ZRSR2

protein-coding

zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2, the group of U11/U12 di-snRNP|Zinc fingers CCCH-type|RNA binding motif containing

Gene 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 during spliceosome assembly. [provided by RefSeq, Jul 2008]

Previous symbols:

U2AF1L2

MANE transcript

NM_005089.4

Inheritance

ClinVar variants

P:6U:115B:8

Top phenotype

Orofaciodigital syndrome XXI

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:15,790,156-15,830,694

External References & Databases

Ensembl (ENSG00000169249)

Transcript & Mutation Effects

hg38 • Region Span ~40.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orofaciodigital syndrome 21STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0975827

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Orofaciodigital syndrome XXIXL

Manifestation: Craniofacial; Endocrine; Musculoskeletal; Neurologic

Intervention: Endocrine

Rationale: Early-onset endocrine abnormalities related to pituitary dysfunction have been described, and awareness may allow medical management

Refs: 38158857

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZRSR2 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 19

Orofaciodigital syndrome 21Total: 2

ZRSR2-related disorderTotal: 1

Abnormal heart morphologyTotal: 1

ZRSR2-related conditionTotal: 1

Severe hydrocephalusTotal: 1

Median cleft lip and palateTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005089.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	5 clinvar	1 clinvar	15
missense			64 clinvar	2 clinvar		66
nonsense	1 clinvar	2 clinvar	7 clinvar			10
start loss						0
frameshift	1 clinvar	2 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)			34 clinvar			34
Total	2	4	115	7	1	129

Highest pathogenic variant AF is 9.105387e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005089.4	RefSeq	NP_005080.1	11	MANE Select
ENST00000307771.8	Ensembl	ENSP00000303015.7	11	MANE Select
ENST00000380308.7	Ensembl	ENSP00000369664.3	4	Standard
ENST00000380308.8	Ensembl	ENSP00000369664.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of RNA
mRNA Splicing - Minor Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

spliceosomal complex assembly
mRNA splicing, via spliceosome
RNA splicing

Molecular Function

protein binding
pre-mRNA 3'-splice site binding
metal ion binding

Cellular Component

nucleoplasm
spliceosomal complex
U12-type spliceosomal complex
U2AF

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307771
Coding exons: 11
Length: 32789
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.46	137	194	0.706	0.0000168	3199
Missense (PolyPhen)		17	50.836	0.33441		845
Synonymous	0.276	64	66.9	0.957	0.00000526	820
Loss of Function	4.41	0	22.7	0.00	0.00000191	356

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 prespliceosome, a precursor to other spliceosomal complexes. For U2-type introns, it is selectively and specifically required for the second step of splicing. {ECO:0000269|PubMed:21041408, ECO:0000269|PubMed:9237760}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.144

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium