CELF4

protein-coding

CUGBP Elav-like family member 4, the group of RNA binding motif containing

Gene summary

Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

BRUNOL4

MANE transcript

NM_020180.4

Inheritance

ClinVar variants

P:3U:82B:21

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr18:37,243,040-37,565,827

External References & Databases

Ensembl (ENSG00000101489)

Transcript & Mutation Effects

hg38 • Region Span ~322.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CELF4 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 32

Neurodevelopmental disorderTotal: 13

CELF4-related disorderTotal: 12

Myoepithelial tumorTotal: 1

Inborn genetic diseasesTotal: 1

Developmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020180.4. 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				10 clinvar	2 clinvar	12
missense			67 clinvar	8 clinvar	1 clinvar	76
nonsense	1 clinvar	1 clinvar	6 clinvar			8
start loss						0
frameshift		1 clinvar	5 clinvar			6
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	2	82	18	3	106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 190 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020180.4	RefSeq	NP_064565.1	12	MANE Select
ENST00000420428.7	Ensembl	ENSP00000410584.2	12	MANE Select
NM_001025087.2	RefSeq	NP_001020258.1	12	Standard
NM_001025088.2	RefSeq	NP_001020259.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA Processing

Biological Process

alternative mRNA splicing, via spliceosome
regulation of alternative mRNA splicing, via spliceosome
mRNA splice site selection
germ cell development
embryo development ending in birth or egg hatching

Molecular Function

translation repressor activity, mRNA regulatory element binding
RNA binding
mRNA binding
pre-mRNA binding
BRE binding

Cellular Component

nucleus
cytoplasm
ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000420428
Coding exons: 12
Length: 322991
Individuals with no LoFs: 125593
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125598
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.16	157	315	0.499	0.0000179	3208
Missense (PolyPhen)		59	152.94	0.38578		1558
Synonymous	1.05	116	131	0.884	0.00000891	903
Loss of Function	4.48	2	27.2	0.0735	0.00000154	266

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00013	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000021	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: RNA-binding protein implicated in the regulation of pre- mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Promotes exclusion of both the smooth muscle (SM) and non-muscle (NM) exons in actinin pre-mRNAs. Activates the splicing of MAPT/Tau exon 10. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA. {ECO:0000269|PubMed:11158314, ECO:0000269|PubMed:12649496, ECO:0000269|PubMed:14973222, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:15894795}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.344
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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