CSTF2

protein-coding

cleavage stimulation factor subunit 2, the group of RNA binding motif containing|Cleavage stimulation factor subunits

Gene summary

This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001325.3

Inheritance

ClinVar variants

P:1U:102B:5

Top phenotype

Intellectual developmental disorder, X-linked 113

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:100,820,391-100,841,520

External References & Databases

Ensembl (ENSG00000101811)

Transcript & Mutation Effects

hg38 • Region Span ~21.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, X-linked 113LIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0958200

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked 113XL

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 32816001

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSTF2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 9

Intellectual developmental disorder, X-linked 113Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001325.3. 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			10 clinvar	1 clinvar	1 clinvar	12
missense	1 clinvar		68 clinvar	3 clinvar		72
nonsense			8 clinvar			8
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			16 clinvar			16
Total	1	0	102	4	1	108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001325.3	RefSeq	NP_001316.1	13	MANE Select
ENST00000372972.7	Ensembl	ENSP00000362063.2	13	MANE Select
NM_001306206.2	RefSeq	NP_001293135.1	14	Standard
NM_001306209.2	RefSeq	NP_001293138.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA surveillance pathway - Homo sapiens (human)
mRNA Processing
tRNA processing
Gene expression (Transcription)
polyadenylation of mrna

Biological Process

mRNA splicing, via spliceosome
termination of RNA polymerase II transcription
mRNA polyadenylation
mRNA 3'-end processing
pre-mRNA cleavage required for polyadenylation

Molecular Function

RNA binding
mRNA binding
protein binding

Cellular Component

nucleoplasm
mRNA cleavage and polyadenylation specificity factor complex
nuclear body
cleavage body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372972
Coding exons: 13
Length: 20538
Individuals with no LoFs: 116298
Homozygous LoFs: 1
Heterozygous LoFs: 0
Defined: 116299
p: 0.00000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.43	88	236	0.372	0.0000181	3723
Missense (PolyPhen)		28	107.95	0.25938		1740
Synonymous	1.09	67	79.3	0.845	0.00000599	1191
Loss of Function	4.39	0	22.4	0.00	0.00000190	339

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)	0.000013	0.0000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs (By similarity). {ECO:0000250, ECO:0000269|PubMed:9199325}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.497
RVIS EVS: 0.24
RVIS percentile EVS: 68.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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