ZRSR2 (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2)

Gene

• Entrez ID: 8233
• Gene name: Zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2
• Gene symbol: ZRSR2
• Synonyms (NCBI Gene): OFD21, U2AF1-RS2, U2AF1L2, U2AF1RS2, URP, ZC3H22
• Chromosome: X
• Chromosome location: Xp22.2
• Summary: 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

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000245	Process	Spliceosomal complex assembly	IMP	21041408
GO:0000398	Process	MRNA splicing, via spliceosome	IBA
GO:0000398	Process	MRNA splicing, via spliceosome	IEA
GO:0000398	Process	MRNA splicing, via spliceosome	IMP	9237760
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003723	Function	RNA binding	IEA
GO:0005515	Function	Protein binding	IPI	9237760, 23602568, 25416956, 28514442, 31515488, 32296183, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005681	Component	Spliceosomal complex	IBA
GO:0005681	Component	Spliceosomal complex	IEA
GO:0005689	Component	U12-type spliceosomal complex	IDA	15146077, 21041408
GO:0006397	Process	MRNA processing	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0008380	Process	RNA splicing	IC	15146077
GO:0008380	Process	RNA splicing	IEA
GO:0030628	Function	Pre-mRNA 3'-splice site binding	IBA
GO:0030628	Function	Pre-mRNA 3'-splice site binding	IDA	21041408
GO:0042802	Function	Identical protein binding	IPI	32296183
GO:0046872	Function	Metal ion binding	IEA
GO:0089701	Component	U2AF complex	IBA
GO:0089701	Component	U2AF complex	IEA
GO:1990904	Component	Ribonucleoprotein complex	IEA

Other IDs

• MIM: 300028
• HGNC: 23019
• e!Ensembl: ENSG00000169249

Protein

• UniProt ID: Q15696
• Protein name: U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 (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) (
• Protein 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 i
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00642	zf-CCCH	167 → 193	Zinc finger C-x8-C-x5-C-x3-H type (and similar)	Family
  PF00076	RRM_1	240 → 298	RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain)	Domain
  PF00642	zf-CCCH	307 → 332	Zinc finger C-x8-C-x5-C-x3-H type (and similar)	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9237760}.
• Sequence:

  MAAPEKMTFPEKPSHKKYRAALKKEKRKKRRQELARLRDSGLSQKEEEEDTFIEEQQLEE
  EKLLERERQRLHEEWLLREQKAQEEFRIKKEKEEAAKKRQEEQERKLKEQWEEQQRKERE
  EEEQKRQEKKEKEEALQKMLDQAENELENGTTWQNPEPPVDFRVMEKDRANCPFYSKTGA
  CRFGDRCSRKHNFPTSSPTLLIKSMFTTFGMEQCRRDDYDPDASLEYSEEETYQQFLDFY
  EDVLPEFKNVGKVIQFKVSCNLEPHLRGNVYVQYQSEEECQAALSLFNGRWYAGRQLQCE
  FCPVTRWKMAICGLFEIQQCPRGKHCNFLHVFRNPNNEFWEANRDIYLSPDRTGSSFGKN
  SERRERMGHHDDYYSRLRGRRNPSPDHSYKRNGESERKSSRHRGKKSHKRTSKSRERHNS
  RSRGRNRDRSRDRSRGRGSRSRSRSRSRRSRRSRSQSSSRSRSRGRRRSGNRDRTVQSPK
  SK

• Sequence length: 482

Pathways

Reactome:

mRNA Splicing - Minor Pathway

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Heart, malformation of	Likely pathogenic	rs1933151965	RCV001257352	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Holoprosencephaly sequence	Likely pathogenic	rs1933151965	RCV001257352	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Median cleft lip and palate	Likely pathogenic	rs1933151965	RCV001257352	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Orofaciodigital syndrome 21	Likely pathogenic	rs1933151965	RCV004771808	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe hydrocephalus	Likely pathogenic	rs1933151965	RCV001257352	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONGENITAL HEART DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HOLOPROSENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYELODYSPLASTIC SYNDROMES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIODIGITAL SYNDROME XXI	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute leukemia	Leukemia	BEFREE	28942350		★☆☆☆☆ Found in Text Mining only
Anemia Macrocytic	Macrocytic anemia	Pubtator	35351745	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Macrocytic	Anemia	BEFREE	28942350		★☆☆☆☆ Found in Text Mining only
Arnold Chiari Malformation	Arnold-Chiari malformation	BEFREE	30621833		★☆☆☆☆ Found in Text Mining only
Behcet Syndrome	Behcet disease	Pubtator	35351745	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	CGI_DG			★☆☆☆☆ Found in Text Mining only
Disseminated Intravascular Coagulation	Disseminated intravascular coagulation	Pubtator	40066790	Associate	★☆☆☆☆ Found in Text Mining only
Hematoma	Hematoma	Pubtator	40066790	Associate	★☆☆☆☆ Found in Text Mining only
Hypergammaglobulinemia	Hypergammaglobulinemia	Pubtator	36445600	Associate	★☆☆☆☆ Found in Text Mining only
Juvenile Myelomonocytic Leukemia	Myelomonocytic Leukemia	CTD_human_DG	26457647		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	34615655	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid	Myeloid leukemia	Pubtator	28545085, 37427790	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	22343920, 25550361, 27992414, 32112433, 32380535, 33885753, 37441846, 37766563, 38636413	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myelomonocytic Chronic	Myelomonocytic leukemia	Pubtator	29069007	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	23645565		★☆☆☆☆ Found in Text Mining only
Leukopenia	Leukopenia	BEFREE	28942350		★☆☆☆☆ Found in Text Mining only
Myelodysplasia	Myelodysplasia	BEFREE	24903747		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	22389253, 23645565, 24903747, 25586593, 25645650, 25964599, 31124956, 31680297		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	CTD_human_DG	27992414		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	CGI_DG			★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	22343920, 22389253, 23300180, 27992414, 28242684, 31680297, 32380535, 32781289, 36109871, 36216757, 37766563	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neoplasms	Neoplasms	BEFREE	27256388		★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	BEFREE	22343920		★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	Pubtator	22343920	Associate	★☆☆☆☆ Found in Text Mining only
Orofaciodigital Syndromes	Orofaciodigital syndrome	Pubtator	38158857	Associate	★☆☆☆☆ Found in Text Mining only
Thrombocytopenia	Thrombocytopenia	Pubtator	22343920	Associate	★☆☆☆☆ Found in Text Mining only