NFX1

protein-coding

nuclear transcription factor, X-box binding 1, the group of Ring finger proteins|PHD finger proteins

Gene summary

MHC class II gene expression is controlled primarily at the transcriptional level by transcription factors that bind to the X and Y boxes, two highly conserved elements in the proximal promoter of MHC class II genes. The protein encoded by this gene is a transcriptional repressor capable of binding to the conserved X box motif of HLA-DRA and other MHC class II genes in vitro. The protein may play a role in regulating the duration of an inflammatory response by limiting the period in which class II MHC molecules are induced by IFN-gamma. Three alternative splice variants, each of which encodes a different isoform, have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002504.6

Inheritance

—

ClinVar variants

U:141B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr9:33,290,512-33,371,157

External References & Databases

Ensembl (ENSG00000086102)

Transcript & Mutation Effects

hg38 • Region Span ~80.6 kb

Loading mutation effect viewer...

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 NFX1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002504.6. 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	2 clinvar		4
missense			131 clinvar	6 clinvar		137
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	141	8	0	149

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002504.6	RefSeq	NP_002495.2	24	MANE Select
ENST00000379540.8	Ensembl	ENSP00000368856.3	24	MANE Select
NM_001318758.2	RefSeq	NP_001305687.1	24	Standard
NM_147134.4	RefSeq	NP_667345.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Human papillomavirus infection - Homo sapiens (human)
Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation
Tryptophan degradation

Biological Process

negative regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
inflammatory response
viral process
negative regulation of MHC class II biosynthetic process

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
RNA binding

Cellular Component

nucleus
nucleolus
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379540
Coding exons: 24
Length: 80647
Individuals with no LoFs: 125701
Homozygous LoFs: 1
Heterozygous LoFs: 46
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	520	619	0.840	0.0000327	7415
Missense (PolyPhen)		116	181.35	0.63965		1967
Synonymous	0.665	206	219	0.943	0.0000120	2032
Loss of Function	4.99	19	61.1	0.311	0.00000337	756

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00016	0.00015	rare
South Asian	0.00026	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}.;

Intolerance Scores

LoFtool: 0.793
RVIS EVS: -1.59
RVIS percentile EVS: 3.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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