RLF

protein-coding

RLF zinc finger, the group of Zinc fingers C2H2-type

Gene summary

Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of heterochromatin formation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_012421.4

Inheritance

—

ClinVar variants

U:186B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr1:40,161,387-40,240,921

External References & Databases

Ensembl (ENSG00000117000)

Transcript & Mutation Effects

hg38 • Region Span ~79.5 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 RLF variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 188

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012421.4. 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				3 clinvar	3 clinvar	6
missense			185 clinvar	4 clinvar	3 clinvar	192
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	186	7	6	199

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012421.4	RefSeq	NP_036553.2	8	MANE Select
ENST00000372771.5	Ensembl	ENSP00000361857.4	8	MANE Select
ENST00000989474.1	Ensembl	ENSP00000659291.1	2	Standard
ENST00000989475.1	Ensembl	ENSP00000659292.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
DNA integration
regulation of DNA methylation
positive regulation of transcription, DNA-templated
positive regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein binding
zinc ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372771
Coding exons: 8
Length: 79549
Individuals with no LoFs: 125122
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125123
p: 0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.46	669	973	0.688	0.0000471	12682
Missense (PolyPhen)		107	321.14	0.33319		4151
Synonymous	-0.225	358	353	1.02	0.0000167	3482
Loss of Function	7.93	0	73.2	0.00	0.00000402	1024

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	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.00696
RVIS EVS: 0.08
RVIS percentile EVS: 59.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.941

Gene Damage Prediction

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