UFL1

protein-coding

UFM1 specific ligase 1

Gene summary

Enables UFM1 ligase activity and protein kinase binding activity. Involved in several processes, including positive regulation of reticulophagy; regulation of intracellular signal transduction; and regulation of protein metabolic process. Acts upstream of or within several processes, including positive regulation of cell population proliferation; regulation of proteasomal ubiquitin-dependent protein catabolic process; and response to endoplasmic reticulum stress. Located in cytoplasm; nucleus; and site of double-strand break. Part of protein-containing complex. Is active in endoplasmic reticulum membrane and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA0776

MANE transcript

NM_015323.5

Inheritance

—

ClinVar variants

U:127B:4

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr6:96,521,595-96,555,276

External References & Databases

Ensembl (ENSG00000014123)

Transcript & Mutation Effects

hg38 • Region Span ~33.7 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 UFL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 4

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015323.5. 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			5 clinvar		1 clinvar	6
missense			118 clinvar	1 clinvar	2 clinvar	121
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	127	1	3	131

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015323.5	RefSeq	NP_056138.1	19	MANE Select
ENST00000369278.5	Ensembl	ENSP00000358283.4	19	MANE Select
ENST00000863355.1	Ensembl	ENSP00000533414.1	19	Standard
ENST00000863355.2	Ensembl	ENSP00000533414.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

osteoblast differentiation
positive regulation of cell population proliferation
negative regulation of protein ubiquitination
negative regulation of NF-kappaB transcription factor activity
regulation of proteasomal ubiquitin-dependent protein catabolic process

Molecular Function

protein binding
UFM1 transferase activity

Cellular Component

cytoplasm
endoplasmic reticulum
endoplasmic reticulum membrane
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369278
Coding exons: 19
Length: 33682
Individuals with no LoFs: 125625
Homozygous LoFs: 0
Heterozygous LoFs: 123
Defined: 125748
p: 0.000489

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.189	393	404	0.974	0.0000202	5193
Missense (PolyPhen)		87	102.34	0.85011		1336
Synonymous	-0.0426	143	142	1.00	0.00000711	1476
Loss of Function	2.38	26	42.8	0.608	0.00000227	538

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00057	0.00055	rare
Latino/Admixed American	0.00046	0.00043	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00046	0.00044	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00067	0.00064	rare
South Asian	0.00038	0.00036	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, a post-translational modification on lysine residues of proteins that may play a crucial role in a number of cellular processes. Mediates DDRGK1 ufmylation and may regulate the proteasomal degradation of DDRGK1 and CDK5RAP3 thereby modulating NF-kappa-B signaling (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498). May also through TRIP4 ufmylation play a role in nuclear receptors-mediated transcription (PubMed:25219498). May play a role in the unfolded protein response, mediating the ufmylation of multiple proteins in response to endoplasmic reticulum stress (PubMed:23152784). {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180, ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:23152784, ECO:0000269|PubMed:25219498}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

RVIS EVS: -0.78
RVIS percentile EVS: 13.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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