RFX1

protein-coding

regulatory factor X1, the group of Regulatory factor X family

Gene summary

This gene encodes a member of the regulatory factor X (RFX) family of transcription factors, which are characterized by a winged-helix DNA-binding domain. The encoded transcription factor contains an N-terminal activation domain and a C-terminal repression domain, and may activate or repress target gene expression depending on cellular context. This transcription factor has been shown to regulate a wide variety of genes involved in immunity and cancer, including the MHC class II genes and genes that may be involved in cancer progression. This gene exhibits altered expression in glioblastoma and the autoimmune disease systemic lupus erythematosis (SLE). [provided by RefSeq, Jul 2016]

MANE transcript

NM_002918.5

Inheritance

—

ClinVar variants

U:139B:17

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr19:13,961,530-14,007,039

External References & Databases

Ensembl (ENSG00000132005)

Transcript & Mutation Effects

hg38 • Region Span ~45.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RFX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 134

not providedTotal: 14

Abnormality of neuronal migrationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002918.5. 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			2 clinvar	1 clinvar	7 clinvar	10
missense			133 clinvar	4 clinvar	5 clinvar	142
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	139	5	12	156

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002918.5	RefSeq	NP_002909.4	20	MANE Select
ENST00000254325.9	Ensembl	ENSP00000254325.3	20	MANE Select
ENST00000588885.1	Ensembl	ENSP00000464960.1	3	Standard
ENST00000872111.1	Ensembl	ENSP00000542170.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
immune response

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254325
Coding exons: 20
Length: 45502
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125684
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.69	431	620	0.696	0.0000432	6197
Missense (PolyPhen)		89	202.54	0.43943		1928
Synonymous	0.623	285	299	0.954	0.0000249	2027
Loss of Function	5.50	7	48.2	0.145	0.00000225	510

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000065	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00036	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory factor essential for MHC class II genes expression. Binds to the X boxes of MHC class II genes. Also binds to an inverted repeat (ENH1) required for hepatitis B virus genes expression and to the most upstream element (alpha) of the RPL30 promoter.;

Recessive Scores

pRec: 0.194

Intolerance Scores

LoFtool: 0.0450
RVIS EVS: -0.08
RVIS percentile EVS: 47.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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