NFXL1

protein-coding

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

Gene summary

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of DNA-templated transcription. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001278624.2

Inheritance

—

ClinVar variants

P:1U:130B:9

Top phenotype

NFXL1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr4:47,847,233-47,914,667

External References & Databases

Ensembl (ENSG00000170448)

Transcript & Mutation Effects

hg38 • Region Span ~67.4 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 NFXL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 123

NFXL1-related disorderTotal: 11

Structural heart defects and renal anomalies syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001278624.2. 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	1 clinvar	1 clinvar	3
missense			125 clinvar	3 clinvar	4 clinvar	132
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	130	4	5	140

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001278624.2	RefSeq	NP_001265553.1	22	MANE Select
ENST00000507489.2	Ensembl	ENSP00000422037.1	22	MANE Select
NM_001278623.1	RefSeq	NP_001265552.1	22	Standard
NM_152995.6	RefSeq	NP_694540.3	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II

Molecular Function

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

Cellular Component

nucleus
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000507489
Coding exons: 22
Length: 67397
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125747
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.39	399	485	0.822	0.0000243	5939
Missense (PolyPhen)		92	162.12	0.5675		1844
Synonymous	0.488	148	156	0.950	0.00000744	1642
Loss of Function	4.51	19	55.1	0.345	0.00000312	685

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00010	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0799

Intolerance Scores

LoFtool: 0.643
RVIS EVS: 0.22
RVIS percentile EVS: 68.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.294

Gene Damage Prediction

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