RFX2

protein-coding

regulatory factor X2, the group of Regulatory factor X family

Gene summary

This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. This protein can bind to cis elements in the promoter of the IL-5 receptor alpha gene. Two transcript variants encoding different isoforms have been described for this gene, and both variants utilize alternative polyadenylation sites. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000635.4

Inheritance

ClinVar variants

U:124B:10

Top phenotype

RFX2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr19:5,993,164-6,199,572

External References & Databases

Ensembl (ENSG00000087903)

Transcript & Mutation Effects

hg38 • Region Span ~206.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral palsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0006497

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RFX2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 121

not providedTotal: 2

RFX2-related disorderTotal: 2

Primary ciliary dyskinesiaTotal: 1

Tooth agenesisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000635.4. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			120 clinvar	7 clinvar		127
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	124	9	1	134

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000635.4	RefSeq	NP_000626.2	17	MANE Select
ENST00000303657.10	Ensembl	ENSP00000306335.4	17	MANE Select
NM_134433.3	RefSeq	NP_602309.1	16	Standard
ENST00000359161.7	Ensembl	ENSP00000352076.3	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rfx2	Danio rerio	Structure: liver Quality: symmetry abnormal

Gene / Model

Organism

Observed Phenotype

rfx2

Danio rerio

Structure: liver

Quality: symmetry

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

acrosome assembly
regulation of transcription by RNA polymerase II
spermatid development
positive regulation of transcription by RNA polymerase II
cilium assembly

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303657
Coding exons: 17
Length: 206409
Individuals with no LoFs: 125401
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125407
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.66	308	470	0.655	0.0000319	4669
Missense (PolyPhen)		83	158.87	0.52244		1543
Synonymous	1.06	198	218	0.908	0.0000175	1432
Loss of Function	5.13	3	36.5	0.0823	0.00000165	392

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00011	0.000087	rare
Ashkenazi Jewish	0.00011	0.00010	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor that acts as a key regulator of spermatogenesis. Acts by regulating expression of genes required for the haploid phase during spermiogenesis, such as genes required for cilium assembly and function (By similarity). Recognizes and binds the X-box, a regulatory motif with DNA sequence 5'-GTNRCC(0-3N)RGYAAC-3' present on promoters (PubMed:10330134). Probably activates transcription of the testis- specific histone gene HIST1H1T (By similarity). {ECO:0000250|UniProtKB:P48379, ECO:0000269|PubMed:10330134}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.177
RVIS EVS: -0.86
RVIS percentile EVS: 10.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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