628 G>T)

Disease associations

OMIM: gene MIM:300028 | disease phenotypes: MIM:300868, MIM:301132, MIM:236100

GenCC curated gene-disease

Disease	Classification	Inheritance
orofaciodigital syndrome 21	Strong	X-linked

Mondo (3): multiple congenital anomalies-hypotonia-seizures syndrome 2 (MONDO:0010466), orofaciodigital syndrome 21 (MONDO:0975827), holoprosencephaly (MONDO:0016296)

Orphanet (2): Multiple congenital anomalies-hypotonia-seizures syndrome type 2 (Orphanet:300496), Holoprosencephaly (Orphanet:2162)

HPO phenotypes

91 total (30 of 91 shown, HPO-id order):

HPO	Term
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000085	Horseshoe kidney
HP:0000161	Median cleft upper lip
HP:0000180	Lobulated tongue
HP:0000189	Narrow palate
HP:0000191	Accessory oral frenulum
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000430	Underdeveloped nasal alae
HP:0000452	Choanal stenosis
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000568	Microphthalmia
HP:0000588	Optic disc coloboma
HP:0000677	Oligodontia
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000835	Adrenal hypoplasia
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001162	Postaxial hand polydactyly

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016142	Holoprosencephaly	C05.660.207.410; C10.500.034.875; C16.131.077.410; C16.131.260.380; C16.131.621.207.410; C16.131.666.034.875; C16.320.180.380

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
Irinotecan	affects cotreatment, increases response to substance	1
Temozolomide	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Leucovorin	affects cotreatment, increases response to substance	1
Ethyl Methanesulfonate	increases expression	1
Fluorouracil	affects cotreatment, increases response to substance	1
Hydrogen Peroxide	decreases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Theophylline	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00005016	Not specified	COMPLETED	Study of the Experiences and Needs of Parents Continuing a Pregnancy Following a Prenatal Diagnosis of Holopresencephaly
NCT00088426	Not specified	COMPLETED	Clinical and Genetic Studies on Holoprosencephaly
NCT00645645	Not specified	COMPLETED	A Study of the Genetic Analysis of Brain Disorders
NCT04691414	Not specified	COMPLETED	Retrospective Study Using Next Generation Sequencing (NGS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects.